Two Brothers from Macedonia with Gitelman Syndrome.

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.

Renal dysplasia in Bardet-Biedl syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a multisystem genetic disorder characterized with central obesity, pigmentary retinopathy, polydactyly, mental retardation, and hypogenitalism. Renal abnormalities have been recognized as a cardinal feature of the disease with serious prognostic implication. The aim of this study was to analyze the renal status in children with BBS and to implement appropriate interventions in those with progressive course Patients and methods: The diagnosis of BBS was established on the basis of criteria proposed by Beales et al. (J Med Genet 1999). Imaging of the kidneys and urinary tract was performed with ultrasound study, Tc99(m)DMSA scan and a cystographic study. Twenty four hour urine collections were obtained for estimation of proteinuria and creatinine clearance. Blood pressure was monitored at clinical visits or as 24-hour ambulatory monitoring. RESULTS: There were 4 children (2 males, 2 females). All four children displayed abnormal kidney ultrasound and Tc99(m)DMSA scan resembling dysplastic kidney(s). Two of them had overt proteinuria (glomerulo-tubular pattern). Three children had normal blood pressure and glomerular filtration rate (GFR): 107, 145 and 95 ml/min/1.73m(2), and the fourth had hypertension and progressive worsening of the GFR at 65 ml/min/1.73m(2). CONCLUSION: Children with BBS should undergo imaging studies of the kidneys and urinary tract at initial work up; in those with renal dysplasia proteinuria, GFR and blood pressure should be regularly monitored to slow down progression to terminal renal failure.

X-Linked Recessive form of Nephrogenic Diabetes Insipidus in a 7-Year-Old Boy.

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.