“Porphyria Plus”: Siblings with Homozygous Variegate Porphyria, a Complex Developmental Disorder and Hypomyelination

Background: Neuropediatric textbooks and literature rarely cover the fact that genetic porphyrias, in their homozygous form, can lead to the clinical picture of a neurodevelopmental disease and that the latter may even be the predominant presentation.

Methods and Results: We present a boy, who was referred to us because of his developmental delay, an epilepsy and a hypomyelination. Additionally, he presented with short stature and microcephaly. Skin lesions, which existed for some time, had been considered as unrelated before. At the same time, skin lesions of his newborn sister were diagnosed as porphyria. This finally led to the molecular genetic testing of both children, which revealed a homozygous mutation (previously not reported) in the PPOX gene, which corresponds to a variegate porphyria. Throughout the next months, the sister also showed a global developmental delay and an epilepsy. Interestingly, magnetic resonance imaging revealed a distinctive hypomyelination in both children.

Discussion: In children with developmental disorder of unknown cause, early childhood epilepsy and growth retardation, detailed dermatological anamnesis, and diagnostic investigations might be beneficial. An abnormal light-sensitive or fragile skin may indicate a genetic porphyria. Some type of porphyria (especially variegate porphyria and acute intermittent porphyria) can in the homozygous form involve neurodevelopmental disorders. Accordingly, biochemical and, where appropriate, genetic examinations are recommended.