The clinical manifestations of 27 patients affected with peroxisomal disorders and seen between 1982 and 1997 are described from the Hopital Necker-Enfants Malades, Paris, and other centers. Zellweger syndrome, neonatal adrenoleukodystrophy, or infantile Refsum disease occurred in 20 cases. One had rhizomelic chondrodysplasia punctata, and 1 had classical Refsum disease. The remaining 5 presented with unusually mild or atypical symptoms, suggesting a peroxisome biogenesis disorder, with variable expression in different tissues. Clinical symptoms vary with age: neonatal- hypotonia, seizures, dysmorphisms, and skeletal abnormalities; 1-6 months- failure to thrive, hepatomegaly, jaudice, retinopathy, cataract; 6 months - 4 years- neurological presentation, retardation, visual and hearing impairment, osteoporosis; beyond 4 years- behavior changes, intellectual deterioration, leukoencephalopathy, peripheral neuropathy. Assay of plasma very long chain fatty acids (VLCFAs) is a general screening test for peroxisomal disorders, but VLCFA elevation may be small in mild variant patients. Diagnostic assays should include plasma phytanic, pristanic, and docosahexaenoic acids; urine organic acids and pipecolic acid; red blood cell plasmalogens; fibroblast plasmalogen synthesis; and liver cytochemical localization of peroxisomal proteins. The diagnostic usefulness of pipecolic acid measured on routine amino acid chromotography is emphasized, especially in atypical cases. [1]

COMMENT. Peroxisomal disorders may present in a variety of clinical manifestations, often age-dependent. The most common peroxisomal disorder, X-adrenoleukodystrophy (X-ALD), may present with hyperactivity and attention disorders. According to an editorial commentary, the diagnosis of X-ALD should be suspected when ADHD is complicated by dementia, incoordination, or auditory or visual impairment [2]. The demonstration of abnormally high levels of VLCFAs in plasma is the prototype initial test. Studies of cultured skin fibroblasts are the most helpful additional test. Other diagnostic assays, including immunochemical assays, are necessary in diagnosis of atypical cases. Diagnosis is important in genetic counseling and disease prevention.