RESUMO
BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder caused by impaired distal mechanisms of urinary acidification. Most cases are secondary to pathogenic variants in ATP6V0A4, ATP6V1B1, and SLC4A1 genes, which encode transporters regulating acid-base balance in the collecting duct. METHODS: Retrospective study of molecular and clinical data from diagnosis and long-term follow-up (10, 20, and 40±10 years) of 16 patients with primary dRTA diagnosed in childhood. RESULTS: Molecular analyses revealed nine patients had ATP6V0A4 pathogenic variants, five in ATP6V1B1, and two in SLC4A1. A novel intragenic deletion and a common ATP6V0A4 gene variant (c.1691 + 2dupT) in ATP6V0A4 occurred in two-thirds of these patients, suggesting a founder effect. Median age at diagnosis was 3.25 months (IQR 1, 13.5), which was higher in the SLC4A1 group. Median SDS height at diagnosis was -1.02 (IQR -1.79, 0.14). Delayed clinical diagnosis was significantly related to growth failure (P = 0.01). Median SDS height at 20 years follow-up was -1.23 (IQR -1.71, -0.48), and did not significantly improve from diagnosis (P = 0.76). Kidney function declined over time: at last follow-up, 43% had moderate to severe chronic kidney disease (CKD). Adequate metabolic control was not related to CKD development. Incidence of sensorineural hearing loss (SNHL) was high in ATP6V1B1 patients, though not universal. Patients harboring ATP6V0A4 variants also developed SNHL at a high rate (80%) over time. CONCLUSIONS: Patients with dRTA can develop moderate to severe CKD over time with a high frequency despite adequate metabolic control. Early diagnosis ameliorates long-term height prognosis.
Assuntos
Acidose Tubular Renal , Perda Auditiva Neurossensorial , Insuficiência Renal Crônica , ATPases Vacuolares Próton-Translocadoras , Acidose Tubular Renal/diagnóstico , Acidose Tubular Renal/genética , Proteína 1 de Troca de Ânion do Eritrócito/genética , Humanos , Mutação , Estudos Retrospectivos , ATPases Vacuolares Próton-Translocadoras/genéticaAssuntos
Alopecia/genética , Dermatite Esfoliativa/genética , Nefropatias/genética , Túbulos Renais/fisiopatologia , Cloreto de Sódio na Dieta/metabolismo , Alopecia/sangue , Alopecia/urina , Substituição de Aminoácidos , Criança , Consanguinidade , Dermatite Esfoliativa/sangue , Dermatite Esfoliativa/complicações , Dermatite Esfoliativa/urina , Receptores ErbB/genética , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/sangue , Nefropatias/fisiopatologia , Nefropatias/urina , Túbulos Renais/metabolismo , Mutação de Sentido Incorreto , Eliminação Renal/genética , Eliminação Renal/fisiologia , Roma (Grupo Étnico)/genéticaRESUMO
La internación de un niño en un centro de tratamiento intensivo es un evento estresante y puede ser generador de enfermedad secundaria en el niño y su familia. La familia y el equipo de salud utilizan diferentes mecanismos para afrontar esta situación, muchas veces generadoras de mayores dificultades y conflictos. Con el objetivo de acompañar a los padres en esta situación, diseñamos un trabajo pionero en nuestro medio con reuniones semanales con los familiares de niños internados en un CTI privado y representantes del equipo de salud. Se presentan los resultados de la experiencia. Se concluye que la experiencia es muy positiva y podría extenderse a otros centros asistenciales.