Daniah Albokhari1,2, Ohood Alharbi3, Alyssa Blesson4 and Mahim Jain4,5 1Department of Pediatrics, Taibah University College of Medicine, Medina 42353, Saudi Arabia; 2King Faisal Specialist Hospital and Research Center, Medina 42523, Saudi Arabia; 3Taibah University College of Medicine, Medina 42353, Saudi Arabia; 4Department of Bone/Osteogenesis Imperfecta, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA; 5Department of Genetic Medicine, Johns Hopkins Medical Institute, Baltimore, Maryland 21205, USA Corresponding author: jainmkennedykrieger.org Abstract

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.

Received September 9, 2023. Accepted December 5, 2023.