Type 2 Gaucher Disease: An Expanding Phenotype

Tayebi, Nahid; Stone, Deborah L.; Sidransky, Ellen

doi:10.1006/mgme.1999.2918

Cited by 43 publications

(35 citation statements)

References 70 publications

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“…Patients with Type 2 GD invariably exhibit clinical signs in the first year of life, although the type and severity of manifestations can vary widely [5,6]. While newborns often appear normal at birth and develop neurological signs with a rapid decline in health within the first year [6], others present prenatally or as neonates.…”

Section: Phenotypes Associated With Type 2 Gdmentioning

confidence: 99%

The clinical management of type 2 Gaucher disease

Weiss

Gonzalez

Lopez

et al. 2015

Molecular Genetics and Metabolism

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Gaucher disease, the inherited deficiency of the enzyme glucocerebrosidase, is the most common of the lysosomal storage disorders. Type 2 Gaucher disease, the most severe and progressive form, manifests either prenatally or in the first months of life, followed by death within the first years of life. The rarity of the many lysosomal storage disorders makes their diagnosis a challenge, especially in the newborn period when the focus is often on more prevalent illnesses. Thus, a heightened awareness of the presentation of these rare diseases is necessary to ensure their timely consideration. This review, designed to serve as a guide to physicians treating newborns and infants with Gaucher disease, discusses the presenting manifestations of Type 2 Gaucher disease, the diagnostic work-up, associated genotypes and suggestions for management. We also address the ethical concerns that may arise with this progressive and lethal disorder, since currently available treatments may prolong life, but do not impact the neurological manifestations of the disease.

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Section: Phenotypes Associated With Type 2 Gdmentioning

confidence: 99%

The clinical management of type 2 Gaucher disease

Weiss

Gonzalez

Lopez

et al. 2015

Molecular Genetics and Metabolism

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“…Ultrastructural electron microscopy of epidermal samples may have promise in the discrimination between type 2 GD and type 1 or type 3 [5; 96]. Skin samples from patients with type 2 GD show abnormal arrays of loosely packed lamellar body-derived sheets in the stratum corneum, as opposed to the normal lamellar bilayer structures found in the stratum corneum of control subjects and patients with types 1 and 3 GD [5].…”

Section: Diagnosismentioning

confidence: 99%

“…Type 2 GD makes up the minority of GD cases overall. In general, GD has an estimated frequency of 1 in 100,000 to 500,000 live births [4; 5]. Like other types of GD, type 2 GD is pan-ethnic in occurrence.…”

Section: Introductionmentioning

confidence: 99%

Type 2 Gaucher disease: Phenotypic variation and genotypic heterogeneity

Gupta

Oppenheim

Kauvar

et al. 2011

Blood Cells, Molecules, and Diseases

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Gaucher disease (GD), the most common lysosomal storage disease, results from a deficiency of the lysosomal enzyme glucocerebrosidase. GD has been classified into 3 types, of which type 2 (the acute neuronopathic form) is most severe, presenting pre-or perinatally, or in the first few months of life. Traditionally, type 2 GD was considered to have the most uniform clinical phenotype when compared to other GD subtypes. However, case studies over time have demonstrated that type 2 GD, like types 1 and 3, manifests with a spectrum of phenotypes. This review includes case reports that illustrate the broad range of clinical presentations encountered in type 2 GD, as well as a discussion of associated manifestations, pathological findings, diagnostic techniques, and a review of current therapies. While type 2 GD is generally associated with severe mutations in the glucocerebrosidase gene, there is also significant genotypic heterogeneity observed.

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“…] (L444P) [Beutler and Gelbart, 1998] and is present in the sequence of the glucocerebrosidase pseudogene located 16 kb downstream of the human glucocerebrosidase gene 8 [Horowitz et al, 1989]. About another 50 different mutations have been detected in association with type 2 disease Tayebi et al, 1998Tayebi et al, , 1999Choy et al, 2000;Stone et al, 2000a]. A recent study on a cohort of 31 patients demonstrated the significant phenotypic and genotypic heterogeneity among patients with type 2 Gaucher disease [Stone et al, 2000a].…”

Section: Discussionmentioning

confidence: 96%

Intrauterine onset of acute neuropathic type 2 Gaucher disease: Identification of a novel insertion sequence

Felderhoff‐Mueser

Uhl

Penzel

et al. 2004

American J of Med Genetics Pt A

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A subset of patients with type 2 Gaucher disease is characterized by intrauterine onset of rapidly progressive neuropathic disease, arthrogryposis, hydrops fetalis and in some cases restrictive dermopathy. beta-Glucocerebrosidase (beta-glucosidase) activity is usually low or undetectable. In most cases death ensues either in-utero or within hours or days after birth. We report on an infant born to non-consanguineous parents of Caucasian origin presenting at birth with hydrops, arthrogryposis, severe respiratory distress, hepatosplenomegaly, and liver failure. Death occurred within several hours after delivery and autopsy revealed typical Gaucher cells in multiple organs in combination with severe apoptotic neurodegeneration throughout the brain. beta-Glucocerebrosidase activity was 1% of the norm in fibroblasts and a novel heterozygous insertion c.1515_1516insAGTGAGGGCAAT was identified by genomic sequencing and an insertion-specific seminested PCR. In addition, molecular studies revealed a previously described in type 1 Gaucher disease missense mutation c.476G --> A which results in a heterozygous substitution of R120Q. Our observations confirm considerable genotypic heterogeneity in patients with type 2 Gaucher disease. The transheterozygous combination of a mutation, previously described in type 1 Gaucher disease, together with a newly identified insertion may result in this severe phenotype.

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Type 2 Gaucher Disease: An Expanding Phenotype

Cited by 43 publications

References 70 publications

The clinical management of type 2 Gaucher disease

The clinical management of type 2 Gaucher disease

Type 2 Gaucher disease: Phenotypic variation and genotypic heterogeneity

Intrauterine onset of acute neuropathic type 2 Gaucher disease: Identification of a novel insertion sequence

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