Further Characterization of the Neuroendocrine Phenotype Associated With the PPOX-Related Variegate Porphyria

Background: Variegate porphyria is caused by mutations in the PPOX gene; it usually presents in adolescents and adults as an autosomal dominant condition, with cutaneous features or acute peripheral and/or central nervous system crises. A rarer variant, homozygous variegate porphyria, presents in childhood with cutaneous manifestations as well as neurophenotypes. This study sought to further characterize the homozygous PPOX-related neuroendocrine phenotype.

Methods: This study is a retrospective review of the patients' charts, including their clinical evaluation and molecular genetics, neurodiagnostic, and neuroradiological investigations.

Results: We describe here three children from a consanguineous family who presented with nystagmus, developmental delay and ataxia, photosensitive skin manifestations, and adrenal insufficiency. Analysis of porphyrins in plasma, urine, and stool together with a genetic study of the PPOX gene confirmed the diagnosis. Interestingly, brain MRI showed severe hypomyelination, a finding rarely reported in variegate porphyria, together with adrenal insufficiency.

Conclusion: We recommend analysis of porphyrins in unexplained hypomyelination disorders. Patients with variegate porphyria should be tested for adrenal insufficiency.