General description

D-bifunctional protein deficiency results from biallelic pathogenic variants in the HSD17B4 gene located on chromosome 5q23.1. The encoded protein serves as a crucial peroxisomal enzyme that catalyzes the second and third steps of peroxisomal fatty acid β-oxidation through its dual enzymatic activities: 2-enoyl-coenzyme A (CoA) hydratase and 3-hydroxyacyl-CoA dehydrogenase functions. This bifunctional enzyme is essential for the oxidation of various peroxisomal substrates, including very long-chain acyl-CoAs, branched-chain acyl-CoAs such as pristanoyl-CoA, and bile acid precursors.

Clinical manifestations

The clinical presentation of DBP deficiency demonstrates remarkable heterogeneity, ranging from severe neonatal-onset disease to milder juvenile forms with extended survival. The classical neonatal presentation is characterized by early-onset hypotonia and seizures within the first month of life. These foundational symptoms are typically accompanied by feeding difficulties, developmental stagnation, and progressive neurological deterioration. Neurological manifestations extend beyond the initial presentation to include progressive visual impairment, sensorineural hearing loss, and severe psychomotor developmental delays.

References

1. Landau, Yuval E., et al. "Four patients with D-bifunctional protein (DBP) deficiency: Expanding the phenotypic spectrum of a highly variable disease." Molecular genetics and metabolism reports 25 (2020): 100631.