The aim of this report was to describe childhood patients with Wegener granulomatosis (WG) from one centre, to analyse the variety of clinical manifestations seen and compare the data with other published paediatric and adult series. The records of 17 patients with WG who were under the care of Great Ormond Street Hospital for Children (GOSH) from 1981 to 1998 were reviewed. We analysed presenting features before admittance to GOSH and the clinical signs observed whilst the children were under the care of the hospital. Of 17 patients, 13 were females and there was a male/female ratio of 1:3.25. Among the patients there were 2 sisters. The age of the patients at disease onset varied from 2 weeks to 14 years. The median/mean age was 6/6.3 years. American College of Rheumatology criteria for diagnosing WG were fulfilled in 11 of 17 patients. The frequency of different system involvement was: respiratory 87%, kidneys 53%, sinuses 35%, joints 53%, eyes 53%, nervous system 12%, skin 53%. cANCA was positive in 10 patients (59%), but pANCA was negative in all measured sera. Kidneys were involved in 2 of 8 patients (25%) with the disease onset from 0 to 5 years and in 7 of 9 patients (78%) with the disease onset from 6 to 14 years ( P<0.05). cANCA was positive in 7 of 9 patients with kidney disease (78%) and in 2 of 8 patients (25%) without kidney involvement ( P<0.05). Colchicine as a supplement to prednisolone and cytotoxic/immunosuppressant drugs was used effectively in 5 patients.

Steroid-sensitive nephrotic syndrome (SSNS) accounts for .80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68310 26 (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and #589 controls; P=1.42310 217). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825310 25). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS.

No abstract

A high proportion of renal patients were vitamin D deficient/insufficient, particularly children of South Asian origin. High PTH values in the setting of reduced GFR might be due to vitamin D deficiency and should lead to estimation of serum 25(OH)D concentration.

Sirs,We read with great interest the study by Menon et al. regarding concentrations of serum 25-hydroxyvitamin D [25(OH)D; a measure of body stores of vitamin D] and hyperparathyroidism in children with chronic kidney disease [1]. The authors found that 77.2% of their patients with chronic kidney disease were vitamin D deficient/ insufficient, as defined by serum 25-hydroxycholecalciferol [25(OH)D3] levels of less than 30 ng/ml. Twenty-two of these patients received treatment with ergocalciferol, based on their serum 25(OH)D3 levels and in accordance with the guidelines of the Kidney Disease Outcomes Quality Initiative (KDOQI) [2]. Patients with vitamin D insufficiency [25(OH)D3 levels between 16 ng/ml and 30 ng/ml] were given ergocalciferol 2,000 IU daily for 12 weeks. Those who had 25(OH)D3 levels between 5 ng/ml and 15 ng/ml received ergocalciferol 4,000 IU daily for 12 weeks [2]. Parathyroid hormone (PTH) levels were noted to have fallen when checked 3 months after commencement of the ergocalciferol treatment.We have previously reported very similar findings in a study of 143 children with renal disease from our large tertiary referral centre in the north of the UK (latitude 53°26′) [3]. Of the children attending our outpatient clinics, 58% were vitamin D deficient/insufficient, defined as 25(OH)D3 levels of less than 20 ng/ml. A total of 83.2% had levels below 30 ng/ml, a value very similar to that reported in the study by Menon and colleagues, indicating the high prevalence of this problem on both sides of the Atlantic.It is well known that adherence to treatment is a major problem in children with kidney disease, particularly among adolescents [4]. Because there have been previous problems with significant non-adherence to prescribed therapy, we have recently changed our practice regarding the administration of ergocalciferol to vitamin D-deficient patients. We currently use a single large dose (100,000 IU for those 5-10 years of age and 150,000 IU for those over 10 years old), ingestion being witnessed in the outpatient clinic by the nephrologist or clinic nurse. The procedure is repeated every 3 months as necessary, according to 25 (OH)D3 levels. We have not used this regimen in children under 5 years of age, in whom adherence to treatment is less of a problem. Twenty children with very low levels of vitamin D [25(OH)D3 concentration of less than 16 ng/ml] were given a single dose of ergocalciferol. Their mean [standard deviation (SD)] age was 13.6± 3.4 years, with a range of 6-17 years. Baseline serum 25 (OH)D [25(OH)D2+25(OH)D3] levels were 1.5-15.8 ng/ ml [mean (SD) 8.1±3.4 ng/ml]. Three months after singledose treatment, measurement of the 25(OH)D levels was repeated and showed a significant rise to 7-25.6 ng/ml [mean (SD) 18.2±5.0 ng/ml, P<0.00001]. These results are presented in Fig. 1. The specific measurement of vitamin D2 concentrations, performed to determine the specific effect of the orally administered vitamin D2, showed an increase from 0 ng/ml (as none of our patients had been receiving vi...