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Gaucher disease type I(GD1)

MedGen UID:
409531
Concept ID:
C1961835
Disease or Syndrome
Synonyms: Acid beta-glucosidase deficiency; Gaucher disease type 1; Gaucher disease, noncerebral juvenile; Gaucher's disease, type 1; GBA DEFICIENCY; GD 1; GD I; GD1; Glucocerebrosidase deficiency
SNOMED CT: Gaucher's disease, type I (62201009); Noncerebral juvenile Gaucher's disease (62201009); Glucocerebrosidase deficiency type I (62201009)
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:0009265
OMIM®: 230800
Orphanet: ORPHA77259

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 (GD) is an autosomal recessive lysosomal storage disorder due to deficient activity of beta-glucocerebrosidase. As a result of this deficiency, there is intracellular accumulation of glucosylceramide (GlcCer, glucosylcerebroside) primarily within cells of mononuclear phagocyte origin, which are the characteristic 'Gaucher cells' identified in most tissues (Jmoudiak and Futerman, 2005). Gaucher disease is classically categorized phenotypically into 3 main subtypes: nonneuronopathic type I (GD1), acute neuronopathic type II (GD2; 230900), and subacute neuronopathic type III (GD3; 231000). Type I is the most common form of Gaucher disease and lacks primary central nervous system involvement. Types II and III have central nervous system involvement and neurologic manifestations (Knudson and Kaplan, 1962; Jmoudiak and Futerman, 2005). All 3 forms of Gaucher disease are caused by mutation in the GBA gene. There are 2 additional phenotypes that may be distinguished: perinatal lethal Gaucher disease (608013), which is a severe form of type II, and Gaucher disease type IIIC (231005), which also has cardiovascular calcifications. See also 610539 for a form of atypical Gaucher disease caused by mutation in the gene encoding saposin C (PSAP; 176801), which is an activator of beta-glucosidase.  http://www.omim.org/entry/230800
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.

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.

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).  https://medlineplus.gov/genetics/condition/gaucher-disease

Clinical features

From HPO
Bone pain
MedGen UID:
57489
Concept ID:
C0151825
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.
Multiple myeloma
MedGen UID:
10122
Concept ID:
C0026764
Neoplastic Process
Multiple myeloma is a neoplastic plasma cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment, monoclonal protein in the blood or urine, and associated organ dysfunction (Palumbo and Anderson, 2011).
Erlenmeyer flask deformity of the femurs
MedGen UID:
383796
Concept ID:
C1855895
Finding
Flaring of distal femur.
Aortic valve stenosis
MedGen UID:
1621
Concept ID:
C0003507
Pathologic Function
The presence of a stenosis (narrowing) of the aortic valve.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Mitral regurgitation
MedGen UID:
7670
Concept ID:
C0026266
Disease or Syndrome
An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
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.
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Avascular necrosis
MedGen UID:
10200
Concept ID:
C0027543
Disease or Syndrome
A disease where there is cellular death (necrosis) of bone components due to interruption of the blood supply.
Vertebral compression fracture
MedGen UID:
75497
Concept ID:
C0262431
Finding
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Pulmonary infiltrates
MedGen UID:
116009
Concept ID:
C0235896
Finding
A finding indicating the presence of an inflammatory or neoplastic cellular infiltrate in the lung parenchyma.
Abnormal pulmonary interstitial morphology
MedGen UID:
1788738
Concept ID:
C5441745
Anatomical Abnormality
Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis.
Hypersplenism
MedGen UID:
9372
Concept ID:
C0020532
Disease or Syndrome
A malfunctioning of the spleen in which it prematurely destroys red blood cells.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Hyperpigmentation of the skin
MedGen UID:
57992
Concept ID:
C0162834
Pathologic Function
A darkening of the skin related to an increase in melanin production and deposition.
Macular atrophy
MedGen UID:
140841
Concept ID:
C0423421
Finding
Well-demarcated area(s) of partial or complete depigmentation in the macula, reflecting atrophy of the retinal pigment epithelium with associated retinal photoreceptor loss.
Abnormality of the eye
MedGen UID:
1370071
Concept ID:
C4316870
Anatomical Abnormality
Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Professional guidelines

PubMed

Iaccarino Idelson P, Speranza E, Marra M, Pasanisi F, Sammarco R, Galletti F, Strazzullo P, Barbato A
Nutrients 2022 Aug 3;14(15) doi: 10.3390/nu14153180. PMID: 35956356Free PMC Article
Di Rocco M, Andria G, Bembi B, Carubbi F, Giona F, Giuffrida G, Linari S, Sibilio M, Spina V, Cappellini MD
Mol Genet Metab 2012 Nov;107(3):521-5. Epub 2012 Aug 17 doi: 10.1016/j.ymgme.2012.08.009. PMID: 22954583
Sibille A, Eng CM, Kim SJ, Pastores G, Grabowski GA
Am J Hum Genet 1993 Jun;52(6):1094-101. PMID: 8503443Free PMC Article

Curated

American College of Medical Genetics and Genomics, Algorithm, Gaucher Disease; Decreased beta-glucocerebrosidase activity, 2022

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Decreased ß-glucocerebrosidase, Gaucher disease, 2022

Recent clinical studies

Etiology

Zhang X, Wu Y, Wang L, Wu Q, Liu Q, Li R
Clin Lab 2023 Apr 1;69(4) doi: 10.7754/Clin.Lab.2022.220816. PMID: 37057944
Iaccarino Idelson P, Speranza E, Marra M, Pasanisi F, Sammarco R, Galletti F, Strazzullo P, Barbato A
Nutrients 2022 Aug 3;14(15) doi: 10.3390/nu14153180. PMID: 35956356Free PMC Article
Razek AAKA, Abdalla A, Barakat T, El-Taher H, Ali K
Blood Cells Mol Dis 2018 Feb;68:139-142. Epub 2016 Dec 20 doi: 10.1016/j.bcmd.2016.12.004. PMID: 28012701
Utz J, Whitley CB, van Giersbergen PL, Kolb SA
Mol Genet Metab 2016 Feb;117(2):172-8. Epub 2015 Dec 2 doi: 10.1016/j.ymgme.2015.12.001. PMID: 26674302
Doneda D, Lopes AL, Teixeira BC, Mittelstadt SD, Moulin CC, Schwartz IV
Clin Nutr 2015 Aug;34(4):727-31. Epub 2014 Aug 30 doi: 10.1016/j.clnu.2014.08.010. PMID: 25239509

Diagnosis

Zhang X, Wu Y, Wang L, Wu Q, Liu Q, Li R
Clin Lab 2023 Apr 1;69(4) doi: 10.7754/Clin.Lab.2022.220816. PMID: 37057944
Di Rocco M, Andria G, Bembi B, Carubbi F, Giona F, Giuffrida G, Linari S, Sibilio M, Spina V, Cappellini MD
Mol Genet Metab 2012 Nov;107(3):521-5. Epub 2012 Aug 17 doi: 10.1016/j.ymgme.2012.08.009. PMID: 22954583
Ali MA, Saleh FM, Das K, Latif T
Mymensingh Med J 2011 Jul;20(3):490-2. PMID: 21804517
Altarescu G, Renbaum P, Eldar-Geva T, Varshower I, Brooks B, Beeri R, Margalioth EJ, Levy-Lahad E, Elstein D, Zimran A
Blood Cells Mol Dis 2011 Jan 15;46(1):15-8. Epub 2010 Jun 1 doi: 10.1016/j.bcmd.2010.04.008. PMID: 20684885
de Fost M, Aerts JM, Hollak CE
Neth J Med 2003 Jan;61(1):3-8. PMID: 12688562

Therapy

Zhang P, Zheng MF, Cui SY, Zhang W, Gao RP
Endocr Metab Immune Disord Drug Targets 2022;22(6):658-662. doi: 10.2174/1871530321666211119145230. PMID: 34802413
Utz J, Whitley CB, van Giersbergen PL, Kolb SA
Mol Genet Metab 2016 Feb;117(2):172-8. Epub 2015 Dec 2 doi: 10.1016/j.ymgme.2015.12.001. PMID: 26674302
Di Rocco M, Andria G, Bembi B, Carubbi F, Giona F, Giuffrida G, Linari S, Sibilio M, Spina V, Cappellini MD
Mol Genet Metab 2012 Nov;107(3):521-5. Epub 2012 Aug 17 doi: 10.1016/j.ymgme.2012.08.009. PMID: 22954583
Parisi MS, Mastaglia SR, Bagur A, Goldstein G, Zeni SN, Oliveri B
Eur J Med Res 2008 Jan 23;13(1):31-8. PMID: 18226995
Barranger JM, Novelli EA
Expert Opin Biol Ther 2001 Sep;1(5):857-67. doi: 10.1517/14712598.1.5.857. PMID: 11728220

Prognosis

Iaccarino Idelson P, Speranza E, Marra M, Pasanisi F, Sammarco R, Galletti F, Strazzullo P, Barbato A
Nutrients 2022 Aug 3;14(15) doi: 10.3390/nu14153180. PMID: 35956356Free PMC Article
Gras-Colomer E, Martínez-Gómez MA, Climente-Martí M, Fernandez-Zarzoso M, Almela-Tejedo M, Giner-Galvañ V, Marcos-Rodríguez JA, Rodríguez-Fernández A, Torralba-Cabeza MÁ, Merino-Sanjuan M
Basic Clin Pharmacol Toxicol 2018 Jul;123(1):65-71. Epub 2018 Mar 30 doi: 10.1111/bcpt.12977. PMID: 29418074
Várkonyi J, Simon Z, Soós K, Poros A
Haematologia (Budap) 2002;32(3):271-5. doi: 10.1163/15685590260461084. PMID: 12611487
Sibille A, Eng CM, Kim SJ, Pastores G, Grabowski GA
Am J Hum Genet 1993 Jun;52(6):1094-101. PMID: 8503443Free PMC Article
Zlotogora J, Sagi M, Zeigler M, Bach G
Am J Med Genet 1989 Apr;32(4):475-7. doi: 10.1002/ajmg.1320320408. PMID: 2773988

Clinical prediction guides

Jandhyala R
BMC Med Res Methodol 2023 May 20;23(1):121. doi: 10.1186/s12874-023-01947-z. PMID: 37210484Free PMC Article
Iaccarino Idelson P, Speranza E, Marra M, Pasanisi F, Sammarco R, Galletti F, Strazzullo P, Barbato A
Nutrients 2022 Aug 3;14(15) doi: 10.3390/nu14153180. PMID: 35956356Free PMC Article
Gras-Colomer E, Martínez-Gómez MA, Climente-Martí M, Fernandez-Zarzoso M, Almela-Tejedo M, Giner-Galvañ V, Marcos-Rodríguez JA, Rodríguez-Fernández A, Torralba-Cabeza MÁ, Merino-Sanjuan M
Basic Clin Pharmacol Toxicol 2018 Jul;123(1):65-71. Epub 2018 Mar 30 doi: 10.1111/bcpt.12977. PMID: 29418074
Buccoliero R, Palmeri S, Ciarleglio G, Collodoro A, De Santi MM, Federico A
J Inherit Metab Dis 2007 Nov;30(6):983. Epub 2007 Nov 12 doi: 10.1007/s10545-007-0597-8. PMID: 17994285
Sibille A, Eng CM, Kim SJ, Pastores G, Grabowski GA
Am J Hum Genet 1993 Jun;52(6):1094-101. PMID: 8503443Free PMC Article

Recent systematic reviews

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Table of contents

    Clinical resources

    Practice guidelines

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

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