PEDBASE.org - The Pediatric Database -
Detailed information of OROTIC ACIDURIA
OROTIC ACIDURIA
DEFINITION:
An inborn error of pyrimidine metabolism characterized by an
enzyme deficiency resulting in hematological and neurological
manifestations.
EPIDEMIOLOGY:
- incidence: rare
- age of onset:
- risk factors:
- familial - autosomal recessive
- chrom.#: 3 cen-q21
- gene: uridine 5'-monophosphate (UMP) synthetase
- M = F
PATHOGENESIS:
- a bifunctional enzyme with orotidylic acid pyrophosphorylase
(OMP-PP) and orotidylic acid decarboxylase (OMP-DC) activities
- orotic acid is an intermediate compound in the synthesis of
pyrimidines
2. Genetic Defect
- genetic defect -> deficiency of OMP-PP and/or OMP-DC
activities
- accumulation of orotic acid plus interference with RNA and
DNA synthesis -> hematological manifestations as vigorous
synthesis of RNA and DNA is necessary for normal hematopoiesis
- two clinical types:
CLINICAL FEATURES:
- megaloblastic anemia unresponsive to vitamin C, B12, or
folic acid
2. Neurological Manifestations
- growth retardation
- mental retardation
INVESTIGATIONS:
- deficiency of orotidylic acid pyrophosphorylase and/or
decarboxylase activities in leukocytes, erythrocytes, hepatic
cells and cultured skin fibroblasts
- prenatal - ?
2. Serum
3. Urine
- excessive excretion of orotic acid (up to 1.5 g/day)
- crystalluria
MANAGEMENT:
- no treatment for underlying disorder
- multidisciplinary approach
- Paediatrics, Hematology
- genetic counselling
2. Medical
- lower the urinary excretion of orotic acid and increase
- DNA and RNA synthesis
- oral uridine therapy
2. Corticosteroids
|
Pediatric Database - OROTIC ACIDURIA
Pediatric Organization - Pedbase [at] Gmail.com