Gain-of-function mutations in the calcium-sensing receptor are associated with a familial syndrome of hypocalcemia with hypercalciuria that needs to be distinguished from hypoparathyroidism.

Conclusions-Linking national surveillance with a specialised laboratory service allowed estimation of HUS incidence and provided information on its aetiology. In contrast to North America, Japan, and the British Isles, STEC O157:H7 is rare in Australia; however, non-O157:H7 STEC cause severe disease including outbreaks. Disease severity in outbreak cases may relate to yet unidentified virulence factors of the O111:H− strain isolated. (Arch Dis Child 2001;85:125-131)

The cardiac abnormalities that complicate chronic renal failure and renal replacement therapy are not well characterized in young people. These abnormalities are becoming more important because successful renal transplantation has resulted in children with end-stage renal failure living longer. Echocardiographic abnormalities of cardiac function and structure were studied in children and young adults (< 27 years old) with chronic renal failure (CRF, N = 32), end-stage renal failure treated with chronic peritoneal dialysis (CPD, N = 10) or renal transplantation (N = 30) or controls (N = 60). Left ventricular mass indexed for height (LVM/Ht and LVM/Ht2.7) and body surface area (LVM/SA), fractional shortening, measurement of left ventricular diastolic function (peak E and A wave velocities and the EA ratio) and structural (such as valvular) abnormalities were determined by echocardiography. The median (and range) of LVM/Ht in the groups were control 51.8 (23.1 to 119.8), CRF 60.2 (22.2 to 135.8), CPD 80.2 (14.5 to 100.9) and transplant group 97.8 (51.2 to 182.1) g/m. The increases in LVM/Ht, LVM/Ht2.7 and LVM/SA in the transplant group were significant (P < 0.01). The CRF group had significantly increased LVM/Ht2.7 and LVM/SA (P < 0.01). Systolic function was not significantly different between the groups. A significant correlation between creatinine and LVM indexed for height was found in the CRF group. Systolic or diastolic blood pressure could not be correlated with LVM indices in the transplant group. Changes in diastolic function were found (increased peak A wave velocity and decreased E/A ratios in the CRF and CPD groups, and increased peak E wave velocity in the transplant group). The study demonstrated that left ventricular hypertrophy is a frequent and often severe finding in children with chronic renal failure and those treated with renal replacement therapy. Factors other than hypertension and anaemia are important, and evidence was found for a link between serum creatinine and increased left ventricular mass prior to end-stage renal failure.

Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are two related conditions caused by mutations of the Wilms tumor gene, WT1. Both syndromes are characterized by male pseudohermaphroditism, a progressive glomerulopathy, and the development of genitourinary tumors. DDS and FS have previously been distinguished by differences in nephropathy, with DDS patients demonstrating diffuse mesangial sclerosis (DMS) in contrast to focal and segmental glomerulosclerosis (FSGS) in FS patients. The clinicopathological features and genotype analysis of two patients with WT1 mutations are presented in this report. Genotype analysis of the first patient revealed a previously undescribed mutation in exon 8 of the WT1 gene. The second patient presented with a rapidly progressive nephropathy characterized histologically by DMS, but was found to have the genetic mutation seen in FS patients. A summary of all reported patients with the characteristic mutation associated with FS demonstrates the clinical overlap of this syndrome with DDS. This suggests that both these conditions should be considered as part of the spectrum of disease due to WT1 gene mutations rather than as separate diseases. Clinical classification remains important for prognosis, as the underlying renal disease appears to predict the progression of nephropathy independently of the genetic abnormality.

SUMMARY Escherichia coli 0157:H7 was isolated from a fatal case of haemorrhagic colitis with haemolytic uraemic syndrome and neurological symptoms. This strain induced diarrhoea and neurological symptoms including incoordination, ataxia, and convulsions in piglets after oral inoculation. Similar neurological signs were seen in piglets inoculated intraperitoneally with bacterial extracts containing a shiga-like toxin that is elaborated by the bacteria. Histological examination of the brains from these piglets showed vascular damage and small infarcts confined to the cerebellum. Comparable lesions were also seen in the brain of the child from whom E coli 01 57:H7 was isolated. We suggest that the cerebral changes in the piglets and in the patient were caused by the shiga-like toxin elaborated by E coli 0157:H7. The shiga-like toxin is thought to cause neurological abnormalities by damage to cerebral blood vessels rather than by a direct effect on the neurones.