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.