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Gaucher disease type III(GD3)

MedGen UID:
78653
Concept ID:
C0268251
Disease or Syndrome
Synonyms: Gaucher Disease Type 3 (Subacute/Chronic); Gaucher disease, chronic neuronopathic type; Gaucher disease, juvenile and adult, cerebral; Gaucher disease, subacute neuronopathic type; Gaucher Disease, Type 3; GD 3; GD III; Subacute neuronopathic Gaucher's disease
SNOMED CT: Subacute neuronopathic Gaucher's disease (5963005); Juvenile Gaucher's disease (5963005); Glucosylceramidase deficiency, subacute type (5963005); Gaucher's disease, type III (5963005); Norrbottnian Gaucher disease (5963005); Subacute neuronopathic Gaucher disease (5963005); Juvenile Gaucher disease (5963005); Glucocerebrosidase deficiency type III (5963005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): GBA1 (1q22)
 
Monarch Initiative: MONDO:0009267
OMIM®: 231000
Orphanet: ORPHA77261

Disease characteristics

Excerpted from the GeneReview: Gaucher Disease
Gaucher disease (GD) encompasses a continuum of clinical findings from a perinatal-lethal disorder to an asymptomatic type. The characterization of three major clinical types (1, 2, and 3) and two clinical forms (perinatal-lethal and cardiovascular) is useful in determining prognosis and management. Cardiopulmonary complications have been described with all the clinical phenotypes, although varying in frequency and severity. Type 1 GD is characterized by the presence of clinical or radiographic evidence of bone disease (osteopenia, focal lytic or sclerotic lesions, and osteonecrosis), hepatosplenomegaly, anemia, thrombocytopenia, lung disease, and the absence of primary central nervous system disease. Type 2 GD is characterized by primary central nervous system disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years. Type 3 GD is characterized by primary central nervous system disease with childhood onset, a more slowly progressive course, and survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. [from GeneReviews]
Authors:
Derralynn A Hughes  |  Gregory M Pastores   view full author information

Additional descriptions

From OMIM
Gaucher disease type III (GD3) is the subacute form of neuronopathic Gaucher disease. It has later onset and slower progression compared to the acute form of neuronopathic Gaucher disease, type II. Patterson et al. (1993) suggested that there are 2 phenotypic subgroups of Gaucher disease type III: type IIIA, which is characterized by myoclonus and dementia, and type IIIB, characterized by early onset of isolated horizontal supranuclear gaze palsy and aggressive systemic disease. See also Gaucher disease type IIIC (231005), which is associated with cardiovascular calcifications.  http://www.omim.org/entry/231000
From MedlinePlus Genetics
Gaucher disease is an inherited disorder that affects many of the body's organs and tissues. The signs and symptoms of this condition vary widely among affected individuals. Researchers have described several types of Gaucher disease based on their characteristic features.

Type 1 Gaucher disease is the most common form of this condition. Type 1 is also called non-neuronopathic Gaucher disease because the brain and spinal cord (the central nervous system) are usually not affected. The features of this condition range from mild to severe and may appear anytime from childhood to adulthood. Major signs and symptoms include enlargement of the liver and spleen (hepatosplenomegaly), a low number of red blood cells (anemia), easy bruising caused by a decrease in blood platelets (thrombocytopenia), bone abnormalities such as bone pain and fractures, and joint conditions such as arthritis.

Another form of Gaucher disease is known as the cardiovascular type (or type 3c) because it primarily affects the heart, causing the heart valves to harden (calcify). People with the cardiovascular form of Gaucher disease may also have eye abnormalities, bone disease, and mild enlargement of the spleen (splenomegaly).

Types 2 and 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by problems that affect the central nervous system. In addition to the signs and symptoms described above, these conditions can cause abnormal eye movements, seizures, and brain damage. Type 2 Gaucher disease usually causes life-threatening medical problems beginning in infancy. Type 3 Gaucher disease also affects the nervous system, but it tends to worsen more slowly than type 2.

The most severe type of Gaucher disease is a very rare form of type 2 called the perinatal lethal form. This condition causes severe or life-threatening complications starting before birth or in infancy. Features of the perinatal lethal form can include extensive swelling caused by fluid accumulation before birth (hydrops fetalis); dry, scaly skin (ichthyosis) or other skin abnormalities; hepatosplenomegaly; distinctive facial features; and serious neurological problems. As its name indicates, most infants with the perinatal lethal form of Gaucher disease survive for only a few days after birth.  https://medlineplus.gov/genetics/condition/gaucher-disease

Clinical features

From HPO
Vascular calcification
MedGen UID:
90990
Concept ID:
C0342649
Disease or Syndrome
Abnormal calcification of the vasculature.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Decreased body weight
MedGen UID:
1806755
Concept ID:
C5574742
Finding
Abnormally low body weight.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Spastic paraparesis
MedGen UID:
52432
Concept ID:
C0037771
Sign or Symptom
Mild or moderate loss of motor function accompanied by spasticity in the lower extremities. This condition is a manifestation of CENTRAL NERVOUS SYSTEM DISEASES that cause injury to the motor cortex or descending motor pathways.
Abnormality of speech or vocalization
MedGen UID:
11531
Concept ID:
C0037822
Disease or Syndrome
Abnormalities in the sound of a person's speech or vocalization are not necessarily associated with a known physical cause or due to stuttering or stammering.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
Generalized myoclonic seizure
MedGen UID:
892704
Concept ID:
C4021759
Disease or Syndrome
A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Decreased beta-glucocerebrosidase level
MedGen UID:
1684763
Concept ID:
C5139035
Finding
Reduced level of the enzyme beta-glucosidase, an enzyme that catalyzes the hydrolysis of glucosylceramide into ceramide and glucose.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Horizontal supranuclear gaze palsy
MedGen UID:
870350
Concept ID:
C4024794
Disease or Syndrome
A supranuclear gaze palsy is an inability to look in a horizontal direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.

Term Hierarchy

Recent clinical studies

Etiology

Mohamed YSA, Zayet MK, Omar OM, El-Beshlawy AM
Eur Arch Paediatr Dent 2020 Apr;21(2):241-247. Epub 2019 Sep 17 doi: 10.1007/s40368-019-00471-3. PMID: 31531808
Hopf S, Pfeiffer N, Liesenfeld M, Mengel KE, Hennermann JB, Schmidtmann I, Pitz S
Orphanet J Rare Dis 2019 Nov 14;14(1):257. doi: 10.1186/s13023-019-1244-9. PMID: 31727115Free PMC Article
Djordjević M, Minić P, Sarajlija A, Djuricic SM, Djokić D, Marković O
Vojnosanit Pregl 2011 Dec;68(12):1071-4. PMID: 22352271
Erikson A, Karlberg J, Skogman AL, Dreborg S
Pediatr Neurol 1987 Mar-Apr;3(2):87-91. doi: 10.1016/0887-8994(87)90033-6. PMID: 3508057
Dreborg S, Erikson A, Hagberg B
Eur J Pediatr 1980 Mar;133(2):107-18. doi: 10.1007/BF00441578. PMID: 7363908

Diagnosis

Jezela-Stanek A, Chorostowska-Wynimko J, Tylki-Szymańska A
Clin Respir J 2020 May;14(5):422-429. Epub 2020 Jan 22 doi: 10.1111/crj.13150. PMID: 31912638
Hopf S, Pfeiffer N, Liesenfeld M, Mengel KE, Hennermann JB, Schmidtmann I, Pitz S
Orphanet J Rare Dis 2019 Nov 14;14(1):257. doi: 10.1186/s13023-019-1244-9. PMID: 31727115Free PMC Article
Dahl N, Wadelius C, Annerén G, Gustavson KH
Prenat Diagn 1992 Jul;12(7):603-8. doi: 10.1002/pd.1970120706. PMID: 1508850
Blom S, Erikson A
Eur J Pediatr 1983 Sep;140(4):316-22. doi: 10.1007/BF00442672. PMID: 6628452
Dreborg S, Erikson A, Hagberg B
Eur J Pediatr 1980 Mar;133(2):107-18. doi: 10.1007/BF00441578. PMID: 7363908

Therapy

Dobbelaere D, Sukno S, Defoort-Dhellemmes S, Lamblin MD, Largillière C
J Inherit Metab Dis 1998 Feb;21(1):74-6. doi: 10.1023/a:1005319632539. PMID: 9501273
Bosman DK, Hollak CE, Aerts JM, Bakker HD
J Inherit Metab Dis 1996;19(5):703-4. doi: 10.1007/BF01799852. PMID: 8892032

Prognosis

Dobbelaere D, Sukno S, Defoort-Dhellemmes S, Lamblin MD, Largillière C
J Inherit Metab Dis 1998 Feb;21(1):74-6. doi: 10.1023/a:1005319632539. PMID: 9501273
Erikson A, Karlberg J, Skogman AL, Dreborg S
Pediatr Neurol 1987 Mar-Apr;3(2):87-91. doi: 10.1016/0887-8994(87)90033-6. PMID: 3508057
Dreborg S, Erikson A, Hagberg B
Eur J Pediatr 1980 Mar;133(2):107-18. doi: 10.1007/BF00441578. PMID: 7363908

Clinical prediction guides

Jezela-Stanek A, Chorostowska-Wynimko J, Tylki-Szymańska A
Clin Respir J 2020 May;14(5):422-429. Epub 2020 Jan 22 doi: 10.1111/crj.13150. PMID: 31912638
Hopf S, Pfeiffer N, Liesenfeld M, Mengel KE, Hennermann JB, Schmidtmann I, Pitz S
Orphanet J Rare Dis 2019 Nov 14;14(1):257. doi: 10.1186/s13023-019-1244-9. PMID: 31727115Free PMC Article
Garbutt S, Harris CM
Br J Ophthalmol 2000 May;84(5):451-5. doi: 10.1136/bjo.84.5.451. PMID: 10781506Free PMC Article
Erikson A, Karlberg J, Skogman AL, Dreborg S
Pediatr Neurol 1987 Mar-Apr;3(2):87-91. doi: 10.1016/0887-8994(87)90033-6. PMID: 3508057

Supplemental Content

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    Clinical resources

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    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Decreased ß-glucocerebrosidase, Gaucher disease, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, Gaucher Disease; Decreased beta-glucocerebrosidase activity, 2022

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