D-bifunctional protein deficiency and Zellweger spectrum disorders: clinical-genetic parallels and differential diagnosis

Zellweger syndrome (ICD-10: Q87.8; OMIM: #214100) is a multisystemic peroxisomal disorder caused by an autosomal recessive mutation in genes of the PEX family. Distinctive features of the condition include facial dysmorphism and neurological disorders, manifesting as convulsions, hypotonia, epileptic seizures and leukodystrophy. A similar set of symptoms is seen in another disorder within the spectrum of peroxisomal biogenesis disorders, caused by an autosomal recessive mutation in the HSD17B4 gene and designated in the international nomenclature of diseases as D-bifunctional protein deficiency (ICD-10: E88.8; OMIM: #261515). Despite differences in their molecular-genetic basis, the aforementioned diseases share significant phenotypic similarities, which considerably complicates their clinical differentiation and necessitates molecular-genetic testing to verify the diagnosis. The aim of this study is to review the current literature on Zellweger syndrome and D-bifunctional protein deficiency, and to analyse their clinical similarities, the characteristics of their differential diagnosis, and current treatment approaches. Materials and methods: An analysis was conducted of domestic and international scientific literature on Zellweger syndrome and D-bifunctional protein deficiency, using the electronic databases PubMed, NIH, Google Scholar, ResearchGate and the eLibrary.ru scientific library; data on clinical manifestations, molecular-genetic characteristics, diagnostic criteria and therapeutic strategies, including modern approaches to targeted therapy, were selected and systematised.

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