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Hypertriglyceridemia

MedGen UID:
167238
Concept ID:
C0813230
Finding
Synonym: Hypertriglyceridaemia
SNOMED CT: Serum triglycerides raised (166848004); Serum triglycerides above reference range (166848004)
 
HPO: HP:0002155
Monarch Initiative: MONDO:0005347

Definition

An abnormal increase in the level of triglycerides in the blood. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHypertriglyceridemia

Conditions with this feature

Cholesteryl ester storage disease
MedGen UID:
40266
Concept ID:
C0008384
Disease or Syndrome
Deficiency of lysosomal acid lipase causes 2 distinct phenotypes in humans: Wolman disease (WOLD; 620151) and cholesteryl ester storage disease (CESD). WOLD is an early-onset fulminant disorder of infancy with massive infiltration of the liver, spleen, and other organs by macrophages filled with cholesteryl esters and triglycerides. Death occurs early in life. CESD is a milder, later-onset disorder with primary hepatic involvement by macrophages engorged with cholesteryl esters. This slowly progressive visceral disease has a wide spectrum of involvement ranging from early onset with severe cirrhosis to later onset of more slowly progressive hepatic disease with survival into adulthood (summary by Du et al., 2001).
Glycogen storage disease, type VI
MedGen UID:
6643
Concept ID:
C0017925
Disease or Syndrome
Glycogen storage disease type VI (GSD VI) is a disorder of glycogenolysis caused by deficiency of hepatic glycogen phosphorylase. This critical enzyme catalyzes the rate-limiting step in glycogen degradation, and deficiency of the enzyme in the untreated child is characterized by hepatomegaly, poor growth, ketotic hypoglycemia, elevated hepatic transaminases, hyperlipidemia, and low prealbumin level. GSD VI is usually a relatively mild disorder that presents in infancy and childhood; rare cases of more severe disease manifesting with recurrent hypoglycemia and marked hepatomegaly have been described. More common complications in the setting of suboptimal metabolic control include short stature, delayed puberty, osteopenia, and osteoporosis. Hepatic fibrosis commonly develops in GSD VI, but cirrhosis and hypertrophic cardiomyopathy are rare. Clinical and biochemical abnormalities may decrease with age, but ketosis and hypoglycemia can continue to occur.
Norum disease
MedGen UID:
9698
Concept ID:
C0023195
Disease or Syndrome
Complete LCAT deficiency is a disorder that primarily affects the eyes and kidneys.\n\nIn complete LCAT deficiency, the clear front surface of the eyes (the corneas) gradually becomes cloudy. The cloudiness, which generally first appears in early childhood, consists of small grayish dots of cholesterol (opacities) distributed across the corneas. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals; it aids in many functions of the body but can become harmful in excessive amounts. As complete LCAT deficiency progresses, the corneal cloudiness worsens and can lead to severely impaired vision.\n\nPeople with complete LCAT deficiency often have kidney disease that begins in adolescence or early adulthood. The kidney problems get worse over time and may eventually lead to kidney failure. Individuals with this disorder also usually have a condition known as hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Anemia can cause pale skin, weakness, fatigue, and more serious complications.\n\nOther features of complete LCAT deficiency that occur in some affected individuals include enlargement of the liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy) or an accumulation of fatty deposits on the artery walls (atherosclerosis).
Prader-Willi syndrome
MedGen UID:
46057
Concept ID:
C0032897
Disease or Syndrome
Prader-Willi syndrome (PWS) is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity (unless eating is externally controlled). Motor milestones and language development are delayed. All individuals have some degree of cognitive impairment. A distinctive behavioral phenotype (with temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive characteristics) is common. Hypogonadism is present in both males and females and manifests as genital hypoplasia, incomplete pubertal development, and, in most, infertility. Short stature is common (if not treated with growth hormone); characteristic facial features, strabismus, and scoliosis are often present.
Tangier disease
MedGen UID:
52644
Concept ID:
C0039292
Disease or Syndrome
Tangier disease is characterized by severe deficiency or absence of high-density lipoprotein (HDL) in the circulation resulting in tissue accumulation of cholesteryl esters throughout the body, particularly in the reticuloendothelial system. The major clinical signs of Tangier disease include hyperplastic yellow-orange tonsils, hepatosplenomegaly, and peripheral neuropathy, which may be either relapsing-remitting or chronic progressive in nature. Rarer complications may include corneal opacities that typically do not affect vision, premature atherosclerotic coronary artery disease occurring in the sixth and seventh decades of life (not usually before age 40 years), and mild hematologic manifestations, such as mild thrombocytopenia, reticulocytosis, stomatocytosis, or hemolytic anemia. The clinical expression of Tangier disease is variable, with some affected individuals only showing biochemical perturbations.
Werner syndrome
MedGen UID:
12147
Concept ID:
C0043119
Disease or Syndrome
Werner syndrome is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Individuals with Werner syndrome develop normally until the end of the first decade. The first sign is the lack of a growth spurt during the early teen years. Early findings (usually observed in the 20s) include loss and graying of hair, hoarseness, and scleroderma-like skin changes, followed by bilateral ocular cataracts, type 2 diabetes mellitus, hypogonadism, skin ulcers, and osteoporosis in the 30s. Myocardial infarction and cancer are the most common causes of death; the mean age of death in individuals with Werner syndrome is 54 years.
Niemann-Pick disease, type B
MedGen UID:
78651
Concept ID:
C0268243
Disease or Syndrome
The phenotype of acid sphingomyelinase deficiency (ASMD) occurs along a continuum. Individuals with the severe early-onset form, infantile neurovisceral ASMD, were historically diagnosed with Niemann-Pick disease type A (NPD-A). The later-onset, chronic visceral form of ASMD is also referred to as Niemann-Pick disease type B (NPD-B). A phenotype with intermediate severity is also known as chronic neurovisceral ASMD (NPD-A/B). The most common presenting symptom in NPD-A is hepatosplenomegaly, usually detectable by age three months; over time the liver and spleen become massive in size. Psychomotor development progresses no further than the 12-month level, after which neurologic deterioration is relentless. Failure to thrive typically becomes evident by the second year of life. A classic cherry-red spot of the macula of the retina, which may not be present in the first few months, is eventually present in all affected children. Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. Most children succumb before the third year of life. NPD-B generally presents later than NPD-A, and the manifestations are less severe. NPD-B is characterized by progressive hepatosplenomegaly, gradual deterioration in liver and pulmonary function, osteopenia, and atherogenic lipid profile. No central nervous system (CNS) manifestations occur. Individuals with NPD-A/B have symptoms that are intermediate between NPD-A and NPD-B. The presentation in individuals with NPD-A/B varies greatly, although all are characterized by the presence of some CNS manifestations. Survival to adulthood can occur in individuals with NPD-B and NPD-A/B.
Inborn glycerol kinase deficiency
MedGen UID:
82803
Concept ID:
C0268418
Disease or Syndrome
NR0B1-related adrenal hypoplasia congenita includes both X-linked adrenal hypoplasia congenita (X-linked AHC) and Xp21 deletion (previously called complex glycerol kinase deficiency). X-linked AHC is characterized by primary adrenal insufficiency and/or hypogonadotropic hypogonadism (HH). Adrenal insufficiency is acute infantile onset (average age 3 weeks) in approximately 60% of affected males and childhood onset (ages 1-9 years) in approximately 40%. HH typically manifests in a male with adrenal insufficiency as delayed puberty (i.e., onset age >14 years) and less commonly as arrested puberty at about Tanner Stage 3. Rarely, X-linked AHC manifests initially in early adulthood as delayed-onset adrenal insufficiency, partial HH, and/or infertility. Heterozygous females very occasionally have manifestations of adrenal insufficiency or hypogonadotropic hypogonadism. Xp21 deletion includes deletion of NR0B1 (causing X-linked AHC) and GK (causing glycerol kinase deficiency), and in some cases deletion of DMD (causing Duchenne muscular dystrophy). Developmental delay has been reported in males with Xp21 deletion when the deletion extends proximally to include DMD or when larger deletions extend distally to include IL1RAPL1 and DMD.
Alstrom syndrome
MedGen UID:
78675
Concept ID:
C0268425
Disease or Syndrome
Alström syndrome is characterized by cone-rod dystrophy, obesity, progressive bilateral sensorineural hearing impairment, acute infantile-onset cardiomyopathy and/or adolescent- or adult-onset restrictive cardiomyopathy, insulin resistance / type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), and chronic progressive kidney disease. Cone-rod dystrophy presents as progressive visual impairment, photophobia, and nystagmus usually starting between birth and age 15 months. Many individuals lose all perception of light by the end of the second decade, but a minority retain the ability to read large print into the third decade. Children usually have normal birth weight but develop truncal obesity during their first year. Sensorineural hearing loss presents in the first decade in as many as 70% of individuals and may progress to the severe or moderately severe range (40-70 db) by the end of the first to second decade. Insulin resistance is typically accompanied by the skin changes of acanthosis nigricans, and proceeds to T2DM in the majority by the third decade. Nearly all demonstrate hypertriglyceridemia. Other findings can include endocrine abnormalities (hypothyroidism, hypogonadotropic hypogonadism in males, and hyperandrogenism in females), urologic dysfunction / detrusor instability, progressive decrease in renal function, and hepatic disease (ranging from elevated transaminases to steatohepatitis/NAFLD). Approximately 20% of affected individuals have delay in early developmental milestones, most commonly in gross and fine motor skills. About 30% have a learning disability. Cognitive impairment (IQ <70) is very rare. Wide clinical variability is observed among affected individuals, even within the same family.
Fish-eye disease
MedGen UID:
83354
Concept ID:
C0342895
Disease or Syndrome
Fish eye disease (FED) is a rare familial disorder characterized by severe high-density lipoprotein (HDL) deficiency and massive corneal opacities (summary by Kastelein et al., 1992).
Neonatal pseudo-hydrocephalic progeroid syndrome
MedGen UID:
140806
Concept ID:
C0406586
Disease or Syndrome
Wiedemann-Rautenstrauch syndrome (WDRTS) is a rare autosomal recessive neonatal progeroid disorder characterized by intrauterine growth retardation, failure to thrive, short stature, a progeroid appearance, hypotonia, and variable mental impairment (summary by Toriello, 1990). Average survival in WDRTS is 7 months, although survival into the third decade of life has been reported (Akawi et al., 2013).
Subcutaneous panniculitis-like T-cell lymphoma
MedGen UID:
99306
Concept ID:
C0522624
Neoplastic Process
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon form of T-cell non-Hodgkin lymphoma in which cytotoxic CD8 (see 186910)+ T cells infiltrate adipose tissue forming subcutaneous nodules. Both children and adults can be affected, with a median age at diagnosis of 36 years and a female gender bias. Most patients have accompanying systemic features such as fever or flank pain. A subset (about 20%) of patients develop hemophagocytic lymphohistiocytosis (HLH), usually associated with CD8+ T cells rimming adipocytes in the bone marrow. An infectious agent is not identified, and the disorder is believed to result from improperly activated inflammation. Immunosuppressive therapy may be helpful; hematopoietic bone marrow transplantation is usually curative (summary by Gayden et al., 2018). For a general discussion of genetic heterogeneity of HLH, see HLH1 (267700).
Smith-Magenis syndrome
MedGen UID:
162881
Concept ID:
C0795864
Disease or Syndrome
Smith-Magenis syndrome (SMS) is characterized by distinctive physical features (particularly coarse facial features that progress with age), developmental delay, cognitive impairment, behavioral abnormalities, sleep disturbance, and childhood-onset abdominal obesity. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping or need to be awakened for feeds, and generalized lethargy. The majority of individuals function in the mild-to-moderate range of intellectual disability. The behavioral phenotype, including significant sleep disturbance, stereotypies, and maladaptive and self-injurious behaviors, is generally not recognized until age 18 months or older and continues to change until adulthood. Sensory issues are frequently noted; these may include avoidant behavior, as well as repetitive seeking of textures, sounds, and experiences. Toileting difficulties are common. Significant anxiety is common as are problems with executive functioning, including inattention, distractibility, hyperactivity, and impulsivity. Maladaptive behaviors include frequent outbursts / temper tantrums, attention-seeking behaviors, opposition, aggression, and self-injurious behaviors including self-hitting, self-biting, skin picking, inserting foreign objects into body orifices (polyembolokoilamania), and yanking fingernails and/or toenails (onychotillomania). Among the stereotypic behaviors described, the spasmodic upper-body squeeze or "self-hug" seems to be highly associated with SMS. An underlying developmental asynchrony, specifically emotional maturity delayed beyond intellectual functioning, may also contribute to maladaptive behaviors in people with SMS.
Atherogenic lipoprotein phenotype
MedGen UID:
283903
Concept ID:
C1531719
Finding
The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a preponderance of small, dense low density lipoprotein (LDL) particles (subclass pattern B), increased levels of triglyceride-rich lipoproteins, reduction in high density lipoprotein, and a 3-fold increased risk of myocardial infarction (summary by Nishina et al., 1992). The so-called atherogenic lipoprotein phenotype was shown by Austin et al. (1988) to be independently associated with an increased risk for coronary artery disease. Allayee et al. (1998) concluded, furthermore, that there is a genetically based association between familial combined hyperlipidemia (FCHL; 144250) and small, dense LDL particles and that the genetic determinants for LDL particle size are shared, at least in part, among FCHL families and the more general population at risk for coronary artery disease. Juo et al. (1998) concluded from a bivariate segregation analysis of small, dense LDL particles and elevated apolipoprotein B levels (APOB; 107730), which are commonly found together in members of FCHL families, that the 2 traits share a common major gene plus individual polygenic components. The common major gene was estimated to explain 37% of the variance of adjusted LDL particle size and 23% of the variance of adjusted apoB levels.
Familial apolipoprotein C-II deficiency
MedGen UID:
328375
Concept ID:
C1720779
Disease or Syndrome
Clinically and biochemically, apoC-II deficiency closely simulates lipoprotein lipase deficiency, or hyperlipoproteinemia type I (238600), and is therefore referred to as hyperlipoproteinemia type IB.
Familial partial lipodystrophy, Kobberling type
MedGen UID:
318591
Concept ID:
C1720859
Disease or Syndrome
Familial partial lipodystrophy type 1 (FPLD1), or Kobberling-type lipodystrophy, is characterized by loss of adipose tissue confined to the extremities, with normal or increased distribution of fat on the face, neck, and trunk (Kobberling and Dunnigan, 1986). For a general description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.
Familial partial lipodystrophy, Dunnigan type
MedGen UID:
354526
Concept ID:
C1720860
Disease or Syndrome
Familial partial lipodystrophy is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution beginning in late childhood or early adult life. Affected individuals gradually lose fat from the upper and lower extremities and the gluteal and truncal regions, resulting in a muscular appearance with prominent superficial veins. In some patients, adipose tissue accumulates on the face and neck, causing a double chin, fat neck, or cushingoid appearance. Metabolic abnormalities include insulin-resistant diabetes mellitus with acanthosis nigricans and hypertriglyceridemia; hirsutism and menstrual abnormalities occur infrequently. Familial partial lipodystrophy may also be referred to as lipoatrophic diabetes mellitus, but the essential feature is loss of subcutaneous fat (review by Garg, 2004). The disorder may be misdiagnosed as Cushing disease (see 219080) (Kobberling and Dunnigan, 1986; Garg, 2004). Genetic Heterogeneity of Familial Partial Lipodystrophy Familial partial lipodystrophy is a clinically and genetically heterogeneous disorder. Types 1 and 2 were originally described as clinical subtypes: type 1 (FPLD1; 608600), characterized by loss of subcutaneous fat confined to the limbs (Kobberling et al., 1975), and FPLD2, characterized by loss of subcutaneous fat from the limbs and trunk (Dunnigan et al., 1974; Kobberling and Dunnigan, 1986). No genetic basis for FPLD1 has yet been delineated. FPLD3 (604367) is caused by mutation in the PPARG gene (601487) on chromosome 3p25; FPLD4 (613877) is caused by mutation in the PLIN1 gene (170290) on chromosome 15q26; FPLD5 (615238) is caused by mutation in the CIDEC gene (612120) on chromosome 3p25; FPLD6 (615980) is caused by mutation in the LIPE gene (151750) on chromosome 19q13; FPLD7 (606721) is caused by mutation in the CAV1 gene (601047) on chromosome 7q31; FPLD8 (620679), caused by mutation in the ADRA2A gene (104210) on chromosome 10q25; and FPLD9 (620683), caused by mutation in the PLAAT3 gene (613867) on chromosome 11q12.
PPARG-related familial partial lipodystrophy
MedGen UID:
328393
Concept ID:
C1720861
Disease or Syndrome
A rare familial partial lipodystrophy with characteristics of adult onset of distal lipoatrophy with gluteofemoral fat loss, as well as increased fat accumulation in the face and trunk and visceral adiposity. Additional manifestations include diabetes mellitus, atherogenic dyslipidemia, eyelid xanthelasma, arterial hypertension, cardiovascular disease, hepatic steatosis, acanthosis nigricans on axilla and neck, hirsutism, and muscular hypertrophy of the lower limbs. Caused by heterozygous mutation in the PPARG gene on chromosome 3p25.
Congenital generalized lipodystrophy type 1
MedGen UID:
318592
Concept ID:
C1720862
Disease or Syndrome
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Congenital generalized lipodystrophy type 2
MedGen UID:
318593
Concept ID:
C1720863
Congenital Abnormality
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Familial hemophagocytic lymphohistiocytosis 3
MedGen UID:
332383
Concept ID:
C1837174
Disease or Syndrome
Secretion of the contents of cytolytic granules at the immunologic synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin (170280)-containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. Familial hemophagocytic lymphohistiocytosis is a genetically heterogeneous condition characterized by defective cytotoxicity. For a more detailed description of FHL, see 267700.
Hyperlipoproteinemia, type II, and deafness
MedGen UID:
326732
Concept ID:
C1840425
Disease or Syndrome
X-linked lymphoproliferative disease due to XIAP deficiency
MedGen UID:
336848
Concept ID:
C1845076
Disease or Syndrome
X-linked lymphoproliferative disease (XLP) has two recognizable subtypes, XLP1 and XLP2. XLP1 is characterized predominantly by one of three commonly recognized phenotypes: Inappropriate immune response to Epstein-Barr virus (EBV) infection leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis. Dysgammaglobulinemia. Lymphoproliferative disease (malignant lymphoma). XLP2 is most often characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease. HLH resulting from EBV infection is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The malignant lymphomas are typically B-cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.
Familial isolated deficiency of vitamin E
MedGen UID:
341248
Concept ID:
C1848533
Disease or Syndrome
Ataxia with vitamin E deficiency (AVED) generally manifests in late childhood or early teens between ages five and 15 years. The first symptoms include progressive ataxia, clumsiness of the hands, loss of proprioception, and areflexia. Other features often observed are dysdiadochokinesia, dysarthria, positive Romberg sign, head titubation, decreased visual acuity, and positive Babinski sign. The phenotype and disease severity vary widely among families with different pathogenic variants; age of onset and disease course are more uniform within a given family, but symptoms and disease severity can vary even among sibs.
Neutral lipid storage myopathy
MedGen UID:
339913
Concept ID:
C1853136
Disease or Syndrome
Neutral lipid storage disease with myopathy (NLSDM) is an autosomal recessive muscle disorder characterized by adult onset of slowly progressive proximal muscle weakness affecting the upper and lower limbs and associated with increased serum creatine kinase; distal muscle weakness may also occur. About half of patients develop cardiomyopathy later in the disease course. Other variable features include diabetes mellitus, hepatic steatosis, hypertriglyceridemia, and possibly sensorineural hearing loss. Leukocytes and muscle cells show cytoplasmic accumulation of triglycerides (summary by Reilich et al., 2011). Neutral lipid storage disease with myopathy belongs to a group of disorders termed neutral lipid storage disorders (NLSDs). These disorders are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Chanarin-Dorfman syndrome (CDS; 275630) is defined as NLSD with ichthyosis (NLSDI). Patients with NLSDM present with myopathy but without ichthyosis (summary by Fischer et al., 2007).
Neonatal intrahepatic cholestasis due to citrin deficiency
MedGen UID:
340091
Concept ID:
C1853942
Disease or Syndrome
Citrin deficiency can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2). Often citrin deficiency is characterized by strong preference for protein-rich and/or lipid-rich foods and aversion to carbohydrate-rich foods. NICCD. Children younger than age one year have a history of low birth weight with growth restriction and transient intrahepatic cholestasis, hepatomegaly, diffuse fatty liver, and parenchymal cellular infiltration associated with hepatic fibrosis, variable liver dysfunction, hypoproteinemia, decreased coagulation factors, hemolytic anemia, and/or hypoglycemia. NICCD is generally not severe and symptoms often resolve by age one year with appropriate treatment, although liver transplantation has been required in rare instances. FTTDCD. Beyond age one year, many children with citrin deficiency develop a protein-rich and/or lipid-rich food preference and aversion to carbohydrate-rich foods. Clinical abnormalities may include growth restriction, hypoglycemia, pancreatitis, severe fatigue, anorexia, and impaired quality of life. Laboratory changes are dyslipidemia, increased lactate-to-pyruvate ratio, higher levels of urinary oxidative stress markers, and considerable deviation in tricarboxylic acid (TCA) cycle metabolites. One or more decades later, some individuals with NICCD or FTTDCD develop CTLN2. CTLN2. Presentation is sudden and usually between ages 20 and 50 years. Manifestations are recurrent hyperammonemia with neuropsychiatric symptoms including nocturnal delirium, aggression, irritability, hyperactivity, delusions, disorientation, restlessness, drowsiness, loss of memory, flapping tremor, convulsive seizures, and coma. Symptoms are often provoked by alcohol and sugar intake, medication, and/or surgery. Affected individuals may or may not have a prior history of NICCD or FTTDCD.
Lipase deficiency, combined
MedGen UID:
340886
Concept ID:
C1855498
Disease or Syndrome
A rare disorder caused by mutation in the LMF1 gene resulting in combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders.
Hypercholesterolemia, familial, 4
MedGen UID:
400313
Concept ID:
C1863512
Disease or Syndrome
Familial hypercholesterolemia (FH) is characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) that leads to atherosclerotic plaque deposition in the coronary arteries and proximal aorta at an early age and increases the risk of premature cardiovascular events such as angina and myocardial infarction; stroke occurs more rarely. Xanthomas (cholesterol deposits in tendons) may be visible in the Achilles tendons or tendons of the hands and worsen with age as a result of extremely high cholesterol levels. Xanthelasmas (yellowish, waxy deposits) can occur around the eyelids. Individuals with FH may develop corneal arcus (white, gray, or blue opaque ring in the corneal margin as a result of cholesterol deposition) at a younger age than those without FH. Individuals with a more severe phenotype, often as a result of biallelic variants, can present with very significant elevations in LDL-C (>500 mg/dL), early-onset coronary artery disease (CAD; presenting as early as childhood in some), and calcific aortic valve disease.
Familial hemophagocytic lymphohistiocytosis 2
MedGen UID:
400366
Concept ID:
C1863727
Disease or Syndrome
Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia. There is increased production of cytokines, such as gamma-interferon (IFNG; 147570) and TNF-alpha (191160), by hyperactivation and proliferation of T cells and macrophages. Activity of cytotoxic T cells and NK cells is reduced, consistent with a defect in cellular cytotoxicity. Bone marrow, lymph nodes, spleen, and liver show features of hemophagocytosis. Chemotherapy and/or immunosuppressant therapy may result in symptomatic remission, but the disorder is fatal without bone marrow transplantation (summary by Dufourcq-Lagelouse et al., 1999, Stepp et al., 1999, and Molleran Lee et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of FHL, see 267700.
Familial hemophagocytic lymphohistiocytosis 4
MedGen UID:
350245
Concept ID:
C1863728
Disease or Syndrome
Hemophagocytic lymphohistiocytosis is a hyperinflammatory disorder clinically diagnosed based on the fulfillment of 5 of 8 criteria, including fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low or absent natural killer (NK) cell activity, hyperferritinemia, and high soluble IL2 receptor levels (IL2R; 147730). The disorder typically presents in infancy or early childhood. Persistent remission is rarely achieved with chemo- or immunotherapy; hematopoietic stem cell transplantation is the only cure (summary by Muller et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL), see 267700.
Citrullinemia type II
MedGen UID:
350276
Concept ID:
C1863844
Disease or Syndrome
Citrin deficiency can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2). Often citrin deficiency is characterized by strong preference for protein-rich and/or lipid-rich foods and aversion to carbohydrate-rich foods. NICCD. Children younger than age one year have a history of low birth weight with growth restriction and transient intrahepatic cholestasis, hepatomegaly, diffuse fatty liver, and parenchymal cellular infiltration associated with hepatic fibrosis, variable liver dysfunction, hypoproteinemia, decreased coagulation factors, hemolytic anemia, and/or hypoglycemia. NICCD is generally not severe and symptoms often resolve by age one year with appropriate treatment, although liver transplantation has been required in rare instances. FTTDCD. Beyond age one year, many children with citrin deficiency develop a protein-rich and/or lipid-rich food preference and aversion to carbohydrate-rich foods. Clinical abnormalities may include growth restriction, hypoglycemia, pancreatitis, severe fatigue, anorexia, and impaired quality of life. Laboratory changes are dyslipidemia, increased lactate-to-pyruvate ratio, higher levels of urinary oxidative stress markers, and considerable deviation in tricarboxylic acid (TCA) cycle metabolites. One or more decades later, some individuals with NICCD or FTTDCD develop CTLN2. CTLN2. Presentation is sudden and usually between ages 20 and 50 years. Manifestations are recurrent hyperammonemia with neuropsychiatric symptoms including nocturnal delirium, aggression, irritability, hyperactivity, delusions, disorientation, restlessness, drowsiness, loss of memory, flapping tremor, convulsive seizures, and coma. Symptoms are often provoked by alcohol and sugar intake, medication, and/or surgery. Affected individuals may or may not have a prior history of NICCD or FTTDCD.
Alagille syndrome due to a JAG1 point mutation
MedGen UID:
365434
Concept ID:
C1956125
Disease or Syndrome
Alagille syndrome (ALGS) is a multisystem disorder with a wide spectrum of clinical variability; this variability is seen even among individuals from the same family. The major clinical manifestations of ALGS are bile duct paucity on liver biopsy, cholestasis, congenital cardiac defects (primarily involving the pulmonary arteries), butterfly vertebrae, ophthalmologic abnormalities (most commonly posterior embryotoxon), and characteristic facial features. Renal abnormalities, growth failure, developmental delays, splenomegaly, and vascular abnormalities may also occur.
Coronary artery disease, autosomal dominant 2
MedGen UID:
370259
Concept ID:
C1970440
Disease or Syndrome
Any coronary artery disease in which the cause of the disease is a mutation in the LRP6 gene.
Congenital generalized lipodystrophy type 3
MedGen UID:
436541
Concept ID:
C2675861
Disease or Syndrome
Congenital generalized lipodystrophy, also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis, and early onset of diabetes (Garg, 2004). For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594).
Emery-Dreifuss muscular dystrophy 3, autosomal recessive
MedGen UID:
413212
Concept ID:
C2750035
Disease or Syndrome
Emery-Dreifuss muscular dystrophy is characterized classically by the triad of weakness of the shoulder and pelvic girdle muscles, contractures of the elbows, neck, and Achilles tendon, and cardiac involvement, most commonly arrhythmias (summary by Jimenez-Escrig et al., 2012). For a discussion of genetic heterogeneity of EDMD, see 310300.
Congenital generalized lipodystrophy type 4
MedGen UID:
412871
Concept ID:
C2750069
Disease or Syndrome
Congenital generalized lipodystrophy type 4 (CGL4) combines the phenotype of classic Berardinelli-Seip lipodystrophy (608594) with muscular dystrophy and cardiac conduction anomalies (Hayashi et al., 2009). For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594).
Familial hemophagocytic lymphohistiocytosis 5
MedGen UID:
416514
Concept ID:
C2751293
Disease or Syndrome
Familial hemophagocytic lymphohistiocytosis-5 with or without microvillus inclusion disease (FHL5) is an autosomal recessive hyperinflammatory disorder characterized clinically by fever, hepatosplenomegaly, pancytopenia, coagulation abnormalities, and other laboratory findings. Some patients have neurologic symptoms due to inflammatory CNS disease. There is uncontrolled and ineffective proliferation and activation of T lymphocytes, NK cells, and macrophages that infiltrate multiple organs, including liver, spleen, lymph nodes, and the CNS. The phenotype is variable: some patients may present in early infancy with severe diarrhea, prior to the onset of typical FHL features, whereas others present later in childhood and have a more protracted course without diarrhea. The early-onset diarrhea is due to enteropathy reminiscent of microvillus inclusion disease (see MVID, 251850). The enteropathy, which often necessitates parenteral feeding, may be the most life-threatening issue even after hematopoietic stem cell transplantation (HSCT). More variable features include sensorineural hearing loss and hypogammaglobulinemia. Treatment with immunosuppressive drugs and chemotherapy can ameliorate signs and symptoms of FHL in some patients, but the only curative therapy for FHL is HSCT. HSCT is not curative for enteropathy associated with the disorder, despite hematologic and immunologic reconstitution (summary by Meeths et al., 2010; Pagel et al., 2012; Stepensky et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL, HLH), see 267700.
Glycogen storage disease IXc
MedGen UID:
442778
Concept ID:
C2751643
Disease or Syndrome
Phosphorylase kinase (PhK) deficiency causing glycogen storage disease type IX (GSD IX) results from deficiency of the enzyme phosphorylase b kinase, which has a major regulatory role in the breakdown of glycogen. The two types of PhK deficiency are liver PhK deficiency (characterized by early childhood onset of hepatomegaly and growth restriction, and often, but not always, fasting ketosis and hypoglycemia) and muscle PhK deficiency, which is considerably rarer (characterized by any of the following: exercise intolerance, myalgia, muscle cramps, myoglobinuria, and progressive muscle weakness). While symptoms and biochemical abnormalities of liver PhK deficiency were thought to improve with age, it is becoming evident that affected individuals need to be monitored for long-term complications such as liver fibrosis and cirrhosis.
Palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome
MedGen UID:
461281
Concept ID:
C3149931
Disease or Syndrome
Palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome is characterised by sex reversal in males with a 46, XX (SRY-negative) karyotype, palmoplantar hyperkeratosis and a predisposition to squamous cell carcinoma. To date, five cases (four of whom were brothers) have been described. The aetiology is unknown.
Hyperlipidemia due to hepatic triglyceride lipase deficiency
MedGen UID:
462816
Concept ID:
C3151466
Disease or Syndrome
Hepatic lipase deficiency is characterized by premature atherosclerosis, elevated total cholesterol, triglycerides (TG), and very low density lipoprotein (VLDL), as well as TG-rich low density lipoprotein (LDL) and HDL subfractions (summary by Hegele et al., 1991).
Transient infantile hypertriglyceridemia and hepatosteatosis
MedGen UID:
482583
Concept ID:
C3280953
Disease or Syndrome
Transient infantile hypertriglyceridemia (HTGTI) is an autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis. The long-term outcome of affected individuals is unclear (summary by Basel-Vanagaite et al., 2012).
Glycogen storage disease IXa1
MedGen UID:
854172
Concept ID:
C3694531
Disease or Syndrome
Phosphorylase kinase (PhK) deficiency causing glycogen storage disease type IX (GSD IX) results from deficiency of the enzyme phosphorylase b kinase, which has a major regulatory role in the breakdown of glycogen. The two types of PhK deficiency are liver PhK deficiency (characterized by early childhood onset of hepatomegaly and growth restriction, and often, but not always, fasting ketosis and hypoglycemia) and muscle PhK deficiency, which is considerably rarer (characterized by any of the following: exercise intolerance, myalgia, muscle cramps, myoglobinuria, and progressive muscle weakness). While symptoms and biochemical abnormalities of liver PhK deficiency were thought to improve with age, it is becoming evident that affected individuals need to be monitored for long-term complications such as liver fibrosis and cirrhosis.
Mandibular hypoplasia-deafness-progeroid syndrome
MedGen UID:
811623
Concept ID:
C3715192
Disease or Syndrome
Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance, and metabolic abnormalities including insulin resistance and diabetes mellitus. Sensorineural deafness occurs late in the first or second decades of life (summary by Weedon et al., 2013).
Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome
MedGen UID:
813897
Concept ID:
C3807567
Disease or Syndrome
Lipodystrophies are rare disorders characterized by loss of body fat from various regions and predisposition to metabolic complications of insulin resistance and lipid abnormalities. FPLD7 is an autosomal dominant disorder with a highly variable phenotype. Additional features, including early-onset cataracts and later onset of spasticity of the lower limbs, have been noted in some patients (summary by Garg et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.
CIDEC-related familial partial lipodystrophy
MedGen UID:
815270
Concept ID:
C3808940
Disease or Syndrome
A rare genetic lipodystrophy with characteristics of abnormal subcutaneous fat distribution, resulting in preservation of visceral, neck and axillary fat and absence of lower limb and gluteofemoral subcutaneous fat. Additional clinical features are acanthosis nigricans, insulin-resistant type II diabetes mellitus, dyslipidaemia, and hypertension, leading to pancreatitis, hepatomegaly and hepatic steatosis.
Obesity due to CEP19 deficiency
MedGen UID:
816654
Concept ID:
C3810324
Disease or Syndrome
A rare, genetic form of obesity characterized by morbid obesity, hypertension, type 2 diabetes mellitus and dyslipidemia leading to early coronary disease, myocardial infarction and congestive heart failure. Intellectual disability and decreased sperm counts or azoospermia have also been reported.
Abdominal obesity-metabolic syndrome 3
MedGen UID:
862798
Concept ID:
C4014361
Disease or Syndrome
Any metabolic syndrome in which the cause of the disease is a mutation in the DYRK1B gene.
Severe neurodegenerative syndrome with lipodystrophy
MedGen UID:
863137
Concept ID:
C4014700
Disease or Syndrome
The spectrum of BSCL2-related neurologic disorders includes Silver syndrome and variants of Charcot-Marie-Tooth neuropathy type 2, distal hereditary motor neuropathy (dHMN) type V, and spastic paraplegia 17. Features of these disorders include onset of symptoms ranging from the first to the seventh decade, slow disease progression, upper motor neuron involvement (gait disturbance with pyramidal signs ranging from mild to severe spasticity with hyperreflexia in the lower limbs and variable extensor plantar responses), lower motor neuron involvement (amyotrophy of the peroneal muscles and small muscles of the hand), and pes cavus and other foot deformities. Disease severity is variable among and within families.
Hyperlipoproteinemia, type 1D
MedGen UID:
863204
Concept ID:
C4014767
Disease or Syndrome
Hyperlipoproteinemia type ID is a rare autosomal recessive disorder characterized by impaired clearance of triglyceride (TG)-rich lipoproteins in plasma, leading to severe hypertriglyceridemia (chylomicronemia). Clinical features include eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, episodes of abdominal pain, and pancreatitis. Onset usually occurs in adulthood (summary by Brahm and Hegele, 2013). For a discussion of genetic heterogeneity of familial chylomicronemia, see 238600.
Motor developmental delay due to 14q32.2 paternally expressed gene defect
MedGen UID:
863995
Concept ID:
C4015558
Disease or Syndrome
Temple syndrome is a short stature disorder of imprinting. The cardinal features are low birth weight, hypotonia and motor delay, feeding problems early in life, early puberty, and significantly reduced final height. Facial features include a broad forehead and short nose with a wide nasal tip, and the majority of patients have small hands and feet. However, many of the clinical features are nonspecific, making diagnosis difficult. In addition, isodisomy may uncover recessive disorders, which may influence the phenotype in maternal uniparental disomy of chromosome 14 (UPD14mat) cases (summary by Ioannides et al., 2014).
Seckel syndrome 10
MedGen UID:
934614
Concept ID:
C4310647
Disease or Syndrome
Any Seckel syndrome in which the cause of the disease is a mutation in the NSMCE2 gene.
Nephrotic syndrome 14
MedGen UID:
1617660
Concept ID:
C4540559
Disease or Syndrome
Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is characterized by varying combinations of steroid-resistant nephrotic syndrome (ranging from nonimmune fetal hydrops to adolescent onset), primary adrenal insufficiency (with or without mineralocorticoid deficiency), testicular insufficiency, hypothyroidism, ichthyosis, lymphopenia/immunodeficiency, and neurologic abnormalities that can include developmental delay, regression / progressive neurologic involvement, cranial nerve deficits, and peripheral motor and sensory neuropathy.
Familial hemophagocytic lymphohistiocytosis type 1
MedGen UID:
1642840
Concept ID:
C4551514
Disease or Syndrome
Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare primary immunodeficiency characterized by a macrophage activation syndrome with an onset usually occurring within a few months or less common several years after birth.
Familial hypobetalipoproteinemia 1
MedGen UID:
1639219
Concept ID:
C4551990
Disease or Syndrome
Individuals with biallelic APOB-related familial hypobetalipoproteinemia (APOB-FHBL) may present from infancy through to adulthood with a range of clinical symptoms including deficiency of fat-soluble vitamins and gastrointestinal and neurologic dysfunction. Affected individuals typically have plasma total cholesterol, LDL cholesterol, and apo B levels below the fifth centile for age and sex. Acanthocytosis, elevated liver enzymes, and hyperbilirubinemia may also be found. The most common clinical findings are hepatomegaly, steatorrhea, and failure to thrive / growth deficiency. In the absence of treatment, affected individuals can develop atypical pigmentation of the retina; progressive loss of deep tendon reflexes, vibratory sense, and proprioception; muscle pain or weakness; dysarthria; ataxia; tremors; and steatohepatitis, fibrosis, and rarely, cirrhosis of the liver. Individuals with a heterozygous, typically truncating pathogenic variant in APOB are usually asymptomatic with mild liver dysfunction and hepatic steatosis. However, about 5%-10% of individuals with heterozygous APOB-FHBL develop relatively more severe nonalcoholic steatohepatitis requiring medical attention and occasionally progressing to cirrhosis, albeit very rarely.
Protoporphyria, erythropoietic, 1
MedGen UID:
1643471
Concept ID:
C4692546
Disease or Syndrome
Erythropoietic protoporphyria (EPP) is characterized by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within 30 minutes after exposure to sun or ultraviolet light and may be accompanied by swelling and redness. Symptoms (which may seem out of proportion to the visible skin lesions) may persist for hours or days after the initial phototoxic reaction. Photosensitivity remains for life. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. Approximately 20%-30% of individuals with EPP have some degree of liver dysfunction, which is typically mild with slight elevations of the liver enzymes. Up to 5% may develop more advanced liver disease which may be accompanied by motor neuropathy similar to that seen in the acute porphyrias.
BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 19
MedGen UID:
1638030
Concept ID:
C4693522
Finding
Patients with biallelic mutations in the ADCY3 gene show hyperphagia within the first 2 years of life and develop severe obesity. Other features include hyposmia or anosmia, and some patients exhibit mild to moderate intellectual disability (Saeed et al., 2018).
Proteasome-associated autoinflammatory syndrome 1
MedGen UID:
1648310
Concept ID:
C4746851
Disease or Syndrome
Proteasome-associated autoinflammatory syndrome-1 (PRAAS1) is an autosomal recessive disorder characterized by early childhood onset of annular erythematous plaques on the face and extremities with subsequent development of partial lipodystrophy and laboratory evidence of immune dysregulation. More variable features include recurrent fever, severe joint contractures, muscle weakness and atrophy, hepatosplenomegaly, basal ganglia calcifications, and microcytic anemia (summary by Agarwal et al., 2010; Kitamura et al., 2011; Arima et al., 2011). This disorder encompasses Nakajo-Nishimura syndrome (NKJO); joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). Among Japanese patients, this disorder is best described as Nakajo-Nishimura syndrome, since both Nakajo (1939) and Nishimura et al. (1950) contributed to the original phenotypic descriptions. Genetic Heterogeneity of Proteasome-Associated Autoinflammatory Syndrome See also PRAAS2 (618048), caused by mutation in the POMP gene (613386) on chromosome 13q12; PRAAS3 (617591), caused by mutation in the PSMB4 gene (602177) on chromosome 1q21; PRAAS4 (619183), caused by mutation in the PSMG2 gene (609702) on chromosome 18p11; PRAAS5 (619175), caused by mutation in the PSMB10 gene (176847) on chromosome 16q22; and PRAAS6 (620796), caused by mutation in the PSMB9 gene (177045) on chromosome 6p21.
Proteasome-associated autoinflammatory syndrome 3
MedGen UID:
1648456
Concept ID:
C4747850
Disease or Syndrome
Proteasome-associated autoinflammatory syndrome-3 is an autosomal recessive syndrome with onset in early infancy. Affected individuals present with nodular dermatitis, recurrent fever, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and dysregulation of the immune response, particularly associated with abnormal type I interferon-induced gene expression patterns. Additional features are highly variable, but may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications (summary by Brehm et al., 2015). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).
Glycosylphosphatidylinositol biosynthesis defect 17
MedGen UID:
1648437
Concept ID:
C4747891
Disease or Syndrome
Glycosylphosphatidylinositol biosynthesis defect-17 (GPIBD17) is an autosomal recessive disorder characterized by variable neurologic deficits that become apparent in infancy or early childhood. Patients may present with early-onset febrile or afebrile seizures that tend to be mild or controllable. Other features may include learning disabilities, autism, behavioral abnormalities, hypotonia, and motor deficits. The phenotype is relatively mild compared to that of other GPIBDs (summary by Nguyen et al., 2018). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Diarrhea 10, protein-losing enteropathy type
MedGen UID:
1648311
Concept ID:
C4748579
Disease or Syndrome
Diarrhea-10 (DIAR10) is a protein-losing enteropathy characterized by intractable secretory diarrhea and massive protein loss due to leaky fenestrated capillaries. Features include early-onset anasarca, severe hypoalbuminemia, hypogammaglobulinemia, and hypertriglyceridemia, as well as electrolyte abnormalities. Some patients exhibit facial dysmorphism and cardiac and renal anomalies. Intrafamilial variability has been observed, and the disease can be severe, with death occurring in infancy in some patients (Broekaert et al., 2018; Kurolap et al., 2018). For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
PLIN1-related familial partial lipodystrophy
MedGen UID:
1675945
Concept ID:
C5191005
Disease or Syndrome
Familial partial lipodystrophy type 4 is an autosomal dominant metabolic disorder characterized by childhood or young adult onset of loss of subcutaneous adipose tissue primarily affecting the lower limbs, insulin-resistant diabetes mellitus, hypertriglyceridemia, and hypertension (summary by Gandotra et al., 2011). Other features may include hepatic steatosis, acanthosis nigricans, polycystic ovary syndrome, and renal disease (summary by Chen et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.
Abdominal obesity-metabolic syndrome 4
MedGen UID:
1704861
Concept ID:
C5231430
Disease or Syndrome
Abdominal obesity-metabolic syndrome-4 (AOMS4) is characterized by obesity, hypertension, and early-onset coronary artery disease. Most affected individuals meet the criteria for metabolic syndrome, including elevated triglyceride and low high-density lipoprotein levels, and type 2 diabetes (Esteghamat et al., 2019). For a discussion of the genetic heterogeneity of abdominal obesity-metabolic syndrome, see AOMS1 (605552).
Hypoalphalipoproteinemia, primary, 1
MedGen UID:
1684828
Concept ID:
C5231558
Disease or Syndrome
Any ypoalphalipoproteinemia in which the cause of the disease is a mutation in the ABCA1 gene.
Rajab interstitial lung disease with brain calcifications 2
MedGen UID:
1770895
Concept ID:
C5436603
Disease or Syndrome
Rajab interstitial lung disease with brain calcifications-2 (RILDBC2) is an autosomal recessive disorder characterized by growth delay, interstitial lung disease, liver disease, and abnormal brain MRI findings, including brain calcifications and periventricular cysts (Krenke et al., 2019). For a discussion of genetic heterogeneity of RILDBC, see RILDBC1 (613658).
Mandibuloacral dysplasia progeroid syndrome
MedGen UID:
1741713
Concept ID:
C5436867
Disease or Syndrome
Mandibuloacral dysplasia progeroid syndrome (MDPS) is an autosomal recessive severe laminopathy-like disorder characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis, and hypertension (Elouej et al., 2020).
Hypertriglyceridemia 1
MedGen UID:
1787149
Concept ID:
C5444012
Disease or Syndrome
Proteasome-associated autoinflammatory syndrome 5
MedGen UID:
1779962
Concept ID:
C5543027
Disease or Syndrome
Immunodeficiency 80 with or without congenital cardiomyopathy
MedGen UID:
1786417
Concept ID:
C5543344
Disease or Syndrome
Immunodeficiency-80 with or without congenital cardiomyopathy (IMD80) is an autosomal recessive immunologic disorder with variable manifestations. One patient with infantile-onset of chronic cytomegalovirus (CMV) infection associated with severely decreased NK cells has been reported. Another family with 3 affected fetuses showing restrictive cardiomyopathy and hypoplasia of the spleen and thymus has also been reported (summary by Baxley et al., 2021).
Hypertriglyceridemia 2
MedGen UID:
1783778
Concept ID:
C5543398
Disease or Syndrome
Hypertriglyceridemia-2 (HYTG2) is characterized by moderately to severely elevated plasma triglyceride levels, increased total cholesterol levels, and low levels of high density lipoprotein (HDL) cholesterol. Reduced penetrance has been observed (Lee et al., 2011; Cefalu et al., 2015).
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2
MedGen UID:
1778117
Concept ID:
C5543623
Disease or Syndrome
Infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2) is an autosomal recessive multisystemic disorder characterized by cholestatic hepatitis, poor feeding associated with poor overall growth, and hypoglycemia apparent from infancy. Most, but not all, patients have variable global developmental delay. Additional common features include sensorineural deafness, retinal abnormalities with visual defects, and hypotonia. Some patients have endocrine abnormalities, including hyperinsulinemic hypoglycemia, pancreatic dysfunction, hypothyroidism, and primary amenorrhea. Additional features may include hypertriglyceridemia, anemia, proteinuria, increased lactate, and recurrent infections. Brain imaging often shows dysmyelination, thin corpus callosum, cerebral atrophy, and white matter abnormalities. Although the clinical manifestations and severity of the disorder are highly variable, death in early childhood may occur (summary by Williams et al., 2019 and Zeiad et al., 2021). For a discussion of genetic heterogeneity of IMNEPD, see IMNEPD1 (616263).
Immunodeficiency 87 and autoimmunity
MedGen UID:
1794280
Concept ID:
C5562070
Disease or Syndrome
Immunodeficiency-87 and autoimmunity (IMD87) is an autosomal recessive immunologic disorder with wide phenotypic variation and severity. Affected individuals usually present in infancy or early childhood with increased susceptibility to infections, often Epstein-Barr virus (EBV), as well as with lymphadenopathy or autoimmune manifestations, predominantly hemolytic anemia. Laboratory studies may show low or normal lymphocyte numbers, often with skewed T-cell subset ratios. The disorder results primarily from defects in T-cell function, which causes both immunodeficiency and overall immune dysregulation (summary by Serwas et al., 2019 and Fournier et al., 2021).
Immunodeficiency 97 with autoinflammation
MedGen UID:
1802936
Concept ID:
C5676946
Disease or Syndrome
Immunodeficiency-97 with autoinflammation (IMD97) is an autosomal recessive complex immunologic disorder with variable features. Affected individuals present in the first decade of life with inflammatory interstitial lung disease or colitis due to abnormal tissue infiltration by activated T cells. Patients develop autoimmune cytopenias and may have lymphadenopathy; 1 reported patient had features of hemophagocytic lymphohistiocytosis (HLH; see FHL1, 267700). Some patients may have recurrent infections associated with mild lymphopenia, hypogammaglobulinemia, and NK cell dysfunction. Immunologic workup indicates signs of significant immune dysregulation with elevation of inflammatory serum markers, variable immune cell defects involving neutrophils, NK cells, and myeloid cells, and disrupted levels of T regulatory cells (Tregs). Two unrelated patients have been reported (summary by Takeda et al., 2019 and Thian et al., 2020).
Immunodeficiency 109 with lymphoproliferation
MedGen UID:
1840982
Concept ID:
C5830346
Disease or Syndrome
Immunodeficiency-109 with EBV-induced lymphoproliferation (IMD109) is an autosomal recessive primary immune disorder characterized by onset of recurrent sinopulmonary infections in childhood. Affected individuals are susceptible to infection with EBV and develop EBV viremia and EBV-associated lymphoproliferative disease or B-cell lymphoma. Immunologic work-up shows normal levels of T, B, and NK cells, with defective CD8+ T cell function after stimulation. Some patients may have hypogammaglobulinemia and poor antibody response to stimulation (Alosaimi et al., 2019).

Professional guidelines

PubMed

Simha V
BMJ 2020 Oct 12;371:m3109. doi: 10.1136/bmj.m3109. PMID: 33046451
Parhofer KG, Laufs U
Dtsch Arztebl Int 2019 Dec 6;116(49):825-832. doi: 10.3238/arztebl.2019.0825. PMID: 31888796Free PMC Article
Mayfield J
Am Fam Physician 1998 Oct 15;58(6):1355-62, 1369-70. PMID: 9803200

Recent clinical studies

Etiology

Chait A
Endocrinol Metab Clin North Am 2022 Sep;51(3):539-555. Epub 2022 Jul 4 doi: 10.1016/j.ecl.2022.02.010. PMID: 35963627
Simha V
BMJ 2020 Oct 12;371:m3109. doi: 10.1136/bmj.m3109. PMID: 33046451
Packard CJ, Boren J, Taskinen MR
Front Endocrinol (Lausanne) 2020;11:252. Epub 2020 May 14 doi: 10.3389/fendo.2020.00252. PMID: 32477261Free PMC Article
Parhofer KG, Laufs U
Dtsch Arztebl Int 2019 Dec 6;116(49):825-832. doi: 10.3238/arztebl.2019.0825. PMID: 31888796Free PMC Article
Garg R, Rustagi T
Biomed Res Int 2018;2018:4721357. Epub 2018 Jul 26 doi: 10.1155/2018/4721357. PMID: 30148167Free PMC Article

Diagnosis

Mądro A
Int J Environ Res Public Health 2022 Dec 3;19(23) doi: 10.3390/ijerph192316179. PMID: 36498253Free PMC Article
Wierzbicki AS, Kim EJ, Esan O, Ramachandran R
J Clin Pathol 2022 Dec;75(12):798-806. Epub 2022 Jun 16 doi: 10.1136/jclinpath-2021-207719. PMID: 35710321
Mauri M, Calmarza P, Ibarretxe D
Clin Investig Arterioscler 2021 Jan-Feb;33(1):41-52. Epub 2020 Dec 9 doi: 10.1016/j.arteri.2020.10.002. PMID: 33309071
Parhofer KG, Laufs U
Dtsch Arztebl Int 2019 Dec 6;116(49):825-832. doi: 10.3238/arztebl.2019.0825. PMID: 31888796Free PMC Article
Nordestgaard BG, Varbo A
Lancet 2014 Aug 16;384(9943):626-635. doi: 10.1016/S0140-6736(14)61177-6. PMID: 25131982

Therapy

Shi Y, Guo L, Chen Y, Xie Q, Yan Z, Liu Y, Kang J, Li S
Folia Neuropathol 2021;59(4):378-385. doi: 10.5114/fn.2021.112007. PMID: 35114778
Nicholls SJ, Lincoff AM, Garcia M, Bash D, Ballantyne CM, Barter PJ, Davidson MH, Kastelein JJP, Koenig W, McGuire DK, Mozaffarian D, Ridker PM, Ray KK, Katona BG, Himmelmann A, Loss LE, Rensfeldt M, Lundström T, Agrawal R, Menon V, Wolski K, Nissen SE
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Watanabe Y, Tatsuno I
J Atheroscler Thromb 2020 Mar 1;27(3):183-198. Epub 2019 Oct 3 doi: 10.5551/jat.50658. PMID: 31582621Free PMC Article
Parhofer KG, Laufs U
Dtsch Arztebl Int 2019 Dec 6;116(49):825-832. doi: 10.3238/arztebl.2019.0825. PMID: 31888796Free PMC Article
Rawla P, Sunkara T, Thandra KC, Gaduputi V
Clin J Gastroenterol 2018 Dec;11(6):441-448. Epub 2018 Jun 19 doi: 10.1007/s12328-018-0881-1. PMID: 29923163

Prognosis

Lin XY, Zeng Y, Zhang ZC, Lin ZH, Chen LC, Ye ZS
World J Gastroenterol 2022 Aug 7;28(29):3946-3959. doi: 10.3748/wjg.v28.i29.3946. PMID: 36157550Free PMC Article
Chaitman BR, Alexander KP, Cyr DD, Berger JS, Reynolds HR, Bangalore S, Boden WE, Lopes RD, Demkow M, Piero Perna G, Riezebos RK, McFalls EO, Banerjee S, Bagai A, Gosselin G, O'Brien SM, Rockhold FW, Waters DD, Thygesen KA, Stone GW, White HD, Maron DJ, Hochman JS; ISCHEMIA Research Group
Circulation 2021 Feb 23;143(8):790-804. Epub 2020 Dec 3 doi: 10.1161/CIRCULATIONAHA.120.047987. PMID: 33267610Free PMC Article
Sampson M, Ling C, Sun Q, Harb R, Ashmaig M, Warnick R, Sethi A, Fleming JK, Otvos JD, Meeusen JW, Delaney SR, Jaffe AS, Shamburek R, Amar M, Remaley AT
JAMA Cardiol 2020 May 1;5(5):540-548. doi: 10.1001/jamacardio.2020.0013. PMID: 32101259Free PMC Article
Wilky BA, Trucco MM, Subhawong TK, Florou V, Park W, Kwon D, Wieder ED, Kolonias D, Rosenberg AE, Kerr DA, Sfakianaki E, Foley M, Merchan JR, Komanduri KV, Trent JC
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Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators
N Engl J Med 2019 Jan 3;380(1):11-22. Epub 2018 Nov 10 doi: 10.1056/NEJMoa1812792. PMID: 30415628

Clinical prediction guides

Kiss L, Fűr G, Pisipati S, Rajalingamgari P, Ewald N, Singh V, Rakonczay Z Jr
Acta Physiol (Oxf) 2023 Mar;237(3):e13916. Epub 2023 Jan 13 doi: 10.1111/apha.13916. PMID: 36599412
Mądro A
Int J Environ Res Public Health 2022 Dec 3;19(23) doi: 10.3390/ijerph192316179. PMID: 36498253Free PMC Article
Raposeiras-Roubin S, Rosselló X, Oliva B, Fernández-Friera L, Mendiguren JM, Andrés V, Bueno H, Sanz J, Martínez de Vega V, Abu-Assi E, Iñiguez A, Fernández-Ortiz A, Ibáñez B, Fuster V
J Am Coll Cardiol 2021 Jun 22;77(24):3031-3041. doi: 10.1016/j.jacc.2021.04.059. PMID: 34140107Free PMC Article
Liberis A, Petousis S, Tsikouras P
Curr Pharm Des 2021;27(36):3804-3807. doi: 10.2174/1381612827666210421103245. PMID: 33882801
Sandesara PB, Virani SS, Fazio S, Shapiro MD
Endocr Rev 2019 Apr 1;40(2):537-557. doi: 10.1210/er.2018-00184. PMID: 30312399Free PMC Article

Recent systematic reviews

Zhong L, Liu J, Liu S, Tan G
Front Endocrinol (Lausanne) 2023;14:1116582. Epub 2023 Apr 11 doi: 10.3389/fendo.2023.1116582. PMID: 37113491Free PMC Article
Simões JFCPM, Vlaminck S, Seiça RMF, Acke F, Miguéis ACE
Laryngoscope 2023 Jan;133(1):15-24. Epub 2022 Apr 25 doi: 10.1002/lary.30141. PMID: 35467030
Gupta M, Liti B, Barrett C, Thompson PD, Fernandez AB
Am J Med 2022 Jun;135(6):709-714. Epub 2022 Jan 23 doi: 10.1016/j.amjmed.2021.12.006. PMID: 35081380
Wycherley TP, Moran LJ, Clifton PM, Noakes M, Brinkworth GD
Am J Clin Nutr 2012 Dec;96(6):1281-98. Epub 2012 Oct 24 doi: 10.3945/ajcn.112.044321. PMID: 23097268
Singh JA, Reddy SG, Kundukulam J
Curr Opin Rheumatol 2011 Mar;23(2):192-202. doi: 10.1097/BOR.0b013e3283438e13. PMID: 21285714Free PMC Article

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