Zellweger Syndrome with Novel PEX1 Variants and Unusual Periventricular Leukomalacia in a Term Infant: A Case Report

Zellweger syndrome is a rare disorder due to mutations in PEX genes, resulting in defective peroxisome biogenesis and multisystemic features. This is a case of a male infant born at term via caesarean section due to breech presentation, who experienced perinatal asphyxia and demonstrated the characteristic features of the syndrome such as facial dysmorphism, hypotonia, renal cysts and hepatic dysfunction along with a novel finding of Periventricular Leukomalacia (PVL). Despite intensive supportive care, the infant’s condition progressively worsened, with complications such as aspiration pneumonia and sepsis leading to death at five months. Genetic testing revealed two previously unreported heterozygous variants in the PEX1 gene: a splice site variant within intron 13 and a frameshift mutation in exon 5, both predicted to significantly impair protein function. The PVL, which is rarely seen in a term infant with Zellweger syndrome, is caused by oxidative stress, mitochondrial dysfunction, and defective myelination. This case highlights the importance of genetic testing for diagnosis as well as genotype-phenotype correlation, thereby adding to the existing mutation database. There is no cure and life expectancy is short, but early diagnosis and supportive care can improve quality of life.