Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil.

Autores da FMUP

• João De Almeida Lopes Da Fonseca

  Autor

Participantes de fora da FMUP

• Lourenço CM
• Dovidio J
• Lopes IF
• Silva LC
• Almeida M
• Vagnini L
• Carneiro ZA
• Thöny B

Unidades de investigação

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Medicina da Comunidade, Informação e Decisão em Saúde

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Tetrahydrobiopterin (BH(4)) is a cofactor that participates in the biogenesis reactions of a variety of biomolecules, including l-tyrosine, l-3,4-dihydroxyphenylalanine, 5-hydroxytryptophan, nitric oxide, and glycerol. Dihydropteridine reductase (DHPR, EC 1.5.1.34) is an enzyme involved in the BH(4) regeneration. DHPR deficiency (DHPRD) is an autosomal recessive disorder, leading to severe and progressive neurological manifestations, which cannot be exclusively controlled by l-phenylalanine (l-Phe) restricted diet. In fact, the supplementation of neurotransmitter precursors is more decisive in the disease management, and the administration of sapropterin dihydrochloride may also provide positive effects. From the best of our knowledge, there is limited information regarding DHPRD in the past 5 years in the literature. Here, we describe the medical journey of the first patient to have DHPRD confirmed by molecular diagnostic methods in Brazil. The patient presented with two pathogenic variants of the quinoid dihydropteridine reductase (QDPR) gene-which codes for the DHPR protein, one containing the in trans missense mutation c.515C>T (pPro172Leu) in exon 5 and the other containing the same type of mutation in the exon 7 (c.635T>C [p.Phe212Ser]). The authors discuss their experience with sapropterin dihydrochloride for the treatment of DHPRD in this case report.

© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.

Keywords

• BH4 deficiency; dihydropteridine reductase (DHPR) gene; hyperphenylalaninemia; l-DOPA; tetrahydrobiopterin