Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil
Abstract Tetrahydrobiopterin (BH4) 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 th...
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doaj-7b828b4eb5b847499bedf6164e4f39a52021-09-02T07:18:38ZengWileyJIMD Reports2192-83122021-09-01611192410.1002/jmd2.12224Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in BrazilCharles Marques Lourenço0Janaina Dovidio1Isabela F. Lopes2Laís C. Silva3Marcela Almeida4Laura Vagnini5Jacqueline Fonseca6Zumira A. Carneiro7Beat Thöny8Centro Universitário Estácio de Ribeirão Preto São Paulo BrazilCentro Universitário Estácio de Ribeirão Preto São Paulo BrazilCentro Universitário Estácio de Ribeirão Preto São Paulo BrazilCentro Universitário Estácio de Ribeirão Preto São Paulo BrazilCentro Universitário Estácio de Ribeirão Preto São Paulo BrazilCentro Paulista de Diagnóstico e Pesquisa em Genética Clínica São Paulo BrazilLaboratório DLE Bioquímica Genética Rio de Janeiro BrazilCentro Universitário Estácio de Ribeirão Preto São Paulo BrazilDivision of Metabolism University Children's Hospital Zürich SwitzerlandAbstract Tetrahydrobiopterin (BH4) 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 BH4 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.https://doi.org/10.1002/jmd2.12224BH4 deficiencydihydropteridine reductase (DHPR) genehyperphenylalaninemial‐DOPAtetrahydrobiopterin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Charles Marques Lourenço Janaina Dovidio Isabela F. Lopes Laís C. Silva Marcela Almeida Laura Vagnini Jacqueline Fonseca Zumira A. Carneiro Beat Thöny |
spellingShingle |
Charles Marques Lourenço Janaina Dovidio Isabela F. Lopes Laís C. Silva Marcela Almeida Laura Vagnini Jacqueline Fonseca Zumira A. Carneiro Beat Thöny Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil JIMD Reports BH4 deficiency dihydropteridine reductase (DHPR) gene hyperphenylalaninemia l‐DOPA tetrahydrobiopterin |
author_facet |
Charles Marques Lourenço Janaina Dovidio Isabela F. Lopes Laís C. Silva Marcela Almeida Laura Vagnini Jacqueline Fonseca Zumira A. Carneiro Beat Thöny |
author_sort |
Charles Marques Lourenço |
title |
Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil |
title_short |
Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil |
title_full |
Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil |
title_fullStr |
Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil |
title_full_unstemmed |
Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil |
title_sort |
sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: insight from the first case with molecular diagnosis in brazil |
publisher |
Wiley |
series |
JIMD Reports |
issn |
2192-8312 |
publishDate |
2021-09-01 |
description |
Abstract Tetrahydrobiopterin (BH4) 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 BH4 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. |
topic |
BH4 deficiency dihydropteridine reductase (DHPR) gene hyperphenylalaninemia l‐DOPA tetrahydrobiopterin |
url |
https://doi.org/10.1002/jmd2.12224 |
work_keys_str_mv |
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