Document Detail

Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup.
MedLine Citation:
PMID:  12595585     Owner:  NLM     Status:  MEDLINE    
Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, presents with a wide spectrum of manifestations. Although Gaucher disease has been divided into three clinical types, patients with atypical presentations continue to be recognized. A careful phenotypic and genotypic assessment of patients with unusual symptoms may help define factors that modify phenotype in this disorder. One such example is a rare subgroup of patients with type 3 Gaucher disease who develop progressive myoclonic epilepsy. We evaluated 16 patients with myoclonic epilepsy, nine of whom were diagnosed by age 4 y with severe visceral involvement and myoclonus, and seven with a more chronic course, who were studied between ages 22 and 40. All of the patients had abnormal horizontal saccadic eye movements. Fourteen different genotypes were encountered, yet there were several shared alleles, including V394L (seen on two alleles), G377S (seen on three alleles), and L444P, N188S, and recombinant alleles (each found on four alleles). V394L, G377S, and N188S are mutations that have previously been associated with non-neuronopathic Gaucher disease. The spectrum of genotypes differed significantly from other patients with type 3 Gaucher disease, where genotypes L444P/L444P and R463C/null allele predominated. Northern blot studies revealed a normal glucocerebrosidase transcript, whereas Western studies showed that the patients studied lacked the processed 56 kD isoform of the enzyme, consistent with neuronopathic Gaucher disease. Brain autopsy samples from two patients demonstrated elevated levels of glucosylsphingosine, a toxic glycolipid, which could contribute to the development of myoclonus. Thus, although there were certain shared mutant alleles found in these patients, both the lack of a shared genotype and the variability in clinical presentations suggest that other modifiers must contribute to this rare phenotype.
Joseph K Park; Eduard Orvisky; Nahid Tayebi; Christine Kaneski; Mary E Lamarca; Barbara K Stubblefield; Brian M Martin; Raphael Schiffmann; Ellen Sidransky
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pediatric research     Volume:  53     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-02-21     Completed Date:  2003-08-27     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  387-95     Citation Subset:  IM    
Clinical Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
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MeSH Terms
Brain / metabolism
Child, Preschool
DNA Mutational Analysis
Epilepsies, Myoclonic / genetics*,  metabolism
Gaucher Disease / genetics*,  metabolism
Glucosylceramidase / genetics*,  metabolism
Psychosine / analogs & derivatives
Sphingosine / analogs & derivatives*,  metabolism
Transcription, Genetic
Reg. No./Substance:
123-78-4/Sphingosine; 2238-90-6/Psychosine; 52050-17-6/sphingosyl beta-glucoside; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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