We commend the short-term use of pamidronate in neonatal severe hyperparathyroidism to treat extreme hypercalcaemia and halt hyperparathyroid-driven skeletal demineralisation in preparation for parathyroidectomy. The remarkable degree of phenotypic variation demonstrated remains unexplained without functional studies; this variability highlights the challenge of treating this rare condition.

Heterozygous mutations of the HNF1B gene are the commonest known monogenic cause of developmental kidney disease. Half of patients have a deletion (approximately 1.3 Mb) of chromosome 17q12, encompassing HNF1B plus 14 additional genes. This 17q12 deletion has been linked with an increased risk of neurodevelopmental disorders, such as autism. Here we compared the neurodevelopmental phenotype of 38 patients with HNF1B-associated renal disease due to an intragenic mutation in 18 patients or due to 17q12 deletion in 20 patients to determine whether haploinsufficiency of HNF1B is responsible for the neurodevelopmental phenotype. Significantly, brief behavioral screening in children with the deletion showed high levels of psychopathology and its impact. Eight individuals (40%) with a deletion had a clinical diagnosis of a neurodevelopmental disorder compared to none with an intragenic mutation. The 17q12 deletions were also associated with more autistic traits. Two independent clinical geneticists were able to predict the presence of a deletion with a sensitivity of 83% and specificity of 79% when assessing facial dysmorphic features as a whole. Thus, the 17q12 deletions but not HNF1B intragenic mutations are associated with neurodevelopmental disorders. Hence, the HNF1B gene is not involved in the neurodevelopmental phenotype of these patients. Nephrologists need to be aware of this association to ensure appropriate referral to psychiatric services.

The optimum range for parathyroid hormone (PTH) levels in children with chronic renal failure (CRF) remains undefined. We aimed to determine growth velocity in children with CRF managed with normal PTH levels. We performed a retrospective case note review of 99 children (77 boys), with a glomerular filtration rate (GFR) <41 ml/min per 1.73 m(2), who had at least 2 years of 3-monthly follow-up. The age range at entry was 0.5-6.0 years; data collection was continued until 10 years of age or the commencement of growth hormone or renal replacement therapy. The median GFR was 22 ml/min per 1.73 m(2); over the study period mean serum calcium and phosphate levels were approximately equal to the mid-point of the respective normal ranges. Median PTH levels were equal to the upper limit of the normal range. Height standard deviation score (Ht SDS) at entry was -1.73. During the study period the overall mean change in Ht SDS was +0.3, significantly greater than the no change expected of a normal population ( P=0.004). The median dose of calcium carbonate was 150 mg/kg per day and 1-alpha calcidol 0.015 microg/kg per day. The growth rate was independent of all parameters, including age, PTH levels, the use of enteral feeds, and 1-alpha calcidol prescription. Our results indicate that catch-up growth can occur in infants and children with CRF when medical therapy is aimed at normalizing PTH levels.

Normal range PTH concentrations are appropriate, allowing normal growth in children with CRF managed conservatively. C-PTH may be of clinical significance.