Peroxisomal disorders — branching viva

Branch 1 — The dysmorphic neonate

The unifying diagnosis is a peroxisome biogenesis disorder in the Zellweger spectrum. The combination of dysmorphism (high forehead, large fontanelle, broad nasal bridge), profound hypotonia, seizures, hepatomegaly with cholestasis, and chondrodysplasia punctata is characteristic, and the severity points to the Zellweger syndrome end of the continuum. The mechanistic group is the biogenesis disorders, caused by recessive PEX gene defects that prevent functional peroxisomes from forming. ^{[1] [2]}

The confirmatory investigation is the plasma very-long-chain fatty acid panel, which is abnormal across the whole Zellweger spectrum. The biochemical signature is global: elevated very-long-chain fatty acids, elevated phytanic and pristanic acid, elevated bile-acid intermediates, and deficient red-cell plasmalogens. Molecular testing of the PEX gene panel confirms the diagnosis and enables family testing and prenatal diagnosis. ^{[1] [2]}

The disease-directed therapy is cholic acid, which replaces the missing bile-acid end-product and reduces the toxic intermediates. Beyond cholic acid the management is supportive and multidisciplinary: fat-soluble vitamins, seizure control, feeding and growth support, hearing and vision rehabilitation. The prognosis for the severe end is guarded, and early goals-of-care discussion with the family is essential. ^[2]