Zellweger syndrome and secondary mitochondrial myopathy.

Abstract

Defects in peroxisomes such as those associated with Zellweger syndrome (ZS) can influence diverse intracellular metabolic pathways, including mitochondrial functioning. We report on an 8-month-old female infant and a 6-month-old female infant with typical clinical, radiological and laboratory features of Zellweger syndrome; light microscopic and ultrastructural evidence of mitochondrial pathology in their muscle biopsies; and homozygous pathogenic mutations of the PEX16 gene (c.460 + 5G > A) and the PEX 12 gene (c.888_889 del p.Leu297Thrfs*12), respectively. Additionally, mitochondrial respiratory chain enzymology analysis in the first girl showed a mildly low activity in complexes II–III and IV. We also review five children previously reported in the literature with a presumptive diagnosis of ZS and additional mitochondrial findings in their muscle biopsies. In conclusion, this is the first study of patients with a molecularly confirmed peroxisomal disorder with features of a concomitant mitochondrial myopathy and underscores the role of secondary mitochondrial dysfunction in Zellweger syndrome, potentially contributing to the clinical phenotype.