title: Management of methylmalonic acidaemia by combined liver-kidney transplantation.
abstract: Methylmalonic 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.
authors.affiliation: Pediatric Nephrology, Stanford University, California 94305-5208, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nagarajan
authors.forename: G M
authors.initials: GM
authors.lastname: Enns
authors.forename: M T
authors.initials: MT
authors.lastname: Millan
authors.forename: S
authors.initials: S
authors.lastname: Winter
authors.forename: M M
authors.initials: MM
authors.lastname: Sarwal
mesh_terms: D000293:Adolescent; D000592:Amino Acid Metabolism, Inborn Errors / Q000628:therapy*; D015992:Body Mass Index; D001835:Body Weight; D002648:Child; D002658:Developmental Disabilities / Q000209:etiology; D006801:Humans; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000628:therapy; D016030:Kidney Transplantation / Q000379:methods*; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000601:surgery*; D008764:Methylmalonic Acid / Q000097:blood* / Q000652:urine; D009132:Muscles / Q000473:pathology; D009393:Nephritis; D009395:Nephritis, Interstitial; D009747:Nutritional Physiological Phenomena; D006435:Renal Dialysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D008764:Methylmalonic Acid