Mitochondria and Peroxisome Crosstalk in Peroxisome Biogenesis Disorder <scp>8A</scp> Caused by a Rare Variant in <scp><i>PEX16</i></scp> Gene

Peroxisome biogenesis disorder 8A is a rare autosomal recessive disorder caused by mutations in the PEX16 gene. We report the clinical, biochemical, and molecular features of a patient harboring the homozygous NM_004813.4: c.526C>T, p.(Arg176*) mutation in PEX16 associated with mitochondrial dysfunction. This newborn presented with microcephaly, encephalopathy, hypotonia, failure to thrive, hepatomegaly, and abnormal retinal pigmentation. He had elevated plasma very long-chain fatty acids. Skeletal muscle biopsy revealed significant mitochondrial depletion with deficiencies of the respiratory chain Complexes I-IV, with significant reductions in cytochrome c oxidase and citrate synthase activity. The peroxisome biogenesis disorder 8A was confirmed by whole genome sequencing. This is the first case delineating the association of mitochondrial dysfunction with peroxisome biogenesis disorder 8A caused by the above mutation. Further studies are needed to elucidate the underlying pathophysiological mechanisms of mitochondria and peroxisome crosstalk.