Management of methylmalonic acidaemia by combined liver–kidney transplantation

Journal of Inherited Metabolic Disease - Tập 28 Số 4 - Trang 517-524 - 2005
Suja Nagarajan1, Gregory M. Enns2, Maria T. Millan3, Susan Winter4, Minnie Sarwal5,6
1Pediatric Nephrology California
2Medical Genetics California
3Surgery Stanford University California
4Medical Genetics and Metabolism Valley Children's Place Madera California USA
5Pediatric Nephrology, G320, Pasteur Drive Stanford University California 94305-5208 USA
6Pediatric Nephrology, G320, Pasteur Drive Stanford University California 94305‐5208 USA

Tóm tắt

SummaryMethylmalonic acidaemia (MMA) is a rare autosomal recessive inborn error of metabolism that typically presents in infancy with recurrent episodes of metabolic acidosis, developmental delay and failure to thrive. The disease course is complicated by the development of chronic tubulointerstitial nephritis progressing to end‐stage renal disease in adolescence. We describe two adolescents with cobalamin‐nonresponsive MMA (mut0) who developed polyuria, chronic tubulointerstitial nephritis, dystonia but normal synthetic liver function. Both patients received combined liver–kidney transplantation (CLKT), preceded by a single pretransplant haemodialysis for clearance of methylmalonic acid. Post CLKT there was 95–97% reduction in serum and urine methylmalonic acid, leading to significant liberalization of dietary protein intake and a consequent increase in body mass index, muscle strength and energy. In addition, renal function normalized and clinical neurological status stabilized. We propose that CLKT be considered as a therapeutic option early in the course of cobalamin‐nonresponsive MMA. Progressive tubulointerstitial nephritis with disabling polyuria is a confounder in patient management even in the absence of end‐stage renal disease. Successful CLKT restores methylmalonyl‐CoA mutase enzyme levels in the liver and kidney, improves clearance of methylmalonic acid with resultant dietary protein liberalization, and offers excellent graft and patient outcomes with improvement in quality of life.

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Journal of Inherited Metabolic Disease

Tập 28 Số 4

517-524

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