Absent biochemical evidence at an early age delayed diagnosis in a patient with a clinically severe form of peroxisomal biogenesis disorder

The aim of the study is determining the level of very long chain fatty acids (VLCFA) is the screening method of choice in suspected peroxisomal disorders. Severe peroxisomal biogenesis defects in particular are usually recognized reliably. We report a patient presenting with typical facial stigmata, a treatment-resistant seizure disorder, and polymicrogyria, whose VLCFA levels were within normal limits until the age of 18 months. Only thereafter an elevation was found. Enzymatic and consecutively molecular-genetic analysis revealed a compound-heterozygous mutation in PEX 6. In conclusion, VLCFA levels within normal limits initially do not rule out global peroxisomal biogenesis defects and should be repeated subsequently. Persisting clinical suspicion justifies further enzymatic and molecular evaluation.