Acute renal failure associated with bilateral enlargement of the kidneys: a rare manifestation of acute lymphoblastic leukemia (ALL).

We report a 6-year-old patient who presented with acute renal failure resolving after vigorous intravenous hydration. Renal biopsy was taken because of unexplained enlargement of both kidneys. Histological workup showed infiltration by lymphoblasts while blood counts showed a normal differential. Subsequent bone marrow aspiration revealed 34% lymphoblasts of T-lineage origin, leading to the diagnosis of T-ALL. This case underlines that malignant hematologic infiltration should be considered in patients presenting with unexplained renal failure and enlarged kidneys.

[Polyhydramnios, prematurity, dystrophy, polyuria, constipation, nephrocalcinosis and renal tumor: presentation of a classic tubulopathy]. / Polyhydramnion, Frühgeburtlichkeit, Dystrophie, Polyurie, Obstipation, Nephrokalzinose und renale Raumforderung: Präsentation einer klassischen Tubulopathie.

BACKGROUND: A diagnostic workup of a renal mass will rarely lead to the diagnosis of a tubulopathy. We would like to stress the importance of taking a detailed history and of evaluating these findings in the context of the clinical symptoms. CASE REPORT: A 3 year old boy with a renal mass, diagnosed due to urinary tract infection, was referred to exclude renal malignancy. Detailed history revealed polyuria and polydipsia in a child with preterm delivery due to polyhydramnios. These symptoms, together with poor thriving are highly suggestive of a neonatal form of Bartter syndrome. This diagnosis was substantiated by ultrasound findings of nephrocalcinosis and urolithiasis due to hypercalciuria and a renal abscess. Detection of mutations in the KCNJ1-gene confirmed the diagnosis. After unilateral nephrectomy for acute destructive nephritis and under medication with indomethacin and potassium citrate the patient is now thriving well. CONCLUSION: Renal masses suspicious of malignancy may distract from a hereditary tubulopathy. Typical clinical history and presentation with prematurity, polyhydramnios, polyuria, poor thriving and urolithiasis requires diagnostic evaluation of tubular function since routine laboratory tests and urinary dip stick may be normal. Unrecognized, neonatal Bartter syndrome may lead to severe complications including loss of kidney function.

[Sclerosing peritonitis without reduced ultrafiltration as complication of peritoneal dialysis]. / Sklerosierende Peritonitis als Komplikation bei Peritonealdialyse.

UNLABELLED: Peritoneal dialysis (PD) is the preferred method of renal replacement therapy in childhood and adolescence while waiting for a kidney transplant. As major complication, encapsulating peritoneal sclerosis (EPS), sometimes also referred to as "sclerosing peritonitis", may develop after prolonged periods of PD and lead to severe therapeutical problems. CASE REPORT: A 20-year-old patient with a history of three unsuccessful kidney transplants due to recurrence of his focal segmental glomerulosclerosis presented after 9 years of PD with acute abdominal pain and reduced bowel movements. Infectious peritonitis was excluded, ultrafiltration with 800-1 000 ml per day with low (1,36 %) glucose dialysate was not impaired. Plain abdominal X-ray, ultrasound and CT-scan illustrated characteristic peritoneal calcifications. Diagnosis of EPS was confirmed by peritoneal biopsy. The patients was switched to hemodialysis, enteral nutrition was continued, and the follow-up (now 16 months) was uncomplicated with the exception of a sterile ascites, which was twice relieved. Diagnostic and therapeutic options are discussed. CONCLUSION: In contrast to most reports, EPS may develop with unchanged ultrafiltration after prolonged periods of PD. We recommend regular functional and imaging studies in patients at risk.

Evidence for further genetic heterogeneity in nephronophthisis.

BACKGROUND: A new type of nephronophthisis (NPH) has been recently identified in a large Venezuelan kindred: adolescent nephronophthisis (NPH3) causes end-stage renal disease (ESRD) at a median age of 19 years. The responsible gene (NPHP3) maps to 3q21-q22. NPH3 shares with juvenile nephronophthisis (NPH1) the same disease manifestations such as polyuria, polydipsia, and secondary enuresis. Histopathological findings consist of tubular basement membrane changes, cysts at the corticomedullary junction, and a chronic sclerosing tubulointerstitial nephropathy. The only difference is a younger age at ESRD in NPH1 (median age of 13 years) when compared with NPH3. METHODS: In order to evaluate whether there might be a fourth locus of isolated nephronophthisis, we studied eight NPH families without extrarenal disease manifestations and without linkage to the NPH1 locus (NPHP1) on chromosome 2q12-q13. ESRD was reached at ages ranging from 7 to 33 years. Individuals were haplotyped with microsatellites covering the genetic locus of NPHP3. Infantile NPH (NPH2) was excluded in all families by the clinical history and histological findings. RESULTS: In four of the examined families haplotype analysis was compatible with linkage to the NPHP3 locus. In one of these families identity by descent was observed. In contrast, in another four families linkage was excluded for NPHP3. CONCLUSION: Four NPH-families were neither linked to NPHP1 nor to NPHP3, indicating further genetic heterogeneity within the group of nephronophthisis. The finding of further genetic heterogeneity in NPH has important implications for genetic counselling.

Homozygosity mapping of a gene locus for primary ciliary dyskinesia on chromosome 5p and identification of the heavy dynein chain DNAH5 as a candidate gene.

Reduced mucociliary clearance in primary ciliary dyskinesia (PCD) causes recurrent infections of the upper and lower respiratory tract. The disease is usually inherited as an autosomal recessive trait. To identify a gene locus for PCD, we studied a large consanguineous family of Arabic origin. Direct examination of the respiratory cilia revealed ciliary akinesia. Electron microscopic examination of cilia showed absence of the outer dynein arms. Two of four affected individuals exhibited a situs inversus, typical for Kartagener syndrome, due to randomization of the left/right body axis. A total genome scan with 340 highly polymorphic microsatellites was performed. We localized a new gene locus for PCD to a region of homozygosity by descent on chromosome 5p15-p14 with a parametric multipoint logarithm of odds ratio (LOD) score of Zmax = 3.51 flanked by markers D5S2095 and D5S502 within an interval of 20 centimorgans sex-averaged genetic distance. Applying a polymerase chain reaction-based approach, we identified a 1.5-kb partial complementary DNA of DNAH5 encoding a Chlamydomonas-related axonemal heavy dynein chain within the critical disease interval of this new PCD locus. On the basis of the Chlamydomonas model for PCD, this gene represents an excellent candidate for PCD.

Identification of a new gene locus for adolescent nephronophthisis, on chromosome 3q22 in a large Venezuelan pedigree.

Nephronophthisis, an autosomal-recessive cystic kidney disease, is the most frequent monogenic cause for renal failure in childhood. Infantile and juvenile forms of nephronophthisis are known to originate from separate gene loci. We describe here a new disease form, adolescent nephronophthisis, that is clearly distinct by clinical and genetic findings. In a large, 340-member consanguineous Venezuelan kindred, clinical symptoms and renal pathology were evaluated. Onset of terminal renal failure was compared with that in a historical sample of juvenile nephronophthisis. Onset of terminal renal failure in adolescent nephronophthisis occurred significantly later (median age 19 years, quartile borders 16.0 and 25.0 years) than in juvenile nephronophthisis (median age 13.1 years, quartile borders 11.3 and 17.3 years; Wilcoxon test P=.0069). A total-genome scan of linkage analysis was conducted and evaluated by LOD score and total-genome haplotype analyses. A gene locus for adolescent nephronophthisis was localized to a region of homozygosity by descent, on chromosome 3q22, within a critical genetic interval of 2. 4 cM between flanking markers D3S1292 and D3S1238. The maximum LOD score for D3S1273 was 5.90 (maximum recombination fraction.035). This locus is different than that identified for juvenile nephronophthisis. These findings will have implications for diagnosis and genetic counseling in hereditary chronic renal failure and provide the basis for identification of the responsible gene.

Exclusion of the candidate genes ACE and Bcl-2 for six families with nephronophthisis not linked to the NPH1 locus.

BACKGROUND: Nephronophthisis (NPH) is an autosomal recessively transmitted kidney disease, characterized by cyst formation at the cortico-medullary junction, and a sclerosing tubulointerstitial nephropathy. Juvenile nephronophthisis (NPH1) is the most common genetic cause of renal failure in children and maps to chromosome 2q12-q13. The responsible gene NPHP1 has been identified and encodes for nephrocystin. Not all families with NPH demonstrate linkage to that locus. METHODS: We studied six families with NPH without linkage to the NPH1 locus. In order to attempt identification of a new causative gene, the candidate genes ACE (angiotensin converting enzyme) and Bcl-2 (B cell leukaemia/lymphoma 2 gene) originating from mouse models, were examined. For the six families highly polymorphic microsatellites covering the whole candidate gene regions were haplotyped and linkage analysis was performed. RESULTS: Haplotype analyses of all families examined were incompatible with linkage of the disease status to ACE or Bcl-2. Linkage analysis excluded both candidate gene regions with a LOD-score of < -2. CONCLUSIONS: This study excluded the candidate genes ACE and Bcl-2 for NPH. Additional linkage studies need to be performed in order to identify further genes responsible for nephronophthisis.