Cardiovascular fibrosis, hydrocephalus, ophthalmoplegia, and visceral involvement in an American child with Gaucher disease

Stone, Deborah L.

doi:10.1136/jmg.37.11.e40

Cited by 10 publications

(6 citation statements)

References 12 publications

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“…Categorization into three main subtypes is based on clinical criteria rather than the molecular genotype. Additional variants have emerged adding hydrocephalus, valvular heart disease, cardiovascular fibrosis or calcification, oculomotor apraxia, corneal opacities, deformed toes, and fibrous thickening of spleen and liver capsules to the list of possible presentations of neuronopathic Gaucher disease [Abrahamov et al, 1995; Chabas et al, 1995; Uyama et al, 1997; Bohlega et al, 2000; Stone et al, 2000; Inui et al, 2001]. We add another clinical variant to this list.…”

Section: Discussionmentioning

confidence: 99%

“…Children with variant neuronopathic Gaucher disease and a spectrum of abnormalities including valvular heart disease, cardiovascular calcifications and/or fibrosis, oculomotor apraxia, hydrocephalus, fibrous thickening of liver and spleen have been previously reported [Abrahamov et al, 1995; Chabas et al, 1995; Uyama et al, 1997; Bohlega et al, 2000; Stone et al, 2000; Inui et al, 2001]. Many of these children were subsequently found to be homozygous for the mutation D409H in the β‐glucosidase gene and classified as Gaucher disease type IIIC or Gaucher‐like disease (McKusick 231005) [Abrahamov et al, 1995; Chabas et al, 1995; Uyama et al, 1997; Bohlega et al, 2000].…”

Section: Introductionmentioning

confidence: 99%

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Variant Gaucher disease characterized by dysmorphic features, absence of cardiovascular involvement, laryngospasm, and compound heterozygosity for a novel mutation (D409H/C16S)

et al. 2002

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A 20-month-old girl with developmental delay, dysmorphic features, horizontal supranuclear gaze palsy, retrocollis, and episodes of laryngospasm was diagnosed with variant neuronopathic Gaucher disease. The diagnosis was made enzymatically. Mutation analysis showed compound heterozygosity for D409H and a previously unreported mutation C16S. The presence of dysmorphic features, laryngospasm, absent cardiac findings, and the severe clinical phenotype distinguishes our case from other cases of variant neuronopathic Gaucher disease. We therefore propose to extend the spectrum of variant Gaucher disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Variant Gaucher disease characterized by dysmorphic features, absence of cardiovascular involvement, laryngospasm, and compound heterozygosity for a novel mutation (D409H/C16S)

et al. 2002

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“…The enhanced expression of cysteine proteinases in GCs and other cells might contribute to lytic bone lesions (Moran et al 2000). The effect of the paralysosomal GlcCer load is worth exploring in the repeatedly reported atypical complex and atypical phenotypes of GD (Bodamer et al 2002;George et al 2001;Inui et al 2001;Stone et al 2000;Uyama et al 1992;Wilson et al 1985) and even in the evolution of Parkinson syndrome in GD (Tayebi et al 2003;Wong K et al 2004). Further manifestations of the expanding phenotypic spectrum are mentioned in a recent survey (Sidransky 2004).…”

Section: Glucosylceramide Transfermentioning

confidence: 99%

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

Elleder

2006

J of Inher Metab Disea

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SummaryGaucher disease (GD), deficiency of acid glucosylceramidase (GlcCer‐ase) is characterized by deficient degradation of beta‐glucosylceramide (GlcCer). It is well known that, in GD, the lysosomal accumulation of uncleaved GlcCer is limited to macrophages, which are gradually converted to storage cells with well known cytology—Gaucher cells (GCs). On the basis of previous studies of the disorder and of a comparison with other lysosomal enzymopathies affecting degradation of the GlcCer‐based glycosphingolipid series, it is hypothesized that in other cell types (i.e. non‐macrophage cells) the uncleaved GlcCer, in GlcCer‐ase deficiency, is transferred to other cell compartments, where it may be processed and even accumulated to various degrees. The consequence of the abnormal extralysosomal load may differ according to the cell type and compartment targeted and may be influenced by genetically determined factors, by a number of acquired conditions, including the current metabolic situation. The sequelae of the uncleaved GlcCer extralysosomal transfer may range from probably innocent or positive stimulatory, to the much more serious, in which it interferes with a variety of cell functions, and in extreme cases, can lead to cell death. This alternative processing of uncleaved GlcCer may help to explain tissue alterations seen in GD that have, so far, resisted explanation based simply on the presence of GCs. Paralysosomal alternative processing may thus go a long way towards filling a long‐standing gap in the understanding of the molecular pathology of the disorder. The impact of this alternative process will most likely be inversely proportional to the level of residual GlcCer‐ase activity. Lysosomal sequestration of GlcCer in these cells is either absent or in those exceptional cases where it does occur, it is exceptional and rudimentary. It is suggested that paralysosomal alternative processing of uncleaved GlcCer is the main target for enzyme replacement therapy. The mechanism responsible for GlcCer transfer remains to be elucidated. It may also help in explaining the so far unclear origin of glucosylsphingosine (GlcSph) and define the mutual relation between these two processes.

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“…An increasing number of subgroups of patients with Gaucher disease and unique phenotypes have been reported recently. Included among these are patients with parkinsonian symptoms (10,11), pulmonary hypertension (12), cardiac calcifications and/or fibrosis (13)(14)(15), and hydrops fetalis or the collodion baby phenotype (16,17). Unique phenotypes are especially prevalent among patients classified as having type 3 Gaucher disease.…”

mentioning

confidence: 99%

Myoclonic Epilepsy in Gaucher Disease: Genotype-Phenotype Insights from a Rare Patient Subgroup

et al. 2003

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Cardiovascular fibrosis, hydrocephalus, ophthalmoplegia, and visceral involvement in an American child with Gaucher disease

Cited by 10 publications

References 12 publications

Variant Gaucher disease characterized by dysmorphic features, absence of cardiovascular involvement, laryngospasm, and compound heterozygosity for a novel mutation (D409H/C16S)

Variant Gaucher disease characterized by dysmorphic features, absence of cardiovascular involvement, laryngospasm, and compound heterozygosity for a novel mutation (D409H/C16S)

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

Myoclonic Epilepsy in Gaucher Disease: Genotype-Phenotype Insights from a Rare Patient Subgroup

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