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Hyperglycemia

MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome; Finding
Synonym: Hyperglycemias
SNOMED CT: Hyperglycemia (80394007); Hyperglycemic disorder (237598005)
 
HPO: HP:0003074
Monarch Initiative: MONDO:0002909

Definition

An increased concentration of glucose in the blood. [from HPO]

Conditions with this feature

Diabetes mellitus type 1
MedGen UID:
41522
Concept ID:
C0011854
Disease or Syndrome
Type 1 diabetes mellitus (T1D), also designated insulin-dependent diabetes mellitus (IDDM), is a disorder of glucose homeostasis characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classic phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Greig cephalopolysyndactyly syndrome
MedGen UID:
120531
Concept ID:
C0265306
Congenital Abnormality
Typical Greig cephalopolysyndactyly syndrome (GCPS) is characterized by macrocephaly, widely spaced eyes associated with increased interpupillary distance, preaxial polydactyly with or without postaxial polydactyly, and cutaneous syndactyly. Developmental delay, intellectual disability, or seizures appear to be uncommon manifestations (~<10%) of GCPS and may be more common in individuals with large (>300-kb) deletions that encompass GLI3. Approximately 20% of individuals with GCPS have hypoplasia or agenesis of the corpus callosum.
Leprechaunism syndrome
MedGen UID:
82708
Concept ID:
C0265344
Disease or Syndrome
INSR-related severe syndromic insulin resistance comprises a phenotypic spectrum that is a continuum from the severe phenotype Donohue syndrome (DS) (also known as leprechaunism) to the milder phenotype Rabson-Mendenhall syndrome (RMS). DS at the severe end of the spectrum is characterized by severe insulin resistance (hyperinsulinemia with associated fasting hypoglycemia and postprandial hyperglycemia), severe prenatal growth restriction and postnatal growth failure, hypotonia and developmental delay, characteristic facies, and organomegaly involving heart, kidneys, liver, spleen, and ovaries. Death usually occurs before age one year. RMS at the milder end of the spectrum is characterized by severe insulin resistance that, although not as severe as that of DS, is nonetheless accompanied by fluctuations in blood glucose levels, diabetic ketoacidosis, and – in the second decade – microvascular complications. Findings can range from severe growth delay and intellectual disability to normal growth and development. Facial features can be milder than those of DS. Complications of longstanding hyperglycemia are the most common cause of death. While death usually occurs in the second decade, some affected individuals live longer.
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.
Rabson-Mendenhall syndrome
MedGen UID:
78783
Concept ID:
C0271695
Disease or Syndrome
INSR-related severe syndromic insulin resistance comprises a phenotypic spectrum that is a continuum from the severe phenotype Donohue syndrome (DS) (also known as leprechaunism) to the milder phenotype Rabson-Mendenhall syndrome (RMS). DS at the severe end of the spectrum is characterized by severe insulin resistance (hyperinsulinemia with associated fasting hypoglycemia and postprandial hyperglycemia), severe prenatal growth restriction and postnatal growth failure, hypotonia and developmental delay, characteristic facies, and organomegaly involving heart, kidneys, liver, spleen, and ovaries. Death usually occurs before age one year. RMS at the milder end of the spectrum is characterized by severe insulin resistance that, although not as severe as that of DS, is nonetheless accompanied by fluctuations in blood glucose levels, diabetic ketoacidosis, and – in the second decade – microvascular complications. Findings can range from severe growth delay and intellectual disability to normal growth and development. Facial features can be milder than those of DS. Complications of longstanding hyperglycemia are the most common cause of death. While death usually occurs in the second decade, some affected individuals live longer.
Hyperproinsulinemia
MedGen UID:
137967
Concept ID:
C0342283
Disease or Syndrome
Insulin (INS; 176730) is produced posttranslationally from its precursor molecule, proinsulin, by site-directed proteolysis in beta-cell granules. Conversion involves cleavage at pairs of basic residues that link both the insulin A and B chains to C-peptide. Human proinsulin conversion has a preferred sequential route, such that cleavage at the B-chain/C-peptide junction occurs first, producing des-31,32 split proinsulin as the major conversion intermediate. Under normal circumstances, proinsulin conversion is largely completed before secretion, and low plasma levels of intact proinsulin and conversion intermediates are found. Structural abnormalities in the proinsulin molecule can impair conversion, leading to the accumulation of proinsulin-like material in the circulation. Such defects show an autosomal dominant mode of inheritance and are the main cause of familial hyperproinsulinemia (summary by Warren-Perry et al., 1997).
Diabetes-deafness syndrome maternally transmitted
MedGen UID:
90979
Concept ID:
C0342289
Disease or Syndrome
Maternally inherited diabetes-deafness syndrome (MIDD) is a mitochondrial disorder characterized by onset of sensorineural hearing loss and diabetes in adulthood. Some patients may have additional features observed in mitochondrial disorders, including pigmentary retinopathy, ptosis, cardiomyopathy, myopathy, renal problems, and neuropsychiatric symptoms (Ballinger et al., 1992; Reardon et al., 1992; Guillausseau et al., 2001). The association of diabetes and deafness is observed with Wolfram syndrome (see 222300), Rogers syndrome (249270), and Herrmann syndrome (172500), but all 3 of these disorders have other clinical manifestations.
SHORT syndrome
MedGen UID:
164212
Concept ID:
C0878684
Disease or Syndrome
SHORT syndrome is a mnemonic for short stature, hyperextensibility, ocular depression (deeply set eyes), Rieger anomaly, and teething delay. It is now recognized that the features most consistently observed in SHORT syndrome are mild intrauterine growth restriction (IUGR); mild to moderate short stature; partial lipodystrophy (evident in the face, and later in the chest and upper extremities, often sparing the buttocks and legs); and a characteristic facial gestalt. Insulin resistance may be evident in mid-childhood or adolescence, although diabetes mellitus typically does not develop until early adulthood. Other frequent features include Axenfeld-Rieger anomaly or related ocular anterior chamber dysgenesis, delayed dentition and other dental issues, and sensorineural hearing loss.
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.
Diabetes mellitus, transient neonatal, 1
MedGen UID:
371317
Concept ID:
C1832386
Disease or Syndrome
6q24-related transient neonatal diabetes mellitus (6q24-TNDM) is defined as transient neonatal diabetes mellitus caused by genetic aberrations of the imprinted locus at 6q24. The cardinal features are: severe intrauterine growth retardation, hyperglycemia that begins in the neonatal period in a term infant and resolves by age 18 months, dehydration, and absence of ketoacidosis. Macroglossia and umbilical hernia may be present. 6q24-TNDM associated with a multilocus imprinting disturbance (MLID) can be associated with marked hypotonia, congenital heart disease, deafness, neurologic features including epilepsy, and renal malformations. Diabetes mellitus usually starts within the first week of life and lasts on average three months but can last longer than a year. Although insulin is usually required initially, the need for insulin gradually declines over time. Intermittent episodes of hyperglycemia may occur in childhood, particularly during intercurrent illnesses. Diabetes mellitus may recur in adolescence or later in adulthood. Women who have had 6q24-TNDM are at risk for relapse during pregnancy.
Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome
MedGen UID:
332288
Concept ID:
C1836780
Disease or Syndrome
Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome is characterized by neonatal diabetes mellitus associated with cerebellar and/or pancreatic agenesis.
Mandibuloacral dysplasia with type B lipodystrophy
MedGen UID:
332940
Concept ID:
C1837756
Disease or Syndrome
Mandibuloacral dysplasia with type B lipodystrophy (MADB) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies such as mandibular hypoplasia, skeletal anomalies such as progressive osteolysis of the terminal phalanges and clavicles, and skin changes such as mottled hyperpigmentation and atrophy. The lipodystrophy is characterized by generalized loss of subcutaneous fat involving the face, trunk, and extremities. Some patients have a progeroid appearance. Metabolic complications associated with insulin resistance have been reported (Schrander-Stumpel et al., 1992; summary by Simha et al., 2003). For a general phenotypic description of lipodystrophy associated with mandibuloacral dysplasia, see MADA (248370).
Maturity-onset diabetes of the young type 3
MedGen UID:
324942
Concept ID:
C1838100
Disease or Syndrome
MODY is a form of familial noninsulin-dependent diabetes mellitus (T2D; 125853) and is characterized by an early age of onset (childhood, adolescence, or young adulthood under 25 years) and autosomal dominant inheritance. For a phenotypic description and discussion of genetic heterogeneity of MODY, see 606391.
Male hypergonadotropic hypogonadism-intellectual disability-skeletal anomalies syndrome
MedGen UID:
334557
Concept ID:
C1843994
Disease or Syndrome
This syndrome is characterized by hypergonadotropic hypogonadism, intellectual deficit, congenital skeletal anomalies involving the cervical spine and superior ribs, and diabetes mellitus.
Maturity-onset diabetes of the young type 8
MedGen UID:
342845
Concept ID:
C1853297
Disease or Syndrome
Maturity-onset diabetes of the young type 8 (MODY8) is characterized by onset of diabetes before age 25 years, with slowly progressive pancreatic exocrine dysfunction, fatty replacement of pancreatic parenchyma (lipomatosis), and development of pancreatic cysts. Patients do not present clinical signs of chronic pancreatitis (summary by Johansson et al., 2018). For a phenotypic description and discussion of genetic heterogeneity of MODY, see 606391.
Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type
MedGen UID:
387801
Concept ID:
C1857355
Disease or Syndrome
Mitochondrial complex IV deficiency nuclear type 5 (MC4DN5) is an autosomal recessive severe metabolic multisystemic disorder with onset in infancy. Features include delayed psychomotor development, impaired intellectual development with speech delay, mild dysmorphic facial features, hypotonia, ataxia, and seizures. There is increased serum lactate and episodic hypoglycemia. Some patients may have cardiomyopathy, abnormal breathing, or liver abnormalities, reflecting systemic involvement. Brain imaging shows lesions in the brainstem and basal ganglia, consistent with a diagnosis of Leigh syndrome (see 256000). Affected individuals tend to have episodic metabolic and/or neurologic crises in early childhood, which often lead to early death (summary by Debray et al., 2011). For a discussion of genetic heterogeneity of mitochondrial complex IV (cytochrome c oxidase) deficiency, see 220110.
Hereditary motor and sensory neuropathy, Okinawa type
MedGen UID:
346886
Concept ID:
C1858338
Disease or Syndrome
Okinawa-type hereditary motor and sensory neuropathy (HMSNO) is an autosomal dominant neurodegenerative disorder characterized by young adult onset of proximal or distal muscle weakness and atrophy, muscle cramps, and fasciculations, with later onset of distal sensory impairment. The disorder is slowly progressive and clinically resembles amyotrophic lateral sclerosis (ALS; see 105400) (summary by Ishiura et al., 2012).
Bardet-Biedl syndrome 9
MedGen UID:
347182
Concept ID:
C1859567
Disease or Syndrome
BBS9 is an autosomal recessive disorder characterized by obesity, polydactyly, renal anomalies, retinopathy, and mental retardation (Abu-Safieh et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Diabetes mellitus, transient neonatal, 3
MedGen UID:
351177
Concept ID:
C1864623
Disease or Syndrome
Any transient neonatal diabetes mellitus in which the cause of the disease is a mutation in the KCNJ11 gene.
Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome
MedGen UID:
411637
Concept ID:
C2748662
Disease or Syndrome
Mitchell-Riley syndrome is characterized by neonatal diabetes, pancreatic hypoplasia, intestinal atresia, and gallbladder aplasia or hypoplasia. There is considerable phenotypic overlap between Mitchell-Riley syndrome and Martinez-Frias syndrome (601346), the latter being characterized by the features of the Mitchell-Riley syndrome except for neonatal diabetes, and including tracheoesophageal fistula in some patients (Smith et al., 2010).
Maturity-onset diabetes of the young type 10
MedGen UID:
461967
Concept ID:
C3150617
Disease or Syndrome
HNF1A-MODY and HNF4A-MODY have similar signs and symptoms that develop slowly over time. Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time uncontrolled high blood glucose can damage small blood vessels in the eyes and kidneys. Damage to the light-sensitive tissue at the back of the eye (the retina) causes a condition known as diabetic retinopathy that can lead to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) can lead to kidney failure and end-stage renal disease (ESRD). While these two types of MODY are very similar, certain features are particular to each type. For example, babies with HNF4A-MODY tend to weigh more than average or have abnormally low blood glucose at birth, even though other signs of the condition do not occur until childhood or young adulthood. People with HNF1A-MODY have a higher-than-average risk of developing noncancerous (benign) liver tumors known as hepatocellular adenomas.\n\nThe different types of MODY are distinguished by their genetic causes. The most common types are HNF1A-MODY (also known as MODY3), accounting for 50 to 70 percent of cases, and GCK-MODY (MODY2), accounting for 30 to 50 percent of cases. Less frequent types include HNF4A-MODY (MODY1) and renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5), which each account for 5 to 10 percent of cases. At least ten other types have been identified, and these are very rare.\n\nGCK-MODY is a very mild type of the condition. People with this type have slightly elevated blood glucose levels, particularly in the morning before eating (fasting blood glucose). However, affected individuals often have no symptoms related to the disorder, and diabetes-related complications are extremely rare.\n\nRCAD is associated with a combination of diabetes and kidney or urinary tract abnormalities (unrelated to the elevated blood glucose), most commonly fluid-filled sacs (cysts) in the kidneys. However, the signs and symptoms are variable, even within families, and not everyone with RCAD has both features. Affected individuals may have other features unrelated to diabetes, such as abnormalities of the pancreas or liver or a form of arthritis called gout.\n\nMaturity-onset diabetes of the young (MODY) is a group of several conditions characterized by abnormally high levels of blood glucose, also called blood sugar. These forms of diabetes typically begin before age 30, although they can occur later in life. In MODY, elevated blood glucose arises from reduced production of insulin, which is a hormone produced in the pancreas that helps regulate blood glucose levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source.
Mitochondrial complex III deficiency nuclear type 1
MedGen UID:
762097
Concept ID:
C3541471
Disease or Syndrome
Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. Many patients die in early childhood, but some may show longer survival (de Lonlay et al., 2001; De Meirleir et al., 2003). Genetic Heterogeneity of Mitochondrial Complex III Deficiency Mitochondrial complex III deficiency can be caused by mutation in several different nuclear-encoded genes. See MC3DN2 (615157), caused by mutation in the TTC19 gene (613814) on chromosome 17p12; MC3DN3 (615158), caused by mutation in the UQCRB gene (191330) on chromosome 8q; MC3DN4 (615159), caused by mutation in the UQCRQ gene (612080) on chromosome 5q31; MC3DN5 (615160), caused by mutation in the UQCRC2 gene (191329) on chromosome 16p12; MC3DN6 (615453), caused by mutation in the CYC1 gene (123980) on chromosome 8q24; MC3DN7 (615824), caused by mutation in the UQCC2 gene (614461) on chromosome 6p21; MC3DN8 (615838), caused by mutation in the LYRM7 gene (615831) on chromosome 5q23; MC3DN9 (616111), caused by mutation in the UQCC3 gene (616097) on chromosome 11q12; and MC3DN10 (618775), caused by mutation in the UQCRFS1 gene (191327) on chromosome 19q12. See also MTYCB (516020) for a discussion of a milder phenotype associated with isolated mitochondrial complex III deficiency and mutations in a mitochondrial-encoded gene.
Mitochondrial complex III deficiency nuclear type 6
MedGen UID:
815883
Concept ID:
C3809553
Disease or Syndrome
Mitochondrial complex III deficiency nuclear type 6 (MC3DN6) is an autosomal recessive disorder caused by mitochondrial dysfunction. It is characterized by onset in early childhood of episodic acute lactic acidosis, ketoacidosis, and insulin-responsive hyperglycemia, usually associated with infection. Laboratory studies show decreased activity of mitochondrial complex III. Psychomotor development is normal (summary by Gaignard et al., 2013). For a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (124000).
Hypopigmentation-punctate palmoplantar keratoderma syndrome
MedGen UID:
816111
Concept ID:
C3809781
Disease or Syndrome
Cole disease is a rare autosomal dominant disorder characterized by congenital or early-onset punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show nonspecific changes including hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer (summary by Eytan et al., 2013). Some patients also exhibit calcinosis cutis or early-onset calcific tendinopathy (Eytan et al., 2013).
Pancreatic hypoplasia-diabetes-congenital heart disease syndrome
MedGen UID:
860891
Concept ID:
C4012454
Congenital Abnormality
A rare, syndromic diabetes mellitus characterized by partial pancreatic agenesis, diabetes mellitus, and heart anomalies (including transposition of the great vessels, ventricular or atrial septal defects, pulmonary stenosis, or patent ductus arteriosis).
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.
ACTH-independent macronodular adrenal hyperplasia 2
MedGen UID:
863240
Concept ID:
C4014803
Disease or Syndrome
ACTH-independent macronodular adrenal hyperplasia-2 is an autosomal dominant tumor susceptibility with syndromic incomplete penetrance, as a second hit to the ARMC5 gene is required to develop macronodular hyperplasia (Assie et al., 2013).
Maturity-onset diabetes of the young type 13
MedGen UID:
897640
Concept ID:
C4225365
Disease or Syndrome
Maturity-onset diabetes of the young (MODY) is a group of several conditions characterized by abnormally high levels of blood glucose, also called blood sugar. These forms of diabetes typically begin before age 30, although they can occur later in life. In MODY, elevated blood glucose arises from reduced production of insulin, which is a hormone produced in the pancreas that helps regulate blood glucose levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source.\n\nRCAD is associated with a combination of diabetes and kidney or urinary tract abnormalities (unrelated to the elevated blood glucose), most commonly fluid-filled sacs (cysts) in the kidneys. However, the signs and symptoms are variable, even within families, and not everyone with RCAD has both features. Affected individuals may have other features unrelated to diabetes, such as abnormalities of the pancreas or liver or a form of arthritis called gout.\n\nGCK-MODY is a very mild type of the condition. People with this type have slightly elevated blood glucose levels, particularly in the morning before eating (fasting blood glucose). However, affected individuals often have no symptoms related to the disorder, and diabetes-related complications are extremely rare.\n\nThe different types of MODY are distinguished by their genetic causes. The most common types are HNF1A-MODY (also known as MODY3), accounting for 50 to 70 percent of cases, and GCK-MODY (MODY2), accounting for 30 to 50 percent of cases. Less frequent types include HNF4A-MODY (MODY1) and renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5), which each account for 5 to 10 percent of cases. At least ten other types have been identified, and these are very rare.\n\nHNF1A-MODY and HNF4A-MODY have similar signs and symptoms that develop slowly over time. Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time uncontrolled high blood glucose can damage small blood vessels in the eyes and kidneys. Damage to the light-sensitive tissue at the back of the eye (the retina) causes a condition known as diabetic retinopathy that can lead to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) can lead to kidney failure and end-stage renal disease (ESRD). While these two types of MODY are very similar, certain features are particular to each type. For example, babies with HNF4A-MODY tend to weigh more than average or have abnormally low blood glucose at birth, even though other signs of the condition do not occur until childhood or young adulthood. People with HNF1A-MODY have a higher-than-average risk of developing noncancerous (benign) liver tumors known as hepatocellular adenomas.
Permanent neonatal diabetes mellitus 1
MedGen UID:
1717586
Concept ID:
C5393570
Disease or Syndrome
Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to 26 weeks). The diabetes mellitus is associated with partial or complete insulin deficiency. Clinical manifestations at the time of diagnosis include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Therapy with insulin corrects the hyperglycemia and results in dramatic catch-up growth. The course of PNDM varies by genotype.
Diabetes mellitus, permanent neonatal 2
MedGen UID:
1713823
Concept ID:
C5394296
Disease or Syndrome
Permanent neonatal diabetes mellitus-2 (PNDM2) is characterized by onset of insulin-requiring hyperglycemia within the first months of life that requires insulin therapy throughout life. Some patients additionally have marked developmental delay, muscle weakness, and epilepsy (Gloyn et al., 2004). The triad of developmental delay, epilepsy, and neonatal diabetes is known as DEND (Shimomura et al., 2007). Proks et al. (2006) stated that heterozygous activating mutations in KCNJ11 are the most common cause of PNDM and account for 26 to 64% of cases, and that neurologic features are found in 20% of patients with KCNJ11 mutations. For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176).
Diabetes mellitus, permanent neonatal 3
MedGen UID:
1717271
Concept ID:
C5394303
Disease or Syndrome
Permanent neonatal diabetes mellitus-3 (PNDM3) is characterized by the onset of mild to severe hyperglycemia within the first months of life, and requires lifelong therapy (summary by Babenko et al., 2006). Some patients also have neurologic features, including developmental delay and epilepsy (Proks et al., 2006; Babenko et al., 2006). The triad of developmental delay, epilepsy, and neonatal diabetes is known as DEND. For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176).
Diabetes mellitus, permanent neonatal 4
MedGen UID:
1711191
Concept ID:
C5394307
Disease or Syndrome
Permanent neonatal diabetes mellitus-4 (PNDM4) is characterized by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life (summary by Polak et al., 2008). For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176).
Mandibuloacral dysplasia with type A lipodystrophy
MedGen UID:
1757618
Concept ID:
C5399785
Disease or Syndrome
Mandibuloacral dysplasia with type A lipodystrophy (MADA) is an autosomal recessive disorder characterized by growth retardation, craniofacial anomalies with mandibular hypoplasia, skeletal abnormalities with progressive osteolysis of the distal phalanges and clavicles, and pigmentary skin changes. The lipodystrophy is characterized by a marked acral loss of fatty tissue with normal or increased fatty tissue in the neck and trunk. Some patients may show progeroid features. Metabolic complications can arise due to insulin resistance and diabetes (Young et al., 1971; Simha and Garg, 2002; summary by Garavelli et al., 2009). See also MAD type B (MADB; 608612), which is caused by mutation in the ZMPSTE24 gene (606480).
Cone-rod synaptic disorder syndrome, congenital nonprogressive
MedGen UID:
1773574
Concept ID:
C5436505
Disease or Syndrome
Congenital nonprogressive cone-rod synaptic disorder syndrome (CRSDS) is characterized by retinal and neurodevelopmental disease as well as occasional anomalies of glucose homeostasis. Patients exhibit low vision, photophobia, and nystagmus, and show an electronegative waveform in response to bright flash under dark adaptation on electroretinography, with severely reduced and delayed light-adapted responses. Neurodevelopmental features include poor to no language and autistic behaviors (Mechaussier et al., 2020).
Combined oxidative phosphorylation deficiency 54
MedGen UID:
1812715
Concept ID:
C5676912
Disease or Syndrome
Combined oxidative phosphorylation deficiency-54 (COXPD54) is an autosomal recessive disorder with pleiotropic multisystem presentations resulting from a disruption in mitochondrial transcription and translation. The phenotype is highly variable. Many patients have early-onset sensorineural hearing loss, sometimes in isolation, and sometimes associated with global developmental delay or primary ovarian failure. Other features may include peripheral hypertonia, seizures, muscle weakness, behavioral abnormalities, and leukoencephalopathy on brain imaging. Serum lactate may or may not be elevated (summary by Hochberg et al., 2021). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).

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PubMed

Samsu N
Biomed Res Int 2021;2021:1497449. Epub 2021 Jul 8 doi: 10.1155/2021/1497449. PMID: 34307650Free PMC Article
Lende M, Rijhsinghani A
Int J Environ Res Public Health 2020 Dec 21;17(24) doi: 10.3390/ijerph17249573. PMID: 33371325Free PMC Article
Mayfield J
Am Fam Physician 1998 Oct 15;58(6):1355-62, 1369-70. PMID: 9803200

Recent clinical studies

Etiology

Mifsud S, Schembri EL, Gruppetta M
Br J Hosp Med (Lond) 2018 Nov 2;79(11):634-639. doi: 10.12968/hmed.2018.79.11.634. PMID: 30418830
Wallace MD, Metzger NL
Ann Pharmacother 2018 Jan;52(1):86-90. Epub 2017 Aug 24 doi: 10.1177/1060028017728297. PMID: 28836444
Khazai NB, Hamdy O
Endocrinol Metab Clin North Am 2016 Dec;45(4):875-894. Epub 2016 Oct 6 doi: 10.1016/j.ecl.2016.06.013. PMID: 27823609
Kwon S, Hermayer KL, Hermayer K
Am J Med Sci 2013 Apr;345(4):274-277. doi: 10.1097/MAJ.0b013e31828a6a01. PMID: 23531958
Clore JN, Thurby-Hay L
Endocr Pract 2009 Jul-Aug;15(5):469-74. doi: 10.4158/EP08331.RAR. PMID: 19454391

Diagnosis

Tosur M, Viau-Colindres J, Astudillo M, Redondo MJ, Lyons SK
BMJ Open Diabetes Res Care 2020 Jan;8(1) doi: 10.1136/bmjdrc-2019-000801. PMID: 31958298Free PMC Article
Chowdhury TA
Clin Med (Lond) 2019 Sep;19(5):392-395. doi: 10.7861/clinmed.2019-0195. PMID: 31530687Free PMC Article
Duggan EW, Carlson K, Umpierrez GE
Anesthesiology 2017 Mar;126(3):547-560. doi: 10.1097/ALN.0000000000001515. PMID: 28121636Free PMC Article
Perez A, Jansen-Chaparro S, Saigi I, Bernal-Lopez MR, Miñambres I, Gomez-Huelgas R
J Diabetes 2014 Jan;6(1):9-20. Epub 2013 Oct 29 doi: 10.1111/1753-0407.12090. PMID: 24103089
Clore JN, Thurby-Hay L
Endocr Pract 2009 Jul-Aug;15(5):469-74. doi: 10.4158/EP08331.RAR. PMID: 19454391

Therapy

Battelino T, Alexander CM, Amiel SA, Arreaza-Rubin G, Beck RW, Bergenstal RM, Buckingham BA, Carroll J, Ceriello A, Chow E, Choudhary P, Close K, Danne T, Dutta S, Gabbay R, Garg S, Heverly J, Hirsch IB, Kader T, Kenney J, Kovatchev B, Laffel L, Maahs D, Mathieu C, Mauricio D, Nimri R, Nishimura R, Scharf M, Del Prato S, Renard E, Rosenstock J, Saboo B, Ueki K, Umpierrez GE, Weinzimer SA, Phillip M
Lancet Diabetes Endocrinol 2023 Jan;11(1):42-57. Epub 2022 Dec 6 doi: 10.1016/S2213-8587(22)00319-9. PMID: 36493795
Yamazaki T, Mimura I, Tanaka T, Nangaku M
Diabetes Metab J 2021 Jan;45(1):11-26. Epub 2021 Jan 22 doi: 10.4093/dmj.2020.0217. PMID: 33508907Free PMC Article
Gilbert MP, Pratley RE
Front Endocrinol (Lausanne) 2020;11:178. Epub 2020 Apr 3 doi: 10.3389/fendo.2020.00178. PMID: 32308645Free PMC Article
Gunst J, De Bruyn A, Van den Berghe G
Curr Opin Anaesthesiol 2019 Apr;32(2):156-162. doi: 10.1097/ACO.0000000000000706. PMID: 30817388Free PMC Article
Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS
N Engl J Med 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949. PMID: 28467880Free PMC Article

Prognosis

Shen S, Chen Y, Carpio A, Chang C, Iyengar NM
Cancer 2023 Dec 15;129(24):3854-3861. Epub 2023 Sep 25 doi: 10.1002/cncr.34928. PMID: 37743730Free PMC Article
Richter B, Hemmingsen B, Metzendorf MI, Takwoingi Y
Cochrane Database Syst Rev 2018 Oct 29;10(10):CD012661. doi: 10.1002/14651858.CD012661.pub2. PMID: 30371961Free PMC Article
Hermans G, Van den Berghe G
Crit Care 2015 Aug 5;19(1):274. doi: 10.1186/s13054-015-0993-7. PMID: 26242743Free PMC Article
Kwon S, Hermayer KL, Hermayer K
Am J Med Sci 2013 Apr;345(4):274-277. doi: 10.1097/MAJ.0b013e31828a6a01. PMID: 23531958
Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R
Endocr Relat Cancer 2009 Dec;16(4):1103-23. Epub 2009 Jul 20 doi: 10.1677/ERC-09-0087. PMID: 19620249

Clinical prediction guides

Wang Y, Yang P, Yan Z, Liu Z, Ma Q, Zhang Z, Wang Y, Su Y
J Diabetes Res 2021;2021:6656062. Epub 2021 Feb 25 doi: 10.1155/2021/6656062. PMID: 33728350Free PMC Article
Pappas C, Kandaraki EA, Tsirona S, Kountouras D, Kassi G, Diamanti-Kandarakis E
Hormones (Athens) 2016 Jul;15(3):321-344. doi: 10.14310/horm.2002.1697. PMID: 27838603
Voormolen DN, Abell SK, James R, Hague WM, Mol BW
Semin Reprod Med 2016 Mar;34(2):102-9. Epub 2016 Feb 11 doi: 10.1055/s-0036-1572440. PMID: 26866601
Khater N, Khauli R
Urol Int 2013;90(4):373-80. Epub 2012 Oct 19 doi: 10.1159/000342965. PMID: 23095211
Duncan AE
Curr Pharm Des 2012;18(38):6195-203. doi: 10.2174/138161212803832236. PMID: 22762467Free PMC Article

Recent systematic reviews

Valaiyapathi B, Gower B, Ashraf AP
Curr Diabetes Rev 2020;16(3):220-229. doi: 10.2174/1573399814666180608074510. PMID: 29879890Free PMC Article
Immanuel J, Simmons D
Curr Diab Rep 2017 Oct 2;17(11):115. doi: 10.1007/s11892-017-0943-7. PMID: 28971305
Mauri-Obradors E, Estrugo-Devesa A, Jané-Salas E, Viñas M, López-López J
Med Oral Patol Oral Cir Bucal 2017 Sep 1;22(5):e586-e594. doi: 10.4317/medoral.21655. PMID: 28809366Free PMC Article
Farrar D, Simmonds M, Bryant M, Sheldon TA, Tuffnell D, Golder S, Dunne F, Lawlor DA
BMJ 2016 Sep 13;354:i4694. doi: 10.1136/bmj.i4694. PMID: 27624087Free PMC Article
Martin ET, Kaye KS, Knott C, Nguyen H, Santarossa M, Evans R, Bertran E, Jaber L
Infect Control Hosp Epidemiol 2016 Jan;37(1):88-99. Epub 2015 Oct 27 doi: 10.1017/ice.2015.249. PMID: 26503187Free PMC Article

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