PD13 Severe cutaneous manifestations in an Indian child with X-linked dominant erythropoietic protoporphyria

Abstract Erythropoietic protoporphyria (EPP) is usually caused by autosomal dominant mutations in FECH: raised protoporphyrin levels cause itching, burning and erythema after sun exposure, with facial scarring sometimes liver damage. We report a child the much rarer X-linked form (XLDPP) consider reasons for his unusually severe features. A 4-year-old boy living India presented long-standing erosions on face sides of feet, marked distal onycholysis subungual hyperkeratosis affecting all nails, suggestive pachyonychia congenita (PC). There was no relevant family history or parental consanguinity. He anaemic (haemoglobin 7.2 g dL−1). Genetic testing revealed variants PC genes, but there hemizygous deletion ALAS2, c.1706_1709del (p.Glu569GlyfsT er24) reported recurrently XLDPP. Further review photosensitivity, low vitamin D3 enzymes. Measurement erythrocyte not available, XLDPP diagnosed basis abnormalities, probable photo-onycholysis genetic testing. ALAS2 encodes 5-aminolaevulinate synthase, first enzyme haem synthetic pathway. Most block haemoglobin production resulting sideroblastic anaemia. However, specific deletions, including this one, activate pathway, increasing to higher than what can be used haematopoiesis. The manifestations therefore resemble EPP: accumulation former increased latter its conversion haem. Iron deficiency, common Indian children, reduces consequently utilization, potentially exacerbating In previous patient anaemia due gastrointestinal bleeding, iron therapy successfully lowered red cell (Whatley SD, Ducamp S, Gouya L et al. C-terminal deletions gene lead gain function without anemia overload. Am J Hum Genet 2008; 83:408–14). Nail dystrophy has previously been appearance here consistent whose feet are always exposed sandals. delay diagnosing photosensitivity severity skin changes attributed difficulty interpreting symptoms young children local conditions where exposure unavoidable. Management involves therapy, photoprotection, monitoring counselling; female carriers may also have symptoms. grateful national experts helpful discussion case.