Genetic variations of the SLC7A9 gene: allele distribution of 13 polymorphic sites in German cystinuria patients and controls.

Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. While mutations in the SLC3A1 gene cause type I cystinuria, patients with non-type I cystinuria carry mutations in the SLC7A9 gene. Both gene products form the renal amino acid transporter rBAT/b0,+AT affected in cystinuria. In the present study a total of 59 patients with different ethnic background were screened for sequence variations in SLC7A9, out of these 32 were of German origin. For determination of allele frequencies of detected polymorphisms, 58 healthy German controls were investigated. Molecular-genetic analysis was performed using single-strand conformation polymorphism analysis, restriction assays and sequencing. Allele frequencies were analyzed statistically for the detected polymorphisms. In addition to the 6 already known variants we identified 7 new polymorphisms. Statistical analyses showed a significantly different distribution of alleles between German patients and German controls in case of the polymorphisms c. 147C>T (exon 2), c.386C>T (exon 3), IVS3+22T>G, c.584C>T (exon 4), c.610T>C (exon 4), c.692C>T (exon 5), c.852C>A (exon 6) and c.872C>T (exon 6). In summary, our results show that cystinuria is a complex disease which is not only caused by mutations in SLC7A9 and SLC3A1, but also influenced by other modifying factors such as variants in SLC7A9.

[Autogenic training in children and adolescents with type 1 diabetes mellitus]. / Autogenes Training bei Kindern und Jugendlichen mit Diabetes mellitus Typ 1.

This paper discusses psychosocial influences of diabetes mellitus type 1 on children and young patients. A group of 21 patients, age 9 to 14 years with Diabetes mellitus type 1 attended a course in "Autogenic Training" for a period of 11 weeks. From the multidimensional questionnaire for children (PFK 9-14, SETZ U. RAUSCHE 1976) 15 dimensions of personality and 5 second rank factors were extracted at the beginning and at the end of training and 5 months later. Additionally HbA1-scores were assessed at the beginning and at the end at a 2 month and a 5 month-follow-up. At the beginning of the course only on one of the 15 scales a significant difference could be observed between experimental group and age related normal population. After training 5 scales and one second rank factor showed significant changes. Significant reduction was observed in: "need for aggressive forms of dominance behaviour" "feeling of submission with respects to other:", "emotional lability" and "tendency for dependence on adults". A significantly increased score was observed in the scale measuring "self confidence regarding one's own meaning, decisions and planning ability". The second rank faktor "neuroticism" was significantly reduced. Against expectations there was no reduction in HbA1 scores. At the end of training HbA1 scores even had increased significantly. But this might have been related to the high frequency of infections during this course. In subjective ratings of training evaluation most of the course members and their parents described fewer problems with attention, less test-anxiety and less aggression and nervousness. The results of this prospective pilot-study are discussed in terms of the psychodynamic influence on diabetes.

[Johanson-Blizzard syndrome]. / Johanson-Blizzard-Syndrom.

Johanson-Blizzard syndrome (JBS) is an autosomal recessively inherited disorder that is characterized by pancreatic insufficiency, a distinct appearance with hypo- or aplasia of the alae nasi and dental anomalies. We report on 3 patients with JBS who demonstrate the clinical variability of additional symptoms. In contrast to the common mental retardation in JBS we stress the outstanding intellectual abilities of one patient. It is important to realize the treatable dysfunctions in JBS. Specific therapy of e.g. pancreatic insufficiency and hypothyroidism can lead to a marked improvement of the clinical course. For the first time we discuss a possible sex influence. There is evidence that females have a better prognosis. The literature is reviewed, and aspects of differential diagnosis of JBS are considered.

[Pediatric inguinal hernia in continuous ambulatory peritoneal dialysis]. / Zur Problematik des kindlichen Leistenbruches unter CAPD.

We report on the case of an 11-year-old boy suffering from juvenile nephronophthisis who developed bilateral inguinal hernia (on the right as a recurrence of the neonatal operation) 5 days and 4 months after starting CAPD treatment. Before the peritoneal dialysis there had been no clinical signs and no history of inguinal hernia. On the basis of this we emphasise some particular features of inguinal hernia under CAPD treatment such as an increased risk of incarceration, the importance of genital and scrotal swelling as an early symptom, the value of peritoneography as a diagnostic aid, and the need for high ligation of the patent processus vaginalis together with reduced postoperative volumes of the peritoneal dialysate.

[Asymptomatic hypokalemia and hypomagnesemia with renal cation loss (Gitelman syndrome)]. / Asymptomatische Hypokaliämie und Hypomagnesiämie mit renalem Kationenverlust (Gitelman-Syndrom).

Hypokalemia with hyperkaliuresis was diagnosed in a 10 1/4-year-old boy, who presented with spontaneously disappearing abdominal pain. The diagnosis of Gitelman-Syndrome (asymptomatic chronic hypokalemia and -magnesemia) was established after detection of hypomagnesemia, renal magnesium losing but normal renin-angiotensin-aldosterone system and glomerular filtration rate. After oral supplementation of potassium hypokalemia persisted and hyperkaliuresis increased. The substitution was discontinued, the hyperkaliuresis diminished and the child remained asymptomatic during a 24 months follow-up. The substitution of potassium and magnesium can be avoided in children with Gitelman-Syndrome as long as they remain asymptomatic.

[Plasma exchange therapy in children and adolescents with systemic lupus erythematosus (SLE)]. / Plasmaaustauschtherapie bei Kindern und Jugendlichen mit Lupus Erythematodes (SLE).

Five children (11.5-17.5 years of age) with severe systemic lupus erythematosus (SLE) were treated with plasma exchange. Three children suffered from renal failure and hypertension, one adolescent girl from gastrointestinal and arthritic pains with fever, and one patient from generalized paresis. All patients had excessive serological signs of disease activity. Forty-five sessions of plasma exchange were performed without serious complications. Four children showed improvement of SLE after initiation of plasma exchange in combination with immunosuppressive therapy in two of them renal replacement therapy could be stopped. In the 2 patients with non-renal SLE-complications a dramatic rapid improvement of the symptoms was observed. One girl succumbed to severe hypertension with cerebral bleeding and fungal sepsis after pulsE therapy a few days after start of plasma exchange. Plasma exchange should be started before observation of life threatening complications of SLE. Further information is needed about indication, frequency and duration of plasma exchange in children with SLE.

Children with chronic renal failure in the Federal Republic of Germany: I. Epidemiology, modes of treatment, survival. Arbeits- gemeinschaft für Pädiatrische Nephrologie.

By a nation-wide retrospective survey in the Federal Republic of Germany, epidemiological data were obtained on children with chronic renal failure (CRF) up to the age of 16.0 years. During a 4-year period (1972-1975), an incidence of 6 new cases per year of CRF occurred when referring to a 1 million population of the same age. The incidence of preterminal CRF (serum creatinine greater than 2 mg/dl to end-stage) was 4.4 and its prevalence 6.4 per million per year. The incidence of terminal CRF, analyzed for a 6-year period from 1972 to 1977 increased only slightly with time (from 4.4 to 5.4 per million of the same age per year). The proportion of children with terminal CRF admitted yearly for renal replacement therapy increased during the observation time from 27% to 79% up to the age of 10 years and from 80% to 96% between 10 and 16 years of age. The number of patients alive with terminal CRF rose significantly from 11.9 in 1972 to 22.0 per 1 million of the same age in 1977. At the end of 1977, 46% of all pediatric patients on renal replacement therapy had a functioning graft, compared to 38% in 1972. The increasing number of renal transplantations was accompanied by shortening of the waiting period from first dialysis to grafting. The patient survival on dialysis and after transplantation rose significantly during two subsequent 4-year periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Children with chronic renal failure in the Federal Republic of Germany: II. Primary renal diseases, age and intervals from early renal failure to renal death. Arbeitsgemeinschaft für Pädiatrische Nephrologie.

In a retrospective survey, 623 children with chronic renal failure (CRF) comprising a 7-year period were registered in the Federal Republic of Germany. The primary renal disease could be classified in 91% of the patients. Pyelonephritis was the most frequent diagnosis (31%), followed by glomerulopathies (20%), renal hypoplasia or dysplasia (14%), cystic kidney disease including nephronophthisis (12%), other hereditary nephropathies (7%), and vascular nephropathies (4%). At the time of first presentation, 23% of the children with preterminal chronic renal failure were younger than 5 years, 34% 5 to 10 years and 43% 10 to 16 years old. At the time of renal death, the serum creatinine level was below 10 mg/dl in 84% of the children below 5 years, compared to 5% in the patients older than 10 years. The mean interval from the first presentation of CRF to the terminal stage was 6 months in vascular nephropathies, 19 months in cystic renal disease, 26 months in glomerular disorders, 32 months in pyelonephritis, and 36 months in hereditary nephropathies and in renal hypoplasia or dysplasia. The range of these intervals is so large, even when diagnostic subgroups are considered, that a reliable prediction of the individual course from the underlying kidney disease is not possible.

[Significance of family studies and kidney biopsies in children with renal hematuria]. / Uber die Bedeutung von Familienuntersuchungen und von Nierenbiopsien bei Kindern mit renaler Hämaturie.

In children with renal hematuria the Alport syndrome could be diagnosed more frequently, if electronmicroscopic examination of the patients renal biopsy and a positive family history were obtained. In 16 children with renal hematuria, Alport syndrome was suspected by renal biopsy, physical examination or family history. Electronmicroscopic examination of the biopsy specimens of all 16 children revealed thinning together with a thickening and lamellation of the glomerular basement membrane (GBM), considered to be characteristic for Alport syndrome. In 11 of the children nephropathy, inner ear deafness or ocular changes were identified in 31 family members. In these families genetic information on the risk for other children is possible; furthermore ineffective medications such as steroids and cytotoxic drugs can be avoided, once the diagnosis has been established. In 5 children with characteristic renal lesions family history revealed no further support of Alport syndrome. In these cases with presence of characteristic lesions of GMB without positive family history the diagnosis Alport syndrome cannot be established with certainty, further examinations are necessary.

[Echocardiographic studies in children with chronic kidney insufficiency and intermittent hemodialysis treatment]. / Echokardiographische Untersuchungen bei Kindern mit chronischer Niereninsuffizienz und intermittierender Hämodialysebehandlung.

Cardiac function was measured in 10 children (mean age 12 years) undergoing chronic intermittent hemodialysis. Blood pressure, heart rate and body weight were checked three times before and after hemodialysis. Echocardiographic studies were performed according to the references of the American society of echocardiography. 6 patients were normotensive, 4 patients hypertensive. Cardiac function was normal before and after hemodialysis in all patients. Ultrafiltration reduced body weight on average by 1.2 kg. The mean systolic blood pressure remained unchanged, the mean diastolic blood pressure declined in normotensive patients from 66 mm Hg to 53 mm Hg and in hypertensive patients from 100 to 85 mm Hg on average; the systolic leftventricular diameter (LVES) was reduced by dialysis from 2.7 to 2.3 cm, the enddiastolic leftventricular diameter (LVED) from 4.42 to 4.02. Cardiac output declined from 62.04 ml to 56.68 ml/min, whereas heart rate, shortening fraction and mean circumferential fiber-shortening-time increased. In normotensive patients LVED shortened more (4.4 to 3.86 cm) than in hypertensive children (4.44 to cardiac output 4.18 cm), but there were no significant differences. Significantly decreased only in the normotensive children. In hypertensive children the shortening fraction increased significantly (35.54 to 42.48%) in contrast to normotensive children (40.84 to 38.44%). Cardiac preload (LVES) and (LVED) and afterload (diastolic pressure) was reduced significantly after volume elimination. These changes in cardiac function suggest, that cardiac alterations found before hemodialysis are only functional and not structural.

[Children with posterior urethral valves, dilatation of both ureters and chronic kidney insufficiency. A retrospective analysis of effectiveness and risk of operative measures]. / Kinder mit posterioren Urethralklappen, Dilatation beider Harnleiter und chronischer Niereninsuffizienz. Eine retrospektive Analyse zur Effektivität und zum Risiko operativer Massnahmen.

In all 16 boys with posterior urethral obstruction, bilateral ureteral dilatation and chronic renal failure (serum creatinine above 2 mg/dl), who were seen during the last 12 years in our departments, data about time and outcome of urological therapeutic interventions (nephrectomy, relief of bladder outflow obstruction and ureter reimplantation) were analysed retrospectively. In five patients surgical treatment was performed in our hospital, the other 11 children were referred from other hospitals. Nephrectomy of a small but not functionless kidney was performed in three of four patients without proper indication. Bladder outflow obstruction was relieved too late in five patients and insufficiently in four. 36 ureter reimplantations were performed on 24 ureters in 14 patients; reimplantation was unsuccessful in 26 ureters (72%) either because of postoperative reflux (11 ureters) or because of postoperative obstruction (15 ureters). In our opinion in boys with posterior urethral valves and bilateral ureteral dilatation ureter reimplantation should be limited to patients with proven obstruction at the uretero-vesical junction.

[Fournier's gangrene in a 2-month-old infant]. / Fournier'sche Gangrän bei einem zwei Monate alten Säugling.

A two month old boy with Fournier's Gangrene of the scrotum as a result of unnecessary needle puncture of the hydrocele is being reported. The importance of appropriate diagnosis operation and drug-therapy is also described.

[Development of the treatment of chronic renal insufficiency in children in West Germany]. / Entwicklung der Behandlung chronisch niereninsuffizienter Kinder in der Bundesrepublik Deutschland.

In a 10 year period from January 1969 through December 1978, 527 children up to 16 years of age with end stage renal disease (ESRD) underwent renal dialysis in the Federal Republic of Germany and 156 renal transplantation. From the year 1969-1974 20,8% of the children with ESRD under 5 years of age were dialysed, 55.4% of the children 5-10 years of age and 72.4% of the children with ESRD in the age group 10-16 years. In contrast from the year 1974 through 1978 50% of the children with ESRD under 5 years of age could be dialysed, 84.8% of the children 5-10 years, and 88.8% of the children 10-16 years of age. According the data published by EDTA, the number of dialysis and renal transplantation in children in FRG (BRD) was lower than in other European countries. The number reported to EDTA from FRG thus far had not been accurate. The number of patients dialysed and transplanted had increased each year and since 1974, the number was comparable to France, Netherlands and Switzerland. However, the overall dialysis rate in Europe had reached a plateau since 1974. The 5 year survival rate for children with home or hospital dialysis in FRG (BRD) was 78%, which was worse than the rate reported by EDTA for home dialysis, which was 87%. However, the 5 year survival rate for renal transplantation was 74% for FRG (BRD) and 72% for EDTA (cadaveric renal transplantation), the results were quite comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemolytic uremic syndrome in 3 siblings.

Three female infants in a single family developed a hemolytic uremic syndrome (HUS) at nearly identical ages, 11 1/2, 12, and 16 months respectively, years apart from each other. The course of the disease was characterized by slow onset, gradual deterioration and prolonged anuria in 2 siblings, hypertension and fatal outcome in all cases. A genetic predisposition for this type of familial HUS is probable and should be taken into account in genetic counseling.

[A radioimmunoassay for the determination of human myoglobin: lower detection limit, precision and use in control of myoglobinuric kidney failure]. / Radioimmuntest zur Bestimmung von Humanmyoglobin: Untere Nachweisgrenze, Präzision, Verlaufskontrolle beim myoglobinurischen Nierenversagen.

The lower detection limit of a radioimmunoassay for human myoglobin was determined by two "precision from day to day" methods (90% and 3 s methods), and by two "precision in series" methods (95% confidence range and the method of Markowetz & Munz). According to Markowetz & Munz, the lower detection limit (as a measure of sensitivity) is the lowest myoglobin concentration which, in 15-fold assays, shows no binding value in common with that of the next highest concentration, and no activity value in common with that of the reference binding value. On theoretical grounds (precision in series) and from a practical standpoint (determination of the lower detection limit using one sample assay), this method is the most suitable for the determination of the lower detection limit as a measure of sensitivity. It remains to be seen whether this is a valid generalization for other methods.

[Nontraumatic rhabdomyolysis with reversible acute kidney failure following hyperosmolar diabetic coma in a child]. / Atraumatische Rhabdomyolyse mit reversiblem akutem Nierenversagen nach hyperosmolarem diabetischem Koma beim Kind.

A 9 10/12 year year old girl developed severe hyperosmolar diabetic coma, and 5 days later acute renal failure. Extremely elevated levels of myoglobin were measured in serum and urine with a radioimmunoassay kit leading to the diagnosis of atraumatic rhabdomyolysis. Intermittent hemodialysis was performed for 2 weeks. Subsequently myoglobin and creatinine values in serum returned to normal. Psychological disturbances and paresis of the lower extremities subsided 4 resp. 12 weeks after the onset of acute illness.

[Integrated treatment of children with chronic renal insufficiency]. / Integrierte Behandlung von Kindern mit chronischer Niereninsuffizienz.

Early diagnosis of chronic renal failure in childhood is difficult, since the course of CRF shows in children with congenital renal diseases unspecific symptoms. The active cooperation of the practical pediatrician with a pediatric nephrologist enables this team for prevention of complications of chronic uremia. The integration of treatment between general pediatrician and specialist also prevents long hospitalisation and makes the prevention of the child for the best mode of treatment possible, i.g. ambulant hospital dialysis, home dialysis or CAPD. Pediatric dialysis should be performed in one of the established 14 pediatric dialysis centres in our country, because psychological, somatic and technical problems in children differ from those in adults. In dialysed children the general pediatrician should be further involved in treatment and may contribute worthy help in medical (control of drug compliance, hypertension) and psychosocial (school, employment) care of the chronic sick children. Even after successful renal transplantation the local pediatrician should continue to be involved in patient care, in spite of more frequent check up controls at hospital.

[Kidney transplantation in childhood]. / Nierentransplantation im Kindesalter.

40 renal transplantations on children up to 15 years of age have been performed in our hospital in the years 1976 to June 1982 with one exception in 1972. We did verify the findings of previous authors that renal transplantation in children has produced good results so far (1, 5, 6). Dialysis treatment in children often evokes extreme problems for the patients, parents, and medical team. Considering this dialysis is seen as only a provisional measure, transplantation however as the final aim in the therapeutic concept of children with terminal renal insufficiency (1). Furthermore dialysis treatment for infants is justified in our opinion only if a renal transplantation ca be realized.

Survival time in cystinosis. A collaborative study.

In a retrospective study the overall survival time of 205 cystinotic patients of six countries was determined. The median survival time was 8.5 years. The median time for 'renal death' (age at death due to uraemia or age at starting renal replacement therapy) was 9.2 years. The youngest patient dying of renal death was 5.2 years. No sex difference in survival time was noticed. Furthermore no difference in survival time was noted between the different countries. The analysis of the overall survival curve indicates no clear differences between the infantile and adolescent types of cystinosis.