Molecular Differential Diagnosis in a Severe Case of Atypical Cutaneous Porphyria Identifies a New Mutational Variant in the FECH Gene

COLOMBO, FEDERICO; MELITO, VIVIANA; GRANATA, BARBARA XOANA; ROSSETTI, MARIA VICTORIA; BATLLE, ALCIRA; PARERA, VICTORIA

Lucerna

Congreso; INTERNATIONAL CONGRESS ON PORPHYRINS AND PORPHYRIAS 2013; 2013

Porphyrias are disorders of haem metabolism, as a result of a primary and partial deficiency of one of the seven enzymes in the pathway, after the first and regulatory enzyme ALA-S. As a consequence, precursors ALA and PBG and/or porphyrins accumulate, leading to the typical clinical and biochemical signs. According to the symptoms, Porphyrias are classified in Cutaneous, Acute and Mixed. Generally, differential diagnosis is achieved by biochemical determinations and later, molecular studies allow us to detect the mutation responsible for the porphyria in each patient, then, presymptomatic diagnosis in their relatives can be obtained. A 31 years old patient with severe cutaneous manifestations: bullous, hyperpigmentation, cutaneous fragility, photosensitivity, hyperthricosis, ocular and nail lesions, without acute symptoms, was directed to our Center for attention. Biochemical studies revealed a plasma porphyrin index characteristic for Variegate Porphyria (VP): 9.81, ¦Ë = 626; NV: ¡Ü 1.30, ¦Ë = 618, and elevated excretion of fecal porphyrins: 1,051 ¦Ì g/gdw, VN: ¡Ü 130 ¦Ì g/gdw, but with an excretion profile characteristic of Erythropoietic Protoporphyria (EPP). In the case of these patients, with atypical presentation, genetic study is necessary for the differential diagnosis. Mutations in PPox and FECH genes, responsible of VP and EPP respectively, were looked for. No mutation was detected in the PPox gene, but a new genetic variant was found in the FECH gene: c.77 G > A, generating a missense mutation in codon 26 of exon 2 (p.S26N), associated in trans to the low expression haplotype: c.1-251 G, c.68-23 T, c.315- 48 C, according to the autosomic dominant form with incomplete penetrance of EPP. To exclude that the genetic variant c.77 G > A (p.S26N) was a common polymorphism, it was screened in 200 chromosomes from control volunteers and all of them presented the c.77G allele. Our results confirmed, once more, the importance of reaching the correct differential diagnosis of the Porphyria, allowing then to use the proper therapy for the patient and also the familial presymptomatic diagnosis..