Presentation, acute illness, and learning difficulties in salt wasting 21-hydroxylase deficiency.

Abstract

The presentation, pattern of acute illness, and incidence of learning difficulties are described in 63 (33 boys, 30 girls) children with salt wasting 21-hydroxylase deficiency, drawn from a cohort study of congenital adrenal hyperplasia in the South West Region of England between 1968 and 1988. Thirty boys presented with a salt losing crisis from birth whereas the other three boys presented between 2 and 14 months of age with failure to thrive and hyponatraemia. Diagnostic uncertainty led to 13 (43%) of 30 girls developing a salt losing crisis. Five girls were misassigned as boys at birth. There were four deaths in the group, two due to salt losing crisis, one to complications of prematurity possibly compounded by 21-hydroxylase deficiency, and one from heart failure probably related to an excess of steroids. Acute admissions were common, especially during the first year of life, with convulsions in 7% of admissions. The 9% incidence of hypoglycaemia was considered to be an underestimate as blood glucose was measured in only 56 (22%) of 254 admissions. No convulsions occurred in the 38 (15%) admissions where the parents had given intramuscular hydrocortisone before bringing the child to hospital. A high incidence of learning difficulties was found among the 59 surviving children (9/30 (30%) boys and 6/29 (21%) girls), and in only two children could any factor other than 21-hydroxylase deficiency be invoked. Analysis of the subgroup with learning difficulties indicated that they were more ill at presentation with a significantly higher incidence of hypoglycaemia, and that growth in the first year was significantly worse.It is concluded that congenital adrenal hyperplasia remains a formidable disorder with an appreciable mortality and morbidity. The high incidence of learning difficulties seen in salt wasting 21-hydroxylase deficiency needs further attention. A prospective study is indicated to examine the effect of neonatal screening on morbidity from congenital adrenal hyperplasia, particularly the intellectual impairment seen in this study.

Female Preponderance in Congenital Adrenal Hyperplasia due to CYP21 Deficiency in England: Implications for Neonatal Screening

“…It is our experience that there is a considerable delay, on the part of both parents and doctors, between the first signs of the disease and the diagnosis [13]. Furthermore, there is evidence that early electrolyte disturbances may have a permanent detrimental effect on the neuronal development, resulting in learning difficulties [14]. Early detection and diagnosis would benefit patients with milder forms of CYP21 deficiency, because early virilization with its negative psychological consequences and its adverse effect on the final height could be prevented.…”

Neonatal screening for congenital adrenal hyperplasia

“…One benefit of screening could be that the frequency of minor handicaps (learning disabilities and behavioural problems), reported in two retrospective studies in patients, might be decreased (12,13). Another possible benefit is that the frequency of skin problems could be decreased by screening, according to a prospective study showing more skin problems at the age of two years in patients with severe salt wasting postnatally (34).…”

“…6.5 mmol/l) was present in all patients from 11 days after birth (2). Besides the life-threatening short-term consequences, salt wasting may also have long-term effects, such as learning disabilities and behavioural problems (12,13).…”

Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life

“…However, thus far, little has been published about the success of crisis prevention in the years after detection by screening. Most reports on adrenal crises or clinical outcomes concern CAH patients who were born before the introduction of CAH neonatal screening (12,13). Among the few studies on adrenal crises in patients with multiple causes of adrenal insufficiency (14,15), there is only one study exclusively concerning CAH patients (16).…”