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Gaucher disease type II(GD2)

MedGen UID:
78652
Concept ID:
C0268250
Disease or Syndrome
Synonyms: Acute neuronopathic Gaucher's disease; Gaucher disease type 2; Gaucher Disease Type 2 (Acute); Gaucher disease, acute neuronopathic type; Gaucher disease, infantile cerebral; GD 2; GD II; GD2
SNOMED CT: Glucocerebrosidase deficiency type II (12246008); Acute neuronopathic Gaucher disease (12246008); Infantile Gaucher disease (12246008); Cerebral acute Gaucher disease (12246008); Acute neuronopathic Gaucher's disease (12246008); Infantile Gaucher's disease (12246008); Gaucher's disease, type II (12246008); Acute cerebral Gaucher's disease (12246008); Glucosylceramidase deficiency, acute type (12246008); Infantile cerebral Gaucher's disease (12246008)
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:0009266
OMIM®: 230900
Orphanet: ORPHA77260

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
Type II Gaucher disease (GD2) is an acute neuronopathic form of the disorder with onset in infancy and death often by 2 years of age. Patients are usually normal at birth, but develop hepatosplenomegaly, developmental regression, and growth arrest within a few months of age. Neurologic deterioration proceeds rapidly, with cranial nerve and extrapyramidal tract involvement (Stone et al., 2000).  http://www.omim.org/entry/230900
From MedlinePlus Genetics
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).

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.

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.

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.

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

Clinical features

From HPO
Double aortic arch
MedGen UID:
488819
Concept ID:
C0265883
Congenital Abnormality
A conenital abnormality of the aortic arch in which the two embryonic aortc arches form a vascular ring that surrounds the trachea or esophagus and then join to form the descending aorta. Double aortic arch can cause symptoms because of compression of the esophagus (dysphagia, cyanosis while eating) or trachea (stridor).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Protuberant abdomen
MedGen UID:
340750
Concept ID:
C1854928
Finding
A thrusting or bulging out of the abdomen.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
Bulbar signs
MedGen UID:
347246
Concept ID:
C1856507
Finding
Oculomotor apraxia
MedGen UID:
483686
Concept ID:
C3489733
Disease or Syndrome
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancelation of the vestibulo-ocular reflex.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Trismus
MedGen UID:
21671
Concept ID:
C0041105
Disease or Syndrome
Limitation in the ability to open the mouth.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Bronchiolitis
MedGen UID:
14235
Concept ID:
C0006271
Disease or Syndrome
Inflammation of the bronchioles.
Cough
MedGen UID:
41325
Concept ID:
C0010200
Sign or Symptom
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.
Stridor
MedGen UID:
11613
Concept ID:
C0038450
Sign or Symptom
Stridor is a high pitched sound resulting from turbulent air flow in the upper airway.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Recurrent aspiration pneumonia
MedGen UID:
152887
Concept ID:
C0747651
Disease or Syndrome
Increased susceptibility to aspiration pneumonia, defined as pneumonia due to breathing in foreign material, as manifested by a medical history of repeated episodes of aspiration pneumonia.
Esotropia
MedGen UID:
4550
Concept ID:
C0014877
Disease or Syndrome
A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more.
Ophthalmoplegia
MedGen UID:
45205
Concept ID:
C0029089
Sign or Symptom
Paralysis of one or more extraocular muscles that are responsible for eye movements.
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.

Professional guidelines

PubMed

Chien YH, Lee NC, Chen PW, Yeh HY, Gelb MH, Chiu PC, Chu SY, Lee CH, Lee AR, Hwu WL
Orphanet J Rare Dis 2020 Feb 3;15(1):38. doi: 10.1186/s13023-020-1322-z. PMID: 32014045Free PMC Article
Anderson S
J Pediatr Health Care 2018 May-Jun;32(3):285-294. doi: 10.1016/j.pedhc.2017.04.016. PMID: 29678259
Matern D, Gavrilov D, Oglesbee D, Raymond K, Rinaldo P, Tortorelli S
Semin Perinatol 2015 Apr;39(3):206-16. Epub 2015 Apr 16 doi: 10.1053/j.semperi.2015.03.005. PMID: 25891428

Curated

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

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

Recent clinical studies

Diagnosis

Koto Y, Sakai N, Lee Y, Kakee N, Matsuda J, Tsuboi K, Shimozawa N, Okuyama T, Nakamura K, Narita A, Kobayashi H, Uehara R, Nakamura Y, Kato K, Eto Y
Mol Genet Metab 2021 Jul;133(3):277-288. Epub 2021 May 12 doi: 10.1016/j.ymgme.2021.05.004. PMID: 34090759
Basgalupp SP, Donis KC, Siebert M, E Vairo FP, Artigalas O, de Camargo Pinto LL, Behringer S, Spiekerkoetter U, Hannibal L, Schwartz IVD
Am J Med Genet A 2021 Aug;185(8):2471-2476. Epub 2021 May 24 doi: 10.1002/ajmg.a.62252. PMID: 34031990
Sharpe LR, Ancliff P, Amrolia P, Gilmour KC, Vellodi A
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S107-10. Epub 2009 Mar 11 doi: 10.1007/s10545-009-1091-2. PMID: 19267217
Garbutt S, Harris CM
Br J Ophthalmol 2000 May;84(5):451-5. doi: 10.1136/bjo.84.5.451. PMID: 10781506Free PMC Article
Tsai FJ, Chen HW, Peng CT, Tsai CH, Hwu WL, Wang TR, Liu SC
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1995 Sep-Oct;36(5):346-50. PMID: 8607360

Prognosis

Basgalupp SP, Donis KC, Siebert M, E Vairo FP, Artigalas O, de Camargo Pinto LL, Behringer S, Spiekerkoetter U, Hannibal L, Schwartz IVD
Am J Med Genet A 2021 Aug;185(8):2471-2476. Epub 2021 May 24 doi: 10.1002/ajmg.a.62252. PMID: 34031990
Sharpe LR, Ancliff P, Amrolia P, Gilmour KC, Vellodi A
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S107-10. Epub 2009 Mar 11 doi: 10.1007/s10545-009-1091-2. PMID: 19267217

Clinical prediction guides

Gornati R, Berra B, Montorfano G, Martini C, Ciana G, Ferrari P, Romano M, Bembi B
J Inherit Metab Dis 2002 Feb;25(1):47-55. doi: 10.1023/a:1015137917508. PMID: 11999980
Garbutt S, Harris CM
Br J Ophthalmol 2000 May;84(5):451-5. doi: 10.1136/bjo.84.5.451. PMID: 10781506Free PMC Article

Supplemental Content

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 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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