The diagnostic odyssey of a patient with dihydropyrimidinase deficiency: a case report and review of the literature.

Autor:	Albokhari D; Department of Pediatrics, Taibah University College of Medicine, Medina 42353, Saudi Arabia.; King Faisal Specialist Hospital and Research Center, Medina 42523, Saudi Arabia., Alharbi O; Taibah University College of Medicine, Medina 42353, Saudi Arabia., Blesson A; Department of Bone/Osteogenesis Imperfecta, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA., Jain M; Department of Bone/Osteogenesis Imperfecta, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA; jainm@kennedykrieger.org.; Department of Genetic Medicine, Johns Hopkins Medical Institute, Baltimore, Maryland 21205, USA.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2024 Jan 10; Vol. 9 (4). Date of Electronic Publication: 2024 Jan 10 (Print Publication: 2023).
DOI:	10.1101/mcs.a006319
Abstrakt:	Dihydropyrimidinase (DHP) deficiency is an autosomal recessive metabolic disorder caused by biallelic pathogenic variants of DPYS Patients with DHP deficiency exhibit a broad spectrum of phenotypes, ranging from severe neurological and gastrointestinal involvement to cases with no apparent symptoms. The biochemical diagnosis of DHP deficiency is based on the detection of a significant amount of dihydropyrimidines in urine, plasma, and cerebrospinal fluid samples. Molecular genetic testing, specifically the identification of biallelic pathogenic variants in DPYS , has proven instrumental in confirming the diagnosis and facilitating family studies. This case study documents the diagnostic journey of an 18-yr-old patient with DHP deficiency, highlighting features at the severe end of the clinical spectrum. Notably, our patient exhibited previously unreported skeletal features that positively responded to bisphosphonate treatment, contributing valuable insights to the clinical characterization of DHP deficiency. Additionally, a novel DPYS variant was identified and confirmed pathogenicity through metabolic testing, further expanding the variant spectrum of the gene. Our case emphasizes the importance of a comprehensive diagnostic approach using genetic sequencing and metabolic testing for accurate diagnosis. (© 2023 Albokhari et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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