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Título

Molecular analysis of patients with clinical suspicion of Acute Hepatic Porphyria from a tertiary center in Brazil

Resumo

Introduction:
Acute hepatic porphyrias (AHP) consist in acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP) and porphyria due to delta-aminolevulinic acid deficiency dehydratase (ALAD). Data from USA indicate that the most common is AIP, followed by VP and HCP. Epidemiological data from Brazil are scarce due to lack of available specific biochemical exams and genetic studies.
Objectives:
To describe epidemiological and genetic profile of patients with AHP in a tertiary center in Brazil.
Methods:
We included patients based on clinical history: recurrent abdominal pain, altered colored urine and peripheral or central nervous system manifestation. We reviewed medical records and evaluated all patients. We performed a next generation sequencing panel using a commercial kit.
Results:
We identified 34 suspected patients from 26 different families. Age varied from 18 to 80, median age of 43 years. Majority of patients were female (25/34). 21 patients identified as being white and 13 patients as brown. A total of 26 patients underwent genetic testing. AIP was diagnosed in seven patients from four families, VP was diagnosed in nine patients from five families. Two patients had inconclusive tests and eight patients had a negative panel.
Regarding AIP, each family had a different pathogenic mutation: 973C>T (p.Arg325*); c518G>A (p.Arg173Gln); deletion of exon 1; and a splice donor variant (c.912+2T>C).
For VP, four families shared the same missense variant in exon 6, c503G>A (p.Arg168His), and one patient had a deletion in exon 5-6. Five out of nine patients with VP identified as brown, and four out of seven with AIP, as white. We also identified seven cases of pathogenic intronic variant for erythropoietic porphyria (c.315-48T>C), in six of them associated with AHP.
Conclusion:
Our data suggest that VP is more common in our population than previously reported. This may be related to our country’s history and colonization. VP originated in South Africa, whereas AIP originated in Scandinavia and Northern Europe. More studies are necessary to confirm this epidemiological pattern.

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Doenças Neuromusculares