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Gitelman syndrome (GS) is a rare renal tubulopathy with an autosomal recessive mode of inheritance, caused by biallelic pathogenic variants in the SLC12A3 gene. The clinical features may overlap with other disorders, such as Bartter syndrome type 3, HNF1B nephropathy or even mitochondrial disease, but can be distinguished by molecular genetic analysis. Here we report on two preschool brothers, who presented with a several months' history of episodes of carpopedal spasms and muscle aches. The biochemical analyses revealed hypokalemia and hypomagnesemia without metabolic alkalosis. A 24-h urine sample demonstrated hypocalciuria. The molecular analyses showed that both patients were heterozygous for 3 (likely) pathogenic variants in SLC12A3: c.1805_1806del; p. (Tyr602Cysfs*31), c.2660+1G>A and c.2944 A>T; p. (Ile982Phe). Analysis of the parents showed that the mother was heterozygous for the c.2944 A>T p.(Ile982Phe) variant, and the father carried the other 2 variants (c.1805_1806del and c.2660+1G>A). Herein we present two children in a family from N. Macedonia with clinical manifestations and electrolyte imbalances suggestive of GS. The results of the tubulopathy next generation sequencing (NGS) panel confirmed the diagnosis. The boys are treated with a high salt diet and oral potassium and magnesium supplements. [ABSTRACT FROM AUTHOR]

Disorders of sex development (DSD) are a group of rare conditions characterized by discrepancy between chromosomal sex, gonads and external genitalia. Congenital abnormalities of the kidney and urinary tract are often associated with DSD, mostly in multiple malformation syndromes. We describe the case of an 11-year-old Caucasian boy, with right kidney hypoplasia and hypospadias. Genome-wide copy number variation (CNV) analysis revealed a unique duplication of about 550 kb on chromosome Xq27, and a 46,XX karyotype, consistent with a sex reversal phenotype. This region includes multiple genes, and, among these, SOX3 emerged as the main phenotypic driver. This is the fifth case reporting a genomic imbalance involving the SOX3 gene in a 46,XX SRY-negative male, and the first with associated renal malformations. Our data provide plausible links between SOX3 gene dosage and kidney malformations. It is noteworthy that the current and reported SOX3 gene duplications are below the detection threshold of standard karyotypes and were found only by analyzing CNVs using DNA microarrays. Therefore, all 46,XX SRY-negative males should be screened for SOX3 gene duplications with DNA microarrays. [ABSTRACT FROM AUTHOR]

Nephrogenic diabetes insipidus (NDI) is caused by the inability of renal collecting duct cells to respond to arginine vasopressin (AVP)/antidiuretic hormone (ADH). We present the case of a 7-year-old boy with a history of excretion of large amounts of dilute urine and polydipsia since infancy. The boy had several vomiting episodes with mild dehydration during the first 3 years of life. There was no evidence of headaches, dizziness or visual problems. He drinks between 2 and 3 L/day and has 24-hour diuresis of 2 liters, now. He has prepubertal appearance with appropriate weight [+0.85 standard deviation score (SDS)] and height (+0.15 SDS) for his age. His intelligence was also normal. The water deprivation test showed low urine osmolality after 8 hours of dehydration. After desmopressin administration, urine osmolality remained low. Serum osmolality was in the normal range for sex and age before and after desmopressin administration. This indicated a nephrogenic form of diabetes insipidus. Molecular analyses revealed a P286L [p.Pro(CCC)286Leu(CTC)] mutation in the AVPR2 gene, that was inherited from his mother. This patient is the first case with genetically confirmed X-linked inherited form of NDI in the Republic of Macedonia. Molecular analysis confirmed the clinical diagnosis and enabled genetic advice for this family. [ABSTRACT FROM AUTHOR]

Background: Oculocerebrorenal (Lowe) syndrome is an X-linked multisystem disease characterized by renal proximal tubulopathy, mental retardation, and congenital cataracts. We present a 19-year-old boy who was found to have low molecular weight proteinuria, hypercalciuria, mild generalized hyperaminoaciduria and intermittent microscopic hematuria at the age of 3. Methods: Standard clinical and biochemical examinations and mutational analysis of the CLNC5 and OCRL1 gene were performed for the patient. Results: The patient fulfilled diagnostic criteria for Dent disease, but lacked mutation in CLCN5. Sequencing of candidate genes revealed a mutation in his OCRL1 gene, which encodes for enzyme PIP2 5-phosphatase. The enzyme was not detected by western blot analysis, and decreased activity of the enzyme PIP2 5-phosphatase was observed in cultured skin fibroblasts. The boy had only mild mental retardation, mildly elevated muscle enzymes, but no neurological deficit or congenital cataracts, which are typical for Lowe syndrome. Conclusions: Children with Dent phenotype who lack CLCN5 mutation should be tested for OCRL1 mutation. OCRL1 mutations may present with mild clinical features and are not necessarily associated with congenital cataracts. [ABSTRACT FROM AUTHOR]

Aldosterone synthase deficiency (ASD) type II was diagnosed in a 3 week old boy with severe dehydration. Elevated plasma renin activity, low-normal aldosterone, increased levels for 18- OH corticosterone (18-OHB) and 18-OH-deoxycorticosterone were measured. Sequencing revealed a homozygous mutation for c554C>T in exon 3 (p.T185I) (CYP11B2). Hypospadias has so far not been reported in ASD. [ABSTRACT FROM AUTHOR]

Objective: There are few data in the published literature on the occurrence of subclinical post-streptococcal glomerulonephritis. In order to estimate the incidence of subclinical disease, 75 families of index cases with sporadic clinical post-streptococcal glomerulonephritis were screened for the presence of subclinical disease.Methods: Three hundred and seventeen family contacts were investigated 1-7 days after the admission of the index cases. The diagnosis of subclinical disease was based on the presence of abnormal urinalysis, transitory hypocomplementaemia and increased antistreptolysin O titre.Results: No cases of clinical/subclinical disease were detected among 147 parents. Abnormal urinalyses were found in 22.3% of sibling contacts. The incidence of nephritis among 170 siblings was 9.4% and the calculated ratio subclinical/clinical disease was 0.11. There were 16 siblings (9.4%) whose abnormal urinalyses could not be explained by appropriate tests; 11 of them had dysmorphic microhaematuria and significantly elevated antistreptolysin O titre.Conclusions: Sibling contacts have increased risk for the development of clinical/subclinical post-streptococcal glomerulonephritis compared with their parents. Sibling contacts with unexplained urinary abnormalities might have subclinical nephritis in evolution; their complement levels normalized before occurrence of nephritis in index cases. [ABSTRACT FROM AUTHOR]

The occurrence of nephrotic syndrome after an insect sting is rarely reported in the literature. A 2-year-old boy developed generalized edema 5 days after a bee sting. The laboratory investigations revealed nephrotic range proteinuria, hypoproteinemia, hypoalbuminemia and hyperlipidemia. The corticosteroid treatment induced prompt remission with resolution of edema and normalization of the laboratory findings. There was no relapse of the disease during the 13-year follow-up. Although spontaneous remission might occur, corticosteroid treatment induced prompt remission and shortened the hospital stay. [ABSTRACT FROM AUTHOR]

Describes two novel missense insulin receptor mutations found in a patient with Donohue syndrome. Exhibition of distinct functional defects that act in a synergistic manner, resulting in extreme form of insulin resistance; Effects of the mutations on insulin receptor function; Decreased insulin binding; Defective tyrosine kinase activity.

Congenital anomalies of the kidney and urinary tract- CAKUT are common childhood pathology accounting for 20-30% of perinatally detected congenital anomalies. CAKUT significance implies to the risk they represent to kidney function deterioration and end stage renal disease development. The aim of this study is to analyze the clinical course and outcome in patients with early diagnosed CAKUT. The study design is retrospective observational study. 100 patients with early diagnosed CAKUT at University children hospital, Skopje, were enrolled in the study. The results from this study represent the clinical course and outcome in the study group. Urinary tract infections were seen in 30% of patients enrolled in this study, they were predominantly girls (65%), mostly diagnosed with posterior urethral valve, VUR and UPJO. Surgical treatment was needed in 28% of patients, and chronic renal failure was diagnosed in 4% of the total number of patients in this study. This study strikes to contribute to early diagnosed CAKUT understanding as well as establishing a protocol for early detection and adequate treatment initiation to prevent renal function deterioration. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding Lesch-Nyhan disease (LND), a purine metabolism inborn defect resulting from hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency.

Focuses on imaging of children with culture-negative acute pyelonephritis. Urine cultures responsible for acute pyelonephritis; Overview of the desirability of computed scans of children with urinary tract infection; Information on the processing of urine samples of such children.