Research Information System
MOLECULAR SYNDROMOLOGY, vol.17, no.1, pp.74-81, 2026 (SCI-Expanded, Scopus)
Introduction: Bi-allelic variants in the 17-hydroxysteroid dehydrogenase type 4 gene (HSD17B4) cause the extremely rare autosomal recessive disorder known as peroxisomal D-bifunctional protein deficiency (D-BPD) (#OMIM 261515). This protein mediates hydration and dehydrogenation in the peroxisomal fatty acid beta-oxidation pathway. Because of this, very long-chain fatty acids (VLCFAs), branched fatty acids (pristanic acid), and bile acid components cannot be broken down without it. Clinically, it causes developmental delay with neonatal hypotonia, seizures, and dysmorphic features. The D-BPD is divided into four subtypes according to the region affected by the variant causing the disorder. Case Presentation: Two newborns presented with severe hypotonia, intractable seizures, and dysmorphic facial features (microretrognathia, hypertelorism). These cases showed high levels of VLCFAs and were diagnosed by next-generation gene sequencing tests. We found a known homozygous variant (c.46G>A/p.Gly16Ser) in the HSD17B4 gene of case 1, which had been linked to D-BPD type III before. Case 1 developed adrenal insufficiency during follow-up. In case 2, we discovered a novel homozygous variant (c. 559A>T, p. Ile187Phe) in the HSD17B4 gene in exon 8 that led to the development of D-BPD type III. The American College of Medical Genetics and Genomics (ACMG) classifies this missense variant as likely pathogenic. Discussion: The D-BPD type III cases profiled in this report exhibit a severe phenotype, which includes dysmorphic facial features, severe hypotonia, and refractory seizures that manifest from birth. One month after the VLCFAs analysis revealed something suggestive of a peroxisomal disorder, a targeted gene panel analysis could confirm the diagnosis.