Gaucher Disease, Type Iii (GD3)

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Disease Ontology 12 DOID:0110959 OMIM 56 231000 MeSH 43 D005776 ICD10 32 E75.2 ICD10 via Orphanet 33 E75.2

UMLS via Orphanet 72 C0268251 Orphanet 58 ORPHA77261 MedGen 41 C0268251 C1856491 C1856492 C1856493 more SNOMED-CT via HPO 68 11399002 123526007 123983008 12584003 127034005 127324008 127388009 128602000 129646001 16110005 161832001 16294009 165397008 17450006 192992007 203522001 21061000119107 22066006 22325002 233703007 237836003 237897009 240196003 248274002 248342006 250978003 258211005 262285001 267581004 271737000 276508000 29738008 302215000 30425001 312444006 34436003 35489007 37356005 373945007 398199007 400003000 415116008 473372009 49347007 52448006 53298000 697898008 70995007 72756009 78667006 80515008 81308009 84229001 85102008 89362005 more UMLS 71 C0268250 C0268251

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 77261 Definition Gaucher disease type 3 is the subacute neurological form of Gaucher disease (GD; see this term) characterized by progressive encephalopathy and associated with the systemic manifestations (organomegaly, bone involvement, cytopenia) of GD type 1 (see this term). Epidemiology The annual incidence of GD is about 1/60,000 and the prevalence is approximately 1/100,000. GD type 3 accounts for 5% of all patients with GD. Clinical description The clinical presentation is very heterogeneous. Neurological disease appears in childhood or adolescence, a much later onset than in GD type 2 (see this term). Encephalopathy can be the presenting sign of the disease or may occur later in the disease course. Some patients have moderate systemic involvement associated with ophthalmoplegia as the only neurological symptom. For the more severe forms, the neurological signs encountered are variable: supranuclear horizontal ophthalmoplegia, progressive myoclonic epilepsy , cerebellar ataxia , spasticity and dementia . GD type 3 is also associated with the clinical and biological signs of ''systemic'' disease, such as frequent asthenia, growth retardation or delayed puberty, splenomegaly and hepatomegaly. Bone anomalies may also be present and manifest as deformations, osteopenia, which sometimes leads to pathological fractures or vertebral compression, bone infarctions or even aseptic osteonecrosis. Involvement of other organs (rarely symptomatic pulmonary, renal and cardiac) is less common. Pancytopenia is frequent and involves varying degrees of thrombocytopenia (sometimes severe), anemia and, less frequently, leukoneutropenia. Polyclonal hypergammaglobulinemia is often present and is sometimes complicated by monoclonal gammapathy. Etiology GD type 3 is a lysosomal storage disease caused by a mutation in the GBA gene (1q21) that codes for the lysosomal enzyme , glucocerebrosidase. The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramidase (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, spleen and the bone marrow (Gaucher cells). Diagnostic methods Diagnostic methods involve ultrasound and magnetic resonance imaging (MRI) for initial evaluation and subsequent monitoring of hepatosplenomegaly , radiography and bone scintigraphy to detect bone lesions and complications, osteodensitometry for the evaluation of osteopenia of the lumbar spine and femoral neck, and cardiac ultrasound for the detection of pulmonary arterial hypertension . An increase in certain biological markers that are important both for the initial diagnosis and monitoring with or without treatment, is also observed: chitotriosidase, an angiotensin converting enzyme, ferritin and tartrate-resistant acid phosphatases. Diagnosis can be confirmed by demonstrating a deficit in the enzymatic activity of glucocerebrosidase in circulating leukocytes . In rare cases, genotyping may be of prognostic value: a patient with a homozygous L444P mutation in the GBA gene has a very high risk of developing neurological disease. Genetic counseling Transmission is autosomal recessive . Management and treatment The treatment for patients with GD type 3 exhibiting clinically significant non neurological manifestations is enzyme substitution therapy (imiglucerase with marketing authorization (MA) since 1997). It appears to slow progression of the neurological symptoms and is effective against the systemic manifestations. Prognosis In the absence of treatment, clinical progression leads to death within a few years. Visit the Orphanet disease page for more resources.

MalaCards based summary : Gaucher Disease, Type Iii, also known as gaucher disease, subacute neuronopathic type, is related to gaucher disease, type i and gaucher's disease, and has symptoms including seizures, ataxia and apnea. An important gene associated with Gaucher Disease, Type Iii is GBA (Glucosylceramidase Beta). The drugs Eliglustat and Pharmaceutical Solutions have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and spleen, and related phenotypes are splenomegaly and hepatomegaly

Disease Ontology : ¹² A Gaucher's disease characterized by later onset and slower progession of neurological deterioration compared to type II that has material basis in an autosomal recessive mutation of GBA on chromosome 1q22.

OMIM : ⁵⁶ Gaucher disease type III 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. (231000)

UniProtKB/Swiss-Prot : ⁷³ Gaucher disease 3: A subacute form of neuronopathic Gaucher disease. It has later onset and slower progression compared to the acute form of neuronopathic Gaucher disease 2.

Wikipedia : ⁷⁴ Gaucher's disease or Gaucher disease (/ɡoʊˈʃeɪ/) (GD) is a genetic disorder in which glucocerebroside (a... more...

Clinical features from OMIM:

231000

Search NIH Clinical Center for Gaucher Disease, Type Iii

Search GEO for disease gene expression data for Gaucher Disease, Type Iii.