title: D-bifunctional protein deficiency associated with drug resistant infantile spasms.
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.
authors.affiliation: Department of Pediatrics, Section of Pediatric Neurology, Policlinico Le Scotte, University of Siena, Siena, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Buoni
authors.forename: Raffaella
authors.initials: R
authors.lastname: Zannolli
authors.forename: Hans
authors.initials: H
authors.lastname: Waterham
authors.forename: Ronald
authors.initials: R
authors.lastname: Wanders
authors.forename: Alberto
authors.initials: A
authors.lastname: Fois
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics*; D000927:Anticonvulsants / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004351:Drug Resistance / Q000235:genetics*; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D017809:Fatal Outcome; D017353:Gene Deletion; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006836:Hydro-Lyases / Q000172:deficiency* / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics; D064029:Peroxisomal Multifunctional Protein-2; D012131:Respiratory Insufficiency / Q000209:etiology / Q000401:mortality; D013036:Spasms, Infantile / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D020888:Vigabatrin / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D005819:Genetic Markers; D015067:17-Hydroxysteroid Dehydrogenases; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D020888:Vigabatrin