Early visual seizures and progressive myoclonus epilepsy in neuronopathic Gaucher disease due to a rare compound heterozygosity (N188S/S107L)

Epilepsia. 2004 Sep;45(9):1154-7. doi: 10.1111/j.0013-9580.2004.15904.x.

Abstract

Purpose: Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase, is characterized by genotypic and phenotypic heterogeneity. We recently characterized the glucocerebrosidase alleles of a patient with an unusual clinical presentation of type 3 Gaucher disease.

Methods: Initial clinical manifestations appeared at age 11 years as visual seizures.

Results: Subsequent progressive myoclonus and generalized seizures were consistent with an adolescent-onset form of progressive myoclonus epilepsy. However, a specific diagnosis was established only at age 16, because of the absence of hematologic abnormalities and a fairly moderate hepatomegaly. Bone marrow aspirate was slightly positive for Gaucher cells. Demonstration of reduced glucocerebrosidase in the fibroblasts confirmed the diagnosis. The child died at age 19 years. Postmortem sequencing of the glucocerebrosidase gene from cultured fibroblasts demonstrated a rare compound heterozygote for N188S/S107L.

Conclusions: This unusual presentation of Gaucher disease indicates that if clinical and neurophysiological findings in adolescents with initial visual seizures and myoclonus suggest a progressive disorder, enzymatic assay is mandatory, even in the absence of the classic neurologic and systemic signs of the disease. Early differential diagnosis from other forms of progressive myoclonus epilepsy with similar clinical presentation may help provide appropriate genetic counseling.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Epilepsy, Reflex / diagnosis
  • Epilepsy, Reflex / enzymology
  • Epilepsy, Reflex / genetics
  • Evoked Potentials, Somatosensory / genetics
  • Evoked Potentials, Somatosensory / physiology
  • Evoked Potentials, Visual / genetics
  • Evoked Potentials, Visual / physiology
  • Exons
  • Gaucher Disease / diagnosis
  • Gaucher Disease / enzymology
  • Gaucher Disease / genetics*
  • Genetic Counseling
  • Genetic Heterogeneity
  • Genotype
  • Glucosylceramidase / genetics*
  • Humans
  • Male
  • Mutation / genetics*
  • Myoclonic Epilepsies, Progressive / diagnosis
  • Myoclonic Epilepsies, Progressive / enzymology
  • Myoclonic Epilepsies, Progressive / genetics*
  • Phenotype
  • Seizures / diagnosis
  • Seizures / enzymology
  • Seizures / genetics*

Substances

  • Glucosylceramidase