Hereditary Tubular Disorders Research Articles

Molecular Diagnosis of Primary Hyperoxaluria Type 1 and Distal Renal Tubular Acidosis in Moroccan Patients With Nephrolithiasis and/or Nephrocalcinosis.

Nephrolithiasis (NL) and urolithiasis (UL) are usual reasons for hospitalization and presentation in pediatric outpatient departments and their incidence continues to rise worldwide. In Morocco, a previous epidemiological study done in the Fez region between January 2003 and November 2013 reported a prevalence of 0.83% of childhood UL. In two studies, heritability accounted for almost half of all NL or nephrocalcinosis (NC) prevalence. Genetic factors must be considered in the etiological diagnosis of urinary lithiasis in Morocco since the frequency of consanguineous marriages is high. Hereditary tubular disorders, especially distal renal tubular acidosis (dRTA) and Dent disease, and metabolic disorders like idiopathic hypercalciuria and hyperoxaluria are the most common causes of medullary NC. Primary hyperoxaluria type 1 (PH1), which can generate an early onset of NC, and often chronic kidney disease (CKD) should always be considered and thoroughly diagnosed. The aim of this work was to establish a molecular diagnosis of PH1 and dRTA and, thus, to predict and explain the disease phenotype in a cohort of 44 Moroccan patients with NL and/or NC by analyzing the AGXT and ATP6V1B1 genes that cause NL and/or NC when mutated. Disease phenotype was molecularly explained and solved in six of 44 individuals with NL and/or NC (13.6%). In the pediatric subgroup of individuals, a causative mutation in 16.2% was identified, whereas in the adult cohort no pathogenic mutation was detected. In our patients, PH1 was objectified in 67% of cases followed by dRTA in 33% of cases. We suggest that prompt detection and prophylactic treatment of UL are necessary to limit the risk of everlasting renal damage and thus prevent or delay the progression to CKD.

Bartter Syndrome: Perspectives of a Pediatric Nephrologist.

Bartter syndrome (BS) is one of the most well-known hereditary tubular disorders, characterized by hypokalemic, hypochloremic metabolic alkalosis, and polyuria/polydipsia. This disease usually presents before or during infancy, and adult nephrologists often inherit the patients from pediatric nephrologists since this is a life-long condition. Here, a few case scenarios will be presented to recount how they first got diagnosed and how their clinical courses were during childhood until adulthood, in addition to a brief review of the disease and its treatment.

Néphrocalcinose de l’enfant

Nephrocalcinosis is defined by calcium phosphate or calcium oxalate deposits in the kidney parenchyma, particularly in tubular epithelial cells and interstitial tissue. It should be differentiated from urolithiasis where calcium salts deposits are located in the kidney and urinary tract. The epidemiology of nephrocalcinosis in children is unknown but the condition is not so rare, with an increased incidence in preterm infants. Often detected as an incidental finding, nephrocalcinosis may be classified according to the radiological type: medullary, cortical or diffuse. Nephrocalcinosis in children can be caused by a variety of etiology. The most common causes concern medullary nephrocalcinosis and include hereditary tubular disorders, in particular distal renal tubular acidosis and Dent disease, metabolic disorders such as idiopathic hypercalciuria and hyperoxaluria, and iatrogenic causes such as vitamin D intoxication. In the newborn, the main cause is hypercalciuria of the premature baby, whose multifactorial origin is largely iatrogenic. Primary hyperoxaluria which can lead to early onset nephrocalcinosis and usually to chronic kidney disease should always be considered and further investigated. In order to provide a specific diagnosis, it is essential to take into account the family history, the clinical context and complete laboratory data. Early initiation of an appropriate etiological treatment is recommended and may prevent or delay the progression to chronic kidney disease in some cases.

XANTHOGRANULOMATOUS PYELONEPHRITIS IN A CHILD: A RARE ENTITY

Xanthogranulomatous Pyelonephritis is chronic pyelonephritis uncommonly described in adults and rarely in children. It is characterised by replacement of renal parenchymal tissue by lipomatous cells making it non-functional and may be mistaken for pyonephrosis, cystic or solid tumor, and most commonly wilms tumour. It often presents as abdominal mass in children and more commonly involves left kidney. Imaging by CT scan is characteristic and histology is diagnostic. We are reporting a case in child who presented with prolonged febrile illness and documented urinary tract infection with nephrolithiasis without any abdominal lump and received antibiotics for multiple times without any improvement. USG was suggestive of pyonephrosis and multiple abscesses. However, CT scan done subsequently diagnosed as xanthogranulomatous pyelonephritis of right kidney which was confirmed on histology. After documenting no function in affected kidney with other being normal, unilateral nephrectomy was done resulting in rapid symptomatic improvement. Results for genetic analysis for suspected hereditary tubular disorders are pending.

Abordagem da glicosúria renal na criança: a propósito de um caso clínico

Introduction : The accidental finding of glycosuria should lead to the exclusion of diabetes mellitus. In the absence of hyperglycemia, glycosuria is probably of renal origin. It can be isolated, as in familiar renal glycosuria, or it can be part of a hereditary tubular disorder such as Fanconi -Bickel syndrome or associated with an acquired tubular dysfunction. The renal and tubular function should be investigated. Case report : The authors describe the case of a previously healthy five -year old child with persistent glycosuria of renal cause. The investigation showed the coexistence of elevated renal excretion of glycine. Discussion : Familiar renal glycosuria and hyperglycinuria are caused by genetic defects in different renal tubular membrane transporters. The rare association of glycosuria and glycinuria was only described in one family in the 1960’s.The authors discuss the possible pathophysiologic mechanisms of this association and the importance of studying other tubulopathies in a child with glycosuria as it has prognostic and clinical management implications.

Gitelman's Syondrome: a Hereditary Disorder Characterized by Hypokalemia and Hypomagnesaemia

Gitelman’s syndrome is a type of hereditary tubular disorder, which is caused by inactive mutations in the gene, which encodes thiazide sensitive sodium chloride cotransporter (SLC12A3) in the distal convoluted tubule. Biochemical characteristic is comparable to effect of thiazide diuretics: hypokalemia, hypomagnesaemia, hypocalciuria, hypokalemic alkalosis and blood pressure is normal or lower. Gitelman’s syndrome is typically diagnosed accidentally (hypokalemia) in adolescents or adults and the course is benign. If present, the most prominent symptoms are muscular fatigue or occasional tetany. Treatment includes magnesium and potassium salts and potassium saving diuretics. We report here a case of an adult patient with Gitelman’s syndrome. The patient was a bearer of three heterozygote mutations in the gene, which encodes thiazide sensitive sodium chloride cotransporter (SLC12A3) in the distal convoluted tubule.

A woman with red eyes and hypokalemia: A case of acquired Gitelman syndrome

Gitelman syndrome is a rare hereditary disorder of the thiazide-sensitive NaCl transporter in the distal renal tubular cells, but mimicking of such hereditary tubular disorders has been described in different autoimmune diseases (Sjögren syndrome, SLE, ...). A 62-year-old woman with painful red eyes and sicca syndrome presented at the ophthalmological department. The diagnostic evaluation identified a Sjögren syndrome with early endophthalmitis as the reason for the red eyes. Results of laboratory examination indicated severe hypokalemia, metabolic alkalosis and hypomagnesemia, although this had not been seen years earlier. Together with the urine analysis, a rare case of an acquired Gitelman syndrome was diagnosed. Substitution with potassium and magnesium improved the initial symptoms of weakness, but renal electrolyte wasting persisted even after treatment of Sjögren syndrome. In patients with autoimmune disease, laboratory analysis of serum electrolytes should be performed because different acquired tubular disorders can lead to severe hypokalemia.

Nephrocalcinosis in children: a retrospective survey. Members of the Arbeitsgemeinschaft für pädiatrische Nephrologie.

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.