RESUMEN
BACKGROUND: Distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene encoding the erythroid and kidney isoforms of anion exchanger 1 (AE1 or band 3) has a high prevalence in some tropical countries, particularly Thailand, Malaysia, the Philippines and Papua New Guinea (PNG). Here the disease is almost invariably recessive and can result from either homozygous or compound heterozygous SLC4A1 mutations. METHODS: We have collected and reviewed our own and published data on tropical dRTA to provide a comprehensive series of clinical and epidemiological studies in 78 patients. RESULTS: Eight responsible SLC4A1 mutations have been described so far, four of them affecting multiple unrelated families. With the exception of the mutation causing South-East Asian ovalocytosis (SAO), none of these mutations has been reported outside the tropics, where dRTA caused by SLC4A1 mutations is much rarer and almost always dominant, resulting from mutations that are quite different from those found in the tropics. SLC4A1 mutations, including those causing dRTA, may cause morphological red cell changes, often with excess haemolysis. In dRTA, these red cell changes are usually clinically recessive and not present in heterozygotes. The high tropical prevalence of dRTA caused by SLC4A1 mutations is currently unexplained. CONCLUSION: A hypothesis suggesting that changes in red cell metabolism caused by these mutations might protect against malaria is put forward to explain the phenomenon, and a possible mechanism for this effect is proposed.
Asunto(s)
Acidosis Tubular Renal/genética , Proteína 1 de Intercambio de Anión de Eritrocito/genética , Mutación/genética , Acidosis Tubular Renal/epidemiología , Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Asia/epidemiología , Niño , Preescolar , Consanguinidad , Eritrocitos Anormales/metabolismo , Eritrocitos Anormales/fisiología , Femenino , Enfermedades Hematológicas/epidemiología , Enfermedades Hematológicas/genética , Heterocigoto , Homocigoto , Humanos , Lactante , Malaria/genética , Masculino , Papúa Nueva Guinea/epidemiología , Linaje , Fenotipo , Filipinas/epidemiología , Tailandia/epidemiologíaRESUMEN
OBJECTIVE: To determine the benefits and harms of therapies used to prevent or treat renal involvement in Henoch-Schönlein purpura. DESIGN: Systematic review of randomised controlled trials. SETTING: Secondary and tertiary paediatric and paediatric nephrology services. SUBJECTS: Ten trials involving 1230 children aged less than 18 years. MAIN OUTCOME MEASURES: Persistent proteinuria and/or haematuria. RESULTS: Meta-analyses of four trials showed no significant difference in the risk of persistent kidney disease at 6 months (379 children; relative risk (RR) 0.51, 95% CI 0.24 to 1.11) and 12 months (498 children; RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14-28 days at presentation of Henoch-Schönlein purpura compared with placebo or supportive treatment. In children with severe renal disease, there was no significant difference in the risk of persistent renal disease with cyclophosphamide compared with supportive treatment (one trial; 56 children; RR 1.07, 95% CI 0.65 to 1.78) and with cyclosporin compared with methylprednisolone (one trial; 19 children; RR 0.39; 95% CI 0.14 to 1.06). CONCLUSIONS: Data from randomised trials for any intervention used to improve renal outcomes in children with Henoch-Schönlein purpura are very sparse except for short-term prednisone, which has not been shown to be effective.