Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families.

BACKGROUND: Autosomal recessive distal renal tubular acidosis (dRTA) is a rare disease characterized by a hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria, hypocitraturia, nephrocalcinosis, and conserved glomerular filtration rate. In some cases, neurosensorial deafness is associated. dRTA is developed during the first months of life and the main manifestations are failure to thrive, vomiting, dehydration, and anorexia. METHODS: Nine unrelated families were studied: seven children, a teenager, and an adult with dRTA. Hearing was preserved in four children. Coding regions of the genes responsible for recessive dRTA were analysed by Sanger sequencing. RESULTS: Molecular defects were found in the genes ATP6V1B1 and ATP6V0A4. We identified three homozygous variants in ATP6V1B: a frameshift mutation (p.Ile386Hisfs*56), a nucleotide substitution in exon 10 (p.Pro346Arg), and a new splicing mutation in intron 5. Three patients were homozygous for one novel (p.Arg743Trp) and one known (p.Asp411Tyr) missense mutations in the ATP6V0A4 gene. Three patients were compound heterozygous: one proband displayed two novel mutations, the frameshift mutation p.Val52Metfs*25, and a large deletion of exons 18-21; two probands showed the missense mutation p.Asp411Tyr and as a second mutation, p.Arg194Ter and c.1691+2dup, respectively. CONCLUSION: ATP6V0A4 and ATP6V1B1 genes were involved in recessive dRTA of Mexican families. All ATP6V1B1 mutations detected were homozygous and all patients developed sensorineural hearing loss (SNHL) early in infancy. ATP6V0A4 mutations were found in one infant and three children without SNHL, and in one teenager and one adult with SNHL confirming the phenotypic variability in this trait. The mutation p.Asp411Tyr detected in four Mexican families was due to a founder effect. Screening of these mutations could provide a rapid and valuable tool for diagnosis of dRTA in this population.

Redes neurais artificiais aplicadas ao processo de coagulação / Artificial neural networks applied to the coagulation process

A coagulação é uma etapa de tratamento da água, e para tal são realizados ensaios de teste de jarro que permitem determinar a dose necessária dos agentes coagulante e químico de ajuste de pH no processo de coagulação. Contudo, esses ensaios demoram a ser executados, não respondendo em tempo real às mudanças da qualidade da água bruta. Para superar tal limitação, redes neurais artificiais multicamadas foram construídas (e seus pesos sinápticos ajustados), validadas e testadas para predizer a dosagem do hidróxido de sódio e do sulfato de alumínio - utilizados como agentes químico de ajuste de pH e coagulante, respectivamente. Os resultados dos modelos obtidos são compatíveis com os dados experimentais tendo em vista que as incertezas das estimativas estão na mesma ordem de grandeza das faixas indicadas pelos ensaios realizados de testes de jarro ao longo de quase seis anos.

Coagulation is a stage in water treatment and, for this, jar tests are performed, which allows determining the optimal coagulant and alkalizer doses in coagulation process. However, these tests are time-consuming and do not enable real-time responses to changes in raw water quality. To overcome these limitations, artificial multilayer perceptron neural networks were built, trained, validated and tested to predict the aluminum and sodium hydroxide doses - used as coagulant and alkalizer, respectively. The results of these models are encouraging to consider that the estimated uncertainties have the same order of the variation limits magnitude indicated by the jar tests for almost a six-year period.

Serum markers of low-turnover bone disease in Mexican children with chronic kidney disease undergoing dialysis.

BACKGROUND: The frequency of low-turnover bone disease (LTBD) in patients with chronic kidney disease (CKD) has increased in past years. This change is important because LTBD is associated with bone pain, growth delay, and higher risk for bone fractures and extraosseous calcifications. LTBD is a histological diagnosis. However, serum markers such as parathyroid hormone (PTH) and calcium levels offer a noninvasive alternative for diagnosing these patients. OBJECTIVE: To describe the prevalence of LTBD in pediatric patients with renal failure undergoing some form of renal replacement therapy, using serum calcium and intact PTH levels as serum markers. METHODS: In this cross-sectional study, 41 children with CKD undergoing dialysis treatment (31 on continuous ambulatory peritoneal dialysis and 10 on hemodialysis) were included. There were no inclusion restrictions with respect to gender, cause of CKD, or dialysis modality. The children were studied as outpatients. The demographic data, CKD course, time on dialysis, phosphate-binding agents, and calcitriol prescription were registered, as well as weight, height, Z-score for height, linear growth rate, and Z-score for body mass index. Serum calcium, phosphorus, aluminum, PTH, alkaline phosphatase, osteocalcin, glucose, creatinine, urea, cholesterol, and triglycerides were measured. RESULTS: There were 20 (48.8%) children with both PTH < 150 pg/mL and corrected total calcium >10 mg/dL who were classified as having LTBD[(+)]; the remaining 21 (51.2%) children were classified as having no LTBD[(-)]. The LTBD(+) patients were younger (11.2 +/- 2.7 vs 13.2 +/- 2.4 years, p < 0.01) but they had no differences regarding Z-scores for height. Linear growth in 6 months was less than expected in both groups (-0.15 +/- 0.23 cm/month), but the difference between expected and observed growth was higher in the LTBD(+) group (-0.24 +/- 0.14 vs -0.07 +/- 0.28 cm/mo, p < 0.03). LTBD(+) patients also had lower serum creatinine (8.69 +/- 2.75 vs 11.19 +/- 3.17 mg/dL, p < 0.01), higher serum aluminum levels [median (range) 38.4 (9 - 106) vs 28.1 (9 - 62) microLg/L, p < 0.05], and lower systolic blood pressure (112.0 +/- 10.3 vs 125.0 +/-1 2.9 mmHg, p < 0.015) and diastolic blood pressure (76.0 +/- 9.7 vs 84.5 +/- 8.2 mmHg, p < 0.017). A significant correlation was found between PTH and alkaline phosphatase (r = 0.68, p < 0.001), but not between PTH and aluminum. CONCLUSION: The LTBD(+) biochemical profile was found in 48.8% of the children and was associated with impaired linear growth. Aluminum contamination, evidenced by higher serum aluminum levels, may have had a pathogenic role in these disorders. Higher systolic and diastolic blood pressure levels may be related to higher serum PTH levels.