Application of molecular methods of genetic counseling in inherited forms of renal tubular acidosis for preventive strategy

Renal tubular acidosis [RTA] results from failure of the kidney to acidify the urine resulting in a state of hyperchloraemic metabolic acidosis with a normal anion gap. Three main clinical types of RTA are now recognized [proximal, distal and hyperkalemic] but the number of possible causes is large. Inherited forms of distal RTA have three variants: autosomal dominant and autosomal recessive with or without deafness, while the inherited forms of proximal RTA include many variants as autosomal recessive proximal RTAt cystinosis, Fanconi-Bickel syndrome [FBS] and Wilson's disease. Thus, we conducted a prospective study to screen all the documented cases of inherited RTA in pediatric nephrology outpatient clinic in MUCH for relevant gene mutation. This study was carried out in the period from November 2009 to February 2012. The study comprised 17 Egyptian families having documented cases of inherited RTA. We found three families compatible with the clinical diagnosis of FBS, two families compatible with the clinical diagnosis of cystinosis and 12 families of dRTA. All patients were subjected to a thorough history, full clinical examination and laboratory investigations. Pedigree construction was done for each family. Radiological investigations were done for some cases including plain x-ray for racketic findings, abdominal ultrasound and echocardiography done for those with clinical findings coping with congenital or acquired heart diseases. Liver biopsy was done for those with hepatomegaly. Molecular workup was done in the form of DNA extraction, agarose gel electrophoresis, polymerase chain reaction of the extracted DNA and sequencing for the specific gene according to each disease. We found two new mutations in GLUT2 gene and an old missense mutation [re-enumerated] in three families of FBS. We found a novel truncating mutation in CTNS gene associated with a severe clinical course and double heterozygosity for two known mutations in the other family. Two novel mutations were detected in two out of 12 families of dRTA in ATP6VOA4 gene. We concluded that although these diseases are not rare in the Egyptian population, evolving new mutations could add some allelic variants. Moreover, studying phenotype-genotype pattern of different mutations is crucial for linkage analysis

Hormonal, sonographic, and body composition changes in Egyptian adolescent girls with hyperandrgenie manifestation

This study was conducted to assess the prevalence of hyperandrogenic disorders especially polycystic ovary syndrome [PCOS] in a random sample of adolescent girls in our locality, as well as to identify the clinical; hormonal, ultrasonic, and body composition characteristics associated with such disorders. Two hundred school girls [15-18 years old] were selected by multi-stage random sampling from different secondary schools, and screened for hyperandrogenic disorders by a validated questionnaire. Thorough history taking, physical and gynecologic examination, complete hormonal, pelvi-abdominal pulse inversion harmonic imaging [PlHl], and body composition assessment by bioelectrical impedance [BIA] were done for students presenting with menstrual dysfunction and/or clinical hyperandrogenism and 8 controls from the 4th to the 7th day of the menstrual cycle. Twenty-five out of the 200 students were thoroughly evaluated. Eighteen adolescents of the examined students [72%] were finally diagnosed as PCOS, 5 [20%] as idiopathic hyperandrogenism and 2 [8%] s non-classic congenital adrenal hyperplasia [CAH]. Despite normal weight percentiles and body mass index [BMI] for age and sex in 83.3% and 88.9% of students with PCOS respectively, fat mass, trunk fat percentage, trunk fat mass, and trunk free fat were significantly higher in PCOS patients compared to controls. PCOS was the most common hyperandrogenic disorder in this study. Combined menstrual dysfunction and clinical hyperandrogenism had adequate sensitivity and high specificity in the prediction of PCOS. PIHI is an adequately sensitive preferential diagnostic tool of PCOS in virgin adolescents who may have central adiposity. Body composition assessment by BIA in PCOS is valuable in detecting central adiposity which could be correlated to parameters of insulin resistance