Case studyAbsence of biochemical evidence at an early age delays diagnosis in a patient with a clinically severe peroxisomal biogenesis disorder

•Normal VLCFA at an early age do not rule out peroxisomal biogenesis disorder.•VLCFA profiles under ketogenic diet and peroxisomal disorder differ significantly.•Diagnostic reevaluation is necessary when clinical suspicion persists.•Enzyme analysis, complementation group and genetic testing are diagnostic in PBD.

Analysis of the plasma levels of very long chain fatty acids (VLCFA) is a primary screening method for peroxisomal disorders and usually identifies severe peroxisomal biogenesis defects reliably. We report a patient presenting with typical facial stigmata, a treatment resistant seizure disorder and polymicrogyria, whose plasma VLCFA levels were within normal limits until the age of 18 months. Only thereafter an elevation was found. Subsequent enzymatic and molecular genetic analysis revealed compound heterozygous mutations in the PEX6 gene. In conclusion, normal VLCFA levels do not necessarily exclude global peroxisomal biogenesis defects and the analysis should be repeated subsequently. Persisting clinical suspicion justifies further enzymatic and molecular evaluation.