Molecular detection of genetic defects in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: A study of 27 families

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OHase) deficiency is inherited as an autosomal recessive trait. Patients can present with the salt wasting, simple virilizing or a non-classical form of the disease. The gene for P450C21, the enzyme carrying 21-OHase activity, has been mapped to the major histocompatibility complex on chromosome 6p. Using molecular hybridisation techniques we have studied the genetic defect in 27 families with one or more affected off-spring diagnosed and treated at the University Hospital of Essen. DNA samples were digested with restriction endonucleaseTaqI,PvuII,BglII, andEcoRI and analysed by Southern blot hybridisation with the cDNA probe pC21/3c. Eleven of 40 haplotypes associated with the salt wasting form were found to have a large deletion of 30 kb affecting the 5 end of the active 21-OHase gene and the 3 end of the closely linked pseudogene. Results in another 11 cases are compatible with gene conversion; 18 cases were not informative. The 30 kb deletion was associated with a combination of the HLA antigens Bw47 and DR7 in 7 of 11 cases. In the haplotypes with gene conversion, no linkage disequilibrium to HLA antigens was found. No apparent gene alterations were detected in simple virilizing and non-classical haplotypes. The direct detection of the genetic defect in 55% of the salt wasting haplotypes may help to improve predictive testing in families with CAH.     

Severe hypoaldosteronism due to corticosterone methyl oxidase type II deficiency in two boys: metabolic and gas chromatography-mass spectrometry studies

Infection-triggered, life-threatening salt-loss and hyperkalaemia developed in two male infants with wasting, inappropriately low plasma aldosterone concentrations and elevated plasma renin activity. The presumptive diagnosis of a defective terminal step in aldosterone biosynthesis was made by the presence of large amounts of 11-dehydrotetrahydrocorticosterone and its 18-hydroxylated metabolite (18-OH-THA), free 18-hydroxycorticosterone (18-OH-B) and 18-hydroxytetra-hydrocorticosterone in the urine of both patients. The diagnosis of corticosterone methyl oxidase type II (CMO II) deficiency was confirmed by an elevated urinary 18-OH-THA to tetrahydroaldosterone ratio in one boy and by an elevated plasma 18-OH-B to aldosterone ratio in the other boy. Unknown steroids responsible for the salt-loss were not identified. Sodium supplementation but not short-term high dose oral 9-fluorcortisol (FF) normalized the hyponatraemia in one patient, in whom sodium (Na⁺)/potassium (K⁺) co-transport was decreased. Both patients eventually received long-term FF treatment to prevent impairment of longitudinal growth caused by chronic salt-loss. The diagnosis of CMO II deficiency should always be confirmed by elevated precursor-product ratios in urine or plasma, using radioimmunoassays with prior chromatographic separation. Metabolic studies as the short-term response of serum Na⁺ to high dose FF may not be helpful in differentiating aldosterone biosynthetic defects from endorgan resistance to mineralocorticoids.Dedicated to Professor Dr. Walter Teller, on the occasion of his 60th birthdayPresented in part at the 27th Annual Meeting of the European Society for Paediatric Endocrinology, Copenhagen, Denmark, June 1988     

Wachstum bei Störungen der Schilddrüsenfunktion im Kindes- und Jugendalter

Background

Disorders of the thyroid function of mother and child can not only irreversibly inhibit maturation of the central nervous system, but may also affect growth and puberty.

Objectives

Review of the consequences of thyroid function disorders on the growth of children and adolescents and the relevance of adequate treatment.

Materials and Methods

This article summarises the current literature concerning the effect of thyroid hormone disorders of mother and child and their therapy on growth.

Results

Every untreated manifestation of congenital or acquired hypothyroidism is associated with a delay of growth and skeletal maturation. In children presenting with acquired hyperthyroidism, height is shifted towards higher values and skeletal maturation is accelerated. Approximately 20?% of children and adolescents with Down syndrome develop primary hypothyroidism, frequently manifesting within the first months of life (approximately 5.5?%). Adequate treatment of the thyroid disorder can normalise growth disorders. About 6?% of children with growth hormone deficiency develop abnormally low free thyroxin (fT4) levels in serum during growth hormone treatment due to increased conversion of T4 to T3. There is no indication for treatment after excluding secondary hypothyroidism.

Conclusions

Early diagnosis and timely, adequate treatment of thyroid function disorders of mother and child are essential to achieving growth that is as age-appropriate as possible in affected children and adolescents

     

Pulp revascularization for immature replanted teeth: a case report

Immature avulsed teeth are not usually treated with pulp revascularization because of the possibility of complications. However, this therapy has shown success in the treatment of immature teeth with periapical lesions. This report describes the case of an immature replanted tooth that was successfully treated by pulp revascularization. An 8‐year‐old boy suffered avulsion on his maxillary left lateral incisor. The tooth showed incomplete root development and was replanted after 30 minutes. After diagnosis, revascularization therapy was performed by irrigating the root canal and applying a calcium hydroxide paste and 2% chlorhexidine gel for 21 days. In the second session, the intracanal dressing was removed and a blood clot was stimulated up to the cervical third of the root canal. Mineral trioxide aggregate was placed as a cervical barrier at the entrance of the root canal and the crown was restored. During the follow‐up period, periapical repair, apical closure and calcification in the apical 4 mm of the root canal was observed. An avulsed immature tooth replanted after a brief extra‐alveolar period and maintained in a viable storage medium may be treated with revascularization.