Selective neuronal lipidosis and neuroaxonal dystrophy of the dorsal nucleus of Clarke and lateral cuneate nucleus were the neuropathological findings in 3 males with Zellweger syndrome examined at the Medical Unit S Carolina, Charleston, SC, the John F. Kennedy Institute, Johns Hopkins Univ, Baltimore, MD, and the Philadelphia Children’s Hosp. Large amounts of abnormal cholesterol esters containing saturated and monosaturated very long-chain fatty acids were demonstrated in the striated neurons of the dorsal thoracic cord. The CNS neurons of these patients manifested the same morphological alteration as adrenocortical cells of adreno-leukodystrophy, and many of the striated neurons were degenerate or necrotic. It is suggested that a more generalized defect in neuronal fatty acid metabolism may explain the neuronal migration defects characteristic of Zellweger syndrome. These consist of pachygyria, micropolygyria and cerebral and cerebellar heterotopia. [1]

COMMENT. CHR (Zellweger) syndrome, transmitted as an autosomal recessive, is invariably fatal within a few months after birth. Prenatal diagnosis may be made by amniocentesis and the production of very-long-chain fatty acids (VLCFA) from cultured amniocytes [2, 3].The determination of VLCFA in the blood permits prompt diagnostic confirmation of CHRS in the infant with dysmorphic facial and skull features, liver enlargement and fibrosis, renal cysts, stippled calcifications of the patellae, Brushfield’s spots, optic atrophy and retinal pigmentation. Zellweger syndrome is a peroxisomal disorder. The lacking peroxisomes are cytoplasmic organelles containing oxidases and catalase and are involved in metabolism of hydrogen peroxide, fatty acids and bile acids.