The importance of semiology and biochemistry in the diagnostic management of a peroxisomal biogenesis disorder
Introduction. Peroxisomal biogenesis disorders are due to mutations in the PEX genes, which code for peroxins that are required for peroxisomal biogenesis. Clinically, they are expressed as a Zellweger syndrome spectrum, and there is a wide phenotypic variety. They are diagnosed biochemically, and confirmation is molecular. The aim of this illustrative case is to highlight the importance of the clinical features and biochemical testing in the management of a peroxisomal disease.
Case report. A 3-year-old boy with neonatal hypotonia, overall developmental delay and failure to thrive and a pattern of hypomyelinating leukodystrophy in brain resonance. The suspected diagnosis was a disorder affecting the biogenesis of the peroxisomes due to having found a variant with an uncertain meaning in PEX5. The clinical features, the biochemical studies and critical analysis, however, made this diagnosis unlikely. Emphasis is placed on the management that must be applied when a Zellweger syndrome spectrum is suspected.
Conclusion. In the case reported here, a peroxisomal biogenesis disorder was suspected owing to an exome sequencing which, on being critically analysed together with the clinical features and the biochemical findings, made a peroxisomal disease very unlikely. In cases of clinical suspicion, backed up by neuroimaging, the main diagnostic management must be based on the biochemistry analysis. Although confirmation is molecular, these tests must be interpreted with caution.
Key words. Hypomyelination. Leukodystrophy. Peroxisomal biogenesis disorder. PEX genes. Zellweger syndrome spectrum.