Zellweger syndrome (ZS) comprises of 14 complementation groups; these constitute the most common and most severe phenotypic class of Peroxisome Biogenesis Disorders (PBD). PBD12A is a subtype of ZS that is caused by PEX19 dysfunction. The absence of peroxisomes impairs catabolism and detoxification of various compounds, as well as plasmalogen biosynthesis. Reported clinical features of PBD12A include neonatal hypotonia, poor growth development, CNS and skeletal abnormalities, epilepsy, hydrocephaly, genital abnormalities, and subtle dysmorphic features (including cranial and ear asymmetry, low hairline, triangular face, widely open anterior and posterior fontanelles, and broad nasal bridge). Other anomalies include hyperbilirubenia and elevated liver activity.
Diagnosis of PBD is mainly determined by serum measurement of very long chain fatty acids (VLCFA), plasmalogen, as well as phytanic and pristanic acid levels; deficient oxidation activity leads to abnormally increased VLCFA, phytanic, and pristanic acid levels, and decreased plasmalogen levels. Immunofluorescence of patient cells is used to confirm absence of peroxisomes. Complementation testing of PBD related genes (peroxins) can identify the candidate gene for mutation analysis. Therapy is currently focused on management of the involved symptoms.