Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil.
Charles Marques LourençoJanaina DovidioIsabela F LopesLaís C SilvaMarcela AlmeidaLaura VagniniJacqueline FonsecaZumira A CarneiroBeat ThönyPublished in: JIMD reports (2021)
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.
Keyphrases
- case report
- nitric oxide
- healthcare
- copy number
- intellectual disability
- replacement therapy
- stem cells
- systematic review
- genome wide
- weight loss
- single molecule
- early onset
- gene expression
- autism spectrum disorder
- health information
- protein protein
- binding protein
- small molecule
- blood brain barrier
- dna methylation
- smoking cessation