Mortality in children with classic congenital adrenal hyperplasia and 21-hydroxylase deficiency (CAH) in Germany.
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ABSTRACT: Background
Adrenal crises in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) are life-threatening and have the potential to death.Methods
A survey was performed among Paediatric Endocrinologists in Germany to report on deceased children with CAH. Our survey covered the whole of Germany.Results
The participating centres reported 14 cases of death (9 female, 5 male) from 1973 until 2004, but no deaths thereafter. 11 children had the SW form and 3 the simple virilizing (SV) form. All patients were on glucocorticoid replacement, and the SW forms additionally on mineralocorticoid replacement. The age at death varied between 6 weeks and 16.5 years. Seven children died before introduction of general neonatal screening, and 7 children thereafter. Before death, the clinical signs of impending crisis were nonspecific. Five patients developed hypoglycaemia and convulsions with cerebral oedema. Half of the deceased patients died at home. The hydrocortisone dosage was only doubled in two of the 14 cases.Conclusions
According to the assessments by the attending centres, almost all deaths could be related to an inadequate administration of stress doses of hydrocortisone. Since no deceased CAH children were reported in Germany from 2005 on, we assume the effectiveness of educational programs over the past years.
SUBMITTER: Dorr HG
PROVIDER: S-EPMC5994009 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGenetic analysis is commonly performed in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency.Study objectiveThe objective of the study was to describe comprehensive CYP21A2 mutation analysis in a large cohort of CAH patients.MethodsTargeted CYP21A2 mutation analysis was performed in 213 patients and 232 parents from 182 unrelated families. Complete exons of CYP21A2 were sequenced in patients in whom positive mutations were not identified by targeted mutation analysis. Copy number variation and deletions were determined using Southern blot analysis and PCR methods. Genotype was correlated with phenotype.ResultsIn our heterogeneous U.S. cohort, targeted CYP21A2 mutation analysis did not identify mutations on one allele in 19 probands (10.4%). Sequencing identified six novel mutations (p.Gln262fs, IVS8+1G>A, IVS9-1G>A, p.R408H, p.Gly424fs, p.R426P) and nine previously reported rare mutations. The majority of patients (79%) were compound heterozygotes and 69% of nonclassic (NC) patients were compound heterozygous for a classic and a NC mutation. Duplicated CYP21A2 haplotypes, de novo mutations and uniparental disomy were present in 2.7% of probands and 1.9 and 0.9% of patients from informative families, respectively. Genotype accurately predicted phenotype in 90.5, 85.1, and 97.8% of patients with salt-wasting, simple virilizing, and NC mutations, respectively.ConclusionsExtensive genetic analysis beyond targeted CYP21A2 mutational detection is often required to accurately determine genotype in patients with CAH due to the high frequency of complex genetic variation.
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