Gaucher Disease, Type Iii

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OMIM 57 231000 Disease Ontology 12 DOID:0110959 ICD10 33 E75.2 Orphanet 59 ORPHA77261 UMLS via Orphanet 74 C0268251

ICD10 via Orphanet 34 E75.2 MedGen 42 C0268251 C1856491 C1856492 C1856493 more MeSH 44 D005776 SNOMED-CT via HPO 69 258211005 29738008 128602000 22066006 16110005 21061000119107 35489007 78667006 52448006 34436003 53298000 123526007 400003000 85102008 22325002 81308009 127324008 17450006 373945007 16294009 276508000 302215000 415116008 127034005 165397008 271737000 11399002 697898008 70995007 192992007 267581004 37356005 80515008 312444006 12584003 123983008 203522001 30425001 237836003 161832001 248342006 262285001 89362005 250978003 473372009 237897009 233703007 127388009 129646001 240196003 398199007 72756009 49347007 248274002 84229001 more UMLS 73 C0268251 C0268250

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 77261Disease definitionGaucher 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).EpidemiologyThe 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 descriptionThe 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.EtiologyGD 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 methodsDiagnostic 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 counselingTransmission is autosomal recessive.Management and treatmentThe 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.PrognosisIn 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 ii and gaucher's disease, and has symptoms including apnea, muscle rigidity and muscle spasticity. An important gene associated with Gaucher Disease, Type Iii is GBA (Glucosylceramidase Beta), and among its related pathways/superpathways are Sphingolipid metabolism and Lysosome. The drugs Miglustat and 1-Deoxynojirimycin have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and liver, and related phenotypes are ataxia and gait disturbance

OMIM : ⁵⁷ 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 : ⁷⁵ 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.

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.

Wikipedia : ⁷⁶ Gaucher\'s disease or Gaucher disease (/ɡoʊˈʃeɪ/) (GD) is a genetic disorder in which glucocerebroside... 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.