Shiga toxin-producing Escherichia coli (STEC) strains are primarily food-borne pathogens that may cause diarrheal outbreaks and are associated with severe complications, specifically hemolytic-uremic syndrome (HUS). We report here ge-nome sequence data for STEC O26:H11, which is associated with a cluster of cases of HUS, a rarely described syndrome in South Africa.

We carried out a retrospective survey on 152 children and adolescents with nephrocalcinosis (NC) in 22 German centers of pediatric nephrology. Etiology, clinical manifestations, growth and development, sonographic appearance of NC and renal function were analyzed. The median age at the time of diagnosis was 3.3 (range 0.1-21) years and the median duration of follow-up was 4.1 years. In 34% of children NC was associated with idiopathic hypercalciuria (IHC) and in 32% with various hereditary tubular disorders. In 9% NC was observed subsequent to prophylactic bolus administration of vitamin D in infancy. A positive family history was found in 36%. Clinical manifestations were mainly failure to thrive during the 1st year of life (46%), psychomotor/mental retardation (28%) and urinary tract infection (34%). In 14% nephrolithiasis was associated. During the follow-up the proportion of patients with the most severe degree of NC (stages 2b or 3) increased from 40% to 55% and that of hypercalciuria decreased from 79% to 52%. Body height was <2 standard deviation scores (SDS) of normal in 41% at the time of diagnosis and in 32% at the last observation; the increase in relative height was significant only for IHC. Glomerular filtration rate (GFR) and urinary concentration capacity changed only slightly with time. At the last investigation GFR was <50 ml/min/1.73 m2 in 6% and concentration capacity <800 mosmol/kg in 48% of patients. The degree of NC was negatively correlated with GFR and concentration capacity.

Abstract. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubular disorder that is frequently associated with progressive renal failure. The primary defect is related to impaired tubular reabsorption of magnesium and calcium in the thick ascending limb of Henle's loop. Mutations inPCLN-1, which encodes the renal tight junction protein paracellin-1 (claudin-16), were identified as the underlying genetic defects. Comprehensive clinical data and the results ofPCLN-1mutation analysis of 25 FHHNC families with 33 affected individuals are presented. Patients presented mainly with urinary tract infections, polyuria, and hematuria at a median age of 3.5 yr. At the time of diagnosis, the GFR was already decreased to <60 ml/min per 1.73 m2for 11 patients. Twelve patients exhibited progression to end-stage renal disease, at a median age of 14.5 yr. Treatment with magnesium salts and thiazides seemed to have no effect on the progression of the disease. Genotype analysis revealedPCLN-1mutations in all except three mutant alleles (94%). Fifteen different mutations were observed, including eight novel mutations. The accumulation of mutations affecting the first extracellular loop was striking, with 48% of all mutant alleles exhibiting a Leu151Phe exchange. Haplotype analysis strongly suggested a founder effect among patients with FHHNC who originated from Germany or eastern European countries. In 13 of 23 families, hypercalciuria and/or nephrolithiasis were observed in otherwise unaffected family members, indicating a possible role of heterozygousPCLN-1mutations in yielding hypercalciuric stone-forming conditions.

Posterior urethral valves (PUV) associated with renal dysplasia are one of the most common causes of end stage kidney disease (ESKD) in childhood. In order to identify risk factors for the progression of this condition to early renal failure, we have retrospectively analyzed the clinical course, renal function, and first postnatal renal ultrasound in a sample of 42 young male patients with PUV, who were followed at a single center. Twelve (28.6%) were diagnosed with ESKD at a median age of 11.3 years. Our comparison of PUV patients without decreased estimated glomerular filtration rate (eGFR) (group A; K/DOQI CKD stage 0-1) with PUV patients showing a decreased eGFR (group B; K/DOQI CKD stage 2-5) revealed the following significant risk factors for loss of eGFR: renal volume <3rd percentile (P < 0.001), elevated echogenicity (P = 0.001), pathologic corticomedullary differentiation (P < 0.001), >3 febrile urinary tract infections (P = 0.012), and decreased eGFR at 1 year of age (P < 0.001). Receiver operating characteristic curve analysis in the cohort confirms that patients showing a renal volume >88.2 ml/m(2) body surface area (BSA) are not at risk to develop K/DOQI CKD stage 5 (sensitivity 75%, specificity 77.3%, positive/negative predictive value 37.5/94.4%). Ultrasound promises to be a valuable tool for identifying endangered patients.

The are various opinions about the optimal therapy of endemic goiter in adolescents. From 106 patients (75 girls) suffering from endemic goiter 50 patients (group A) were treated with 300 micrograms iodine per day and 56 patients (group B) with 100 micrograms iodine plus 100 micrograms levothyroxine per day. Before therapy and after 172 days of therapy on average the thyroid volume, the thyroid hormones (TSH, T3, T4) and the lipidparameters (cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) were measured. Within the period of treatment the thyroid volume (measured by ultrasound) decreased by 11.3% in group A and by 23% in group B. The iodine deficiency was corrected completely in both groups. However, investigations in both groups proved that patients undergoing combined therapy excrete the iodine administered additionally. Analogously to studies of the intrathyreoidal iodine metabolism it can be concluded that combined therapy on the basis of the dose mentioned above does either not result in an increase in the intrathyreoidal iodine contents or in a minor increase only. Iodine treatment as well as combined treatment cause a decrease in TSH-levels and an increase in T4-levels. The changes are only significant in group B. In the total group the percentage of T3-increases was reduced from 45% to 33% during treatment. The initially elevated plasma concentration of cholesterol, LDL-cholesterol and triglycerides - compared to the control group - decreased significantly in both groups during therapy. Both groups does not differ significantly with respect to the decrease in lipids. It is to be concluded that combination therapy is preferable to iodine therapy with respect to the SD-volume reduction as well as the lipid metabolism. The primary cause of endemic goiter, i.e. the intrathyreoidal iodine deficiency, can presumably not be eliminated by means of the dose of 100 micrograms iodine combined with 100 micrograms LT4.

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An investigation was carried out in to thyroid hormones (TSH, T3, T4) and lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride) in 136 adolescents (94 femals, average age 13 years). An iodine deficiency (grade II-II) with respect to the daily urine excretion per 1,73 m2 BSA was found in 75%. With few exceptions the serum levels of TSH and T4 were in the normal range. In 36% of the patients we noticed compensatory elevated T3 levels. Correlations between thyroid hormones TSH, T4, renal iodine excretion and the volume of thyroid glands were not detectable, only T3 showed a dignificant positive correlation to the thyroid gland volume. The average values of lipids in patients were found to be higher than in normals. We consider the changed lipids as a sign of a disturbed efficacy of thyroid hormones. The regional insufficient iodine supply causes goiters and to a high degree the observed hyperchole-sterolemia, too. Our results underline the necessity of a common iodine salt prophylaxis as well as the treatment of "harmless" goiters in puberty.

Our results demonstrate that diagnostic procedures based on the detection of stx genes and/or Stx production and subsequent subtyping of the isolates using molecular methods are necessary to identify such outbreaks caused by non-O157:H7 STEC.