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An eleven month-old boy presented clinically with craniofacial dysmorphia, severe psychomotor retardation, neurological deterioration, no response to visual and acoustic stimuli, failure to thrive, hepatomegaly and adrenal insufficiency. Specific biochemical markers for a peroxisomal deficiency disorder (Zellweger's syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease) revealed pathological results for very long chain fatty acids, phytanic acid, pristanic acid, plasmalogen biosynthesis and catalase, thus confirming the clinical diagnosis. Comparison of clinical and biochemical findings in the patient with the characteristics of the three peroxisomal deficiency disorders showed overlapping with each of these disorders, which corresponds to the current view that these three peroxisomal disorders differ only with respect to onset and severity of the clinical manifestations, but not with regard to the biochemical defects.

Peroxisomal disorders are genetic metabolic diseases with generalized, multiple, or single functional disturbances of the peroxisome. According to the extent of the functional disturbances 3 groups of diseases can be differentiated: disorders with generalized loss of peroxisomal functions (Zellweger syndrome, ZS; neonatal adrenoleukodystrophy, NALD; infantile Refsum's disease), disorders with multiple enzymatic defects (e.g. rhizomelic chondrodysplasia punctata), and disorders with a single enzymatic defect in the peroxisome, the most important being adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN). Adult Refsum's disease, a genetic neurological disorder with phytanic acid accumulation, is due to a mitochondrial enzyme deficiency, but is often considered together with peroxisomal diseases because of phytanic acid (PHYT) accumulation in most peroxisomal diseases. The main clinical and pathological criteria of the major disorders and the biochemical parameters of their differentiation are presented. Elevated levels of very long chain fatty acids (VLCFA) and/or PHYT are the primary diagnostic markers for all peroxisomal disorders and adult Refsum's disease, respectively. Our investigations disclosed 30 ALD/AMN hemizygotes, 16 ALD/AMN heterozygotes, 8 cases of ZS/NALD and 7 patients with adult Refsum's disease. In addition, 15 cases of peroxisomal disorders were confirmed by biochemical investigations in autopsy material. With regard to peroxisomal disorders, therapeutic concepts exist only for ALD/AMN: corticosteroid substitution for adrenal insufficiency, dietary treatment, and bone marrow transplantation (BMT). Adult Refsum's disease can be treated successfully by dietary therapy. In case of dietary treatment and BMT, assay of VLCFA and/or PHYT is important for the biochemical evaluation of these therapies.

The relative proportions of the diphytanyl, monophytanyl and nonphytanyl triglycerides ("triglyceride pattern"), the phytanic acid content of the triglycerides and the phytanic acid levels in the serum of 3 patients with Refsum's disease (heredopathia atactica polyneuritiformis, phytanic acid storage disease) were estimated by thin-layer chromatography, densitometry and gas chromatography, respectively. The individual triglyceride patterns were clearly dependent on the phytanic acid content of the triglycerides: the more phytanic acid in the triglycerides, the higher the percentage of the diphytanyl and the lower the percentage of the nonphytanyl triglycerides. The monophytanyl triglycerides were also related to the phytanic acid content of the triglycerides, although in a complex manner. The triglyceride pattern can be taken as a parameter of the phytanic acid accumulation in Refsum's disease to be at least as sensitive as the serum phytanic acid level in the biochemical evaluation of the efficiency of the dietary treatment.

Within a family refered here, two sisters are presenting heredopathia atactica polyneuritiformis (Morbus Refsum) with the complete clinical, electromyographical and serological findings (increased phytanic acid level, accumulation of mono- and diphytanyl, triglycerides). In addition, some symptoms of Refsum's disease are clinically apparent in the eight year old daughter of one of the patients, but significant principal characteristics are absent (dissociation of the spinal fluid, retinopathia pigmentosa, increased phytanic acid level). The phytanic acid level in the serum of ten clinically normal blood relations (three of which are also obligatory heterozygotes) is normal. In both patients with manifest illness we found not only the usual spinal fluid changes with highly increased protein levels (gammaglobulin, IgA- and IgG-fraction) but also a remarkably large number of macrophages with vacuoles. Within almost two years of keeping to a strict diet with low phytanic acid and phytol content, both patients showed a distinct clinical improvement in parallel with a decrease of the phytanic acid level. Even a temporary increase of the phytanic acid level in one of the patients did not cause clinical relapse. Regarding the biochemical control of the course of the disease, the phytanic acid containing triglycerides proved to be a highly sensitive parameter.