Dual Diagnosis of Dihydropyrimidine Dehydrogenase Deficiency and GM1 Gangliosidosis

Abstract 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 c...

Full description

Saved in:
Bibliographic Details
Published in:Pediatric neurology 2012-03, Vol.46 (3), p.178-181
Main Authors: Ong, Min T., MB, ChB, Chow, Gabriel C.S., MD, Morton, Richard E., BA, BM, BCh
Format: Article
Language:English
Subjects:
Biological and medical sciences
Brain - pathology
Dihydropyrimidine Dehydrogenase Deficiency - complications
Dihydropyrimidine Dehydrogenase Deficiency - diagnosis
Diseases of striated muscles. Neuromuscular diseases
Female
Gangliosidosis, GM1 - complications
Gangliosidosis, GM1 - diagnosis
Humans
Infant
Magnetic Resonance Imaging
Medical sciences
Nerve Fibers, Myelinated - pathology
Neurology
Pediatrics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract 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 15 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 GM1 gangliosidosis. Mutation analysis confirmed c.841C>T (p.His281Tyr) homozygosity for GM1 gangliosidosis. She died at age 19 months.
ISSN:0887-8994
1873-5150
DOI:10.1016/j.pediatrneurol.2011.12.005