Cold Spring Harbor Molecular Case Studies · 4 authors, 5 centres
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This case report describes a patient with dihydropyrimidinase (DHP) deficiency caused by a novel homozygous DPYS variant (c.502T > C; p.Tyr168His), who presented with severe neurological involvement and was diagnosed through integration of next-generation sequencing and metabolic testing. A review of 35 documented patients highlights wide phenotypic variability, with neurological abnormalities being the most common feature.
The initial chromosomal microarray was negative because it cannot detect copy-neutral changes such as uniparental disomy; diagnosis was ultimately achieved through clinical exome sequencing and biochemical confirmation via gas chromatography–mass spectrometry showing significant urinary DHT and DHU. The authors reviewed 35 documented DHP deficiency patients, finding neurological abnormalities as the most prevalent manifestation, followed by gastrointestinal involvement. This case expands the known DHP phenotype with vertebral osteoporosis and scoliosis. Implications include the need for pyrimidine degradation screening in patients with unexplained neurological symptoms and awareness of 5-FU neurotoxicity risk.
