Importance of Molecular Genetic Analysis for Diagnosis and Genetic Counseling in Families with Hyperammonemia and Ornithine carbamoyltransferase Deficiency
Authors:
L. Dvořáková 1; M. Hřebíček 1; H. Vlášková 1; K. Szentiványi 2; J. Zeman 2
Authors‘ workplace:
Ústav dědičných metabolických poruch, 1. lékařská fakulta UK a VFN, Praha
přednosta doc. MUDr. V. Kožich, CSc.
1; Klinika dětského a dorostového lékařství, 1. lékařská fakulta UK a VFN, Praha
přednosta prof. MUDr. J. Zeman, DrSc.
2
Published in:
Čes-slov Pediat 2010; 65 (10): 575-579.
Category:
Original Papers
Overview
Ornithine carbamolytransferase deficiency is a severe X-linked disorder presenting with acute hyperammonemic attacks.
The aim is to present clinical data and results of mutation analysis in 34 patients with ornithine carbamoyltransferase deficiency.
Patients and methods:
Nine males with severe neonatal form of the disease died in first days of life, 14 patients with late onset form manifested in the 2nd–3rd year of life or in pre-school age; one four-year-old boy and one adult male are asymptomatic. Nine heterozygotes developed symptoms of the disease, one of them in the newborn period, the remaining patients in the 2nd–3rd year of life or at the pre-school age. The diagnosis based on evaluation of analyte concentration in blood plasma and urine was confirmed by methods of mutation analysis.
Results:
The results of analyte profiling (ammonia and glutamine/glutamate concentrations in blood serum and orotic acid in urine) did not predict the phenotype and only partially correlated with the actual health state of the patient. Gross deletions and other obviously null mutations were invariably associated with the neonatal form of the disease. Some missense mutations caused neonatal form, while others were associated with late onset of the disease. Mutation analysis in patient’s families showed that affected boys usually inherit OTC mutations from their heterozygous clinically unaffected mothers, while de novo mutations occur more frequently in manifestingheterozygotes.
Conclusions:
OTC deficiency is a severe disease in which precise and fast diagnosis plays an important role. Molecular genetic diagnosis is essential for confirmation of the diagnosis, genetic counseling and possible prenatal diagnosis in affected families.
Key words:
urea cycle, OTC deficiency, mutation analysis, genotype-phenotype correlation, de novo mutation
Sources
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Labels
Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
2010 Issue 10
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