D-bifunctional protein deficiency associated with drug resistant infantile spasms

Brain Dev. 2007 Jan;29(1):51-4. doi: 10.1016/j.braindev.2006.06.004. Epub 2006 Aug 21.

Abstract

Peroxisomal disorders appear with a frequency of about 1:5000 in newborns. Peroxisomal D-bifunctional protein (D-BP), encoded by the HSD17B4 gene (gene ID: 3294; locus tag: HGNC:5213, chromosome 5q2; official symbol: HSD17B4; name: hydroxysteroid (17-beta) dehydrogenase; gene type: protein coding) (OMIM *601860), comprises an 80 kDa multifunctional enzyme involved in peroxisomal beta-oxidation of certain fatty acids and the synthesis of bile acids. Its deficiency causes a very severe, Zellweger-like clinical phenotype and most patients die within the first year of life. In this paper, we report a case of D-BP deficiency in a patient with two heterozygous trinucleotide deletions (233_235 del AAG and 824_826 del AGA) in the HSD17B4 gene. The patient suffered from a peculiar epileptic phenotype (i.e. a West syndrome with a "modified hypsarrhythmic pattern"--Hrachovy et al. Epilepsia 1984;25:317-25), clinically appearing as drug-resistant asymmetric spasms. Vigabatrin seemed the most effective among the antiepileptic drugs. The patient died at the age of 23 months owing to respiratory complications. To date, only a few patients with D-BP deficiency have been described in the literature. This case adds to our knowledge of the clinical presentation of bifunctional protein deficiency.

Publication types

  • Case Reports

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / deficiency*
  • 17-Hydroxysteroid Dehydrogenases / genetics*
  • Anticonvulsants / therapeutic use
  • DNA Mutational Analysis
  • Disease Progression
  • Drug Resistance / genetics*
  • Electroencephalography
  • Epilepsy / drug therapy
  • Epilepsy / enzymology
  • Epilepsy / genetics
  • Fatal Outcome
  • Gene Deletion
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Hydro-Lyases / deficiency*
  • Hydro-Lyases / genetics*
  • Infant
  • Male
  • Mutation / genetics
  • Peroxisomal Multifunctional Protein-2
  • Respiratory Insufficiency / etiology
  • Respiratory Insufficiency / mortality
  • Spasms, Infantile / drug therapy
  • Spasms, Infantile / enzymology*
  • Spasms, Infantile / genetics*
  • Vigabatrin / therapeutic use

Substances

  • Anticonvulsants
  • Genetic Markers
  • 17-Hydroxysteroid Dehydrogenases
  • Hydro-Lyases
  • Peroxisomal Multifunctional Protein-2
  • HSD17B4 protein, human
  • Vigabatrin