Genetic landscape of phenylketonuria in Brazil.

IF 3.6 2区医学 Q2 GENETICS & HEREDITY

Orphanet Journal of Rare Diseases Pub Date : 2026-07-09 DOI:10.1186/s13023-026-04435-x

Rafael Hencke Tresbach, João Braga de Abreu Neto, Fernanda Sperb-Ludwig, Marta Wey Vieira, Roseli Divino Costa, Pedro Eduardo Bonfim Freitas, Luiz Carlos Santana da Silva, Louise Lapagesse de Camargo Pinto, Marcial Francis Galera, Keyla Christy Christine Mendes Sampaio Cunha, Cezar Antonio Abreu de Souza, José Nélio Januário, Marcos José Burle Aguiar, Romina Soledad Heredia, Maria Teresa Alves da Silva Rosa, Monique Oliveira Poubel, François Maillot, Ida Vanessa Doederlein Schwartz

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引用次数: 0

Abstract

Phenylketonuria (PKU), one of the most common inherited metabolic disorders, is caused by biallelic loss-of-function variants in the phenylalanine hydroxylase (PAH) gene. More than 1000 pathogenic variants have been described in this gene. Although genotype-phenotype correlations are imperfect, PAH genotypes can influence treatment decision-making. To better characterize the genetic landscape of PKU in Brazil, we compiled a dataset of PAH genotypes from 742 patients by combining data from the literature (n = 486), public databases (n = 117), and direct physician reports (n = 139). Most patients were classified as having classical PKU (n = 455/742; 61.3%). The most prevalent variants were c.1162G > A (16.6%), c.1066-11G > A (13.9%), and c.782G > A (11.8%), which are also the predominant ones in Portugal, Spain, and Latin America. This study confirms the allelic heterogeneity of PKU in the Brazilian population and provide relevant insights to support public health policies for this disorder.

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巴西苯丙酮尿症的遗传景观。

苯丙酮尿症（PKU）是最常见的遗传性代谢疾病之一，是由苯丙氨酸羟化酶（PAH）基因的双等位基因功能丧失变异引起的。该基因有1000多种致病变异。虽然基因型与表型的相关性并不完善，但PAH基因型可以影响治疗决策。为了更好地描述巴西PKU的遗传景观，我们通过结合文献（n = 486）、公共数据库（n = 117）和直接医生报告（n = 139）的数据，编制了来自742名患者的PAH基因型数据集。大多数患者被归类为经典PKU （n = 455/742; 61.3%）。c.1162G > A（16.6%）、c.1066-11G > A（13.9%）和c.782G > A（11.8%）是最常见的变异，在葡萄牙、西班牙和拉丁美洲也占主导地位。本研究证实了巴西人群中PKU的等位基因异质性，并为支持该疾病的公共卫生政策提供了相关见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Orphanet Journal of Rare Diseases 医学-医学：研究与实验

CiteScore

6.30

自引率

8.10%

发文量

418

审稿时长

4-8 weeks

期刊介绍： Orphanet Journal of Rare Diseases is an open access, peer-reviewed journal that encompasses all aspects of rare diseases and orphan drugs. The journal publishes high-quality reviews on specific rare diseases. In addition, the journal may consider articles on clinical trial outcome reports, either positive or negative, and articles on public health issues in the field of rare diseases and orphan drugs. The journal does not accept case reports.