Dual Diagnosis of Dihydropyrimidine Dehydrogenase Deficiency and Gm(1) Gangliosidosis

An 8-month-old girl, born to consanguineous parents, presented with developmental delay, decreased muscle tone, disinterest in her surroundings, and sleepiness. Tests revealed a marked excretion of thymine with significantly increased uracil excretion in the urine, indicating a pyrimidine catabolic disorder, i.e., dihydropyrimidine dehydrogenase deficiency. Plasma endogenous purines confirmed elevated plasma thymine (21 μmol/L) and uracil (29 μmol/L), also consistent with dihydropyrimidine dehydrogenase deficiency. Purine mutation analysis confirmed complete dihydropyrimidine dehydrogenase deficiency with a 16 [ corrected] base pair homozygous deletion in exon 16, corresponding to DPYD c.2043-2058del. Cranial magnetic resonance imaging at 14 months indicated severe hypomyelination with gliosis. Her basal ganglia were also involved. At age 15 months, she was hospitalized for aspiration pneumonia and seizures, and also manifested hepatosplenomegaly. White cell enzymes revealed a marked deficiency of β-galactosidase activity (4 μmol/g/hour) in white cells and an elevated chitotriosidase activity (443 μmol/L/hour) in plasma indicating GM(1) gangliosidosis. Mutation analysis confirmed c.841C>T (p.His281Tyr) homozygosity for GM(1) gangliosidosis. She died at age 19 months.