Kidney transplantation in a girl with methylmalonic acidemia and end stage renal failure

Abstract

Methylmalonic acidemia (MMA) is an inborn error of organic acid metabolism that occurs in infancy with hypotonia, vomiting, dehydration, lethargy and failure to thrive and is biochemically characterized by metabolic ketoacidosis, hyperammonemia and sometimes hyperglycinemia. It results from deficiency of methylmalonyl-CoA mutase activity due to a defect in the mutase apoenzyme or to deficient function of one of the enzymes required for metabolism of its cofactor vitamin B12. Tubulointerstitial nephritis with progressive impairment of renal function is one of the most frequent long-term complications. We describe a case of a 17-year-old girl with methylmalonic acidemia unresponsive to vitamin B12 therapy. The clinical symptoms appeared at 4 months of life. She progressed into end stage renal disease and in January 1996 she started on hemodialytic treatment. In November 1996 we performed a kidney transplant. At present, urinary excretion of methylmalonic acid is normal and the renal function of the transplanted kidney is normal without any rejection episodes. We think that a kidney transplant could be a good therapeutic choice for the metabolic alterations in MMA with end stage renal disease. Indeed it would seem that the small methylmalonyl-CoA mutase activity present in the transplanted kidney could be sufficient to ensure normal metabolism of organic acids. Otherwise, the therapeutic goal can be achieved with a protein-restricted diet.

Renal transplant in methylmalonic acidemia: could it be the best option?

“…We had previously reported on the case 4 years after transplant [20]. Presently, at 10-year follow-up, her renal function and her clinical state is satisfactory.…”

“…Examining the reported outcomes, it is immediately apparent that renal transplant, either alone [20,40,41] or in combination [32,38,39], attains better results: all patients are alive, and in all but one the metabolic status has improved. On the contrary, of the ten solo liver transplants [18,[30][31][32][33][34][35][36][37], only two are reported uneventful, whereas two have suffered from severe metabolic disorders, one has manifested progressive neurological deficit after transplantation, one is alive with neurological deficits, two died in the postoperative period due to sepsis, and of the remaining two cases, there are no outcome data available.…”

“…At present, when medical treatment is ineffective, even in the absence of end-stage renal disease (ESRD), extracorporeal hemodialysis offers satisfactory control of metabolic disequilibria [5] but at a cost in terms of quality of life [5,14]. Therefore, in case of medical treatment failure, before renal failure ensues and particularly when there is progressive neurological deficit, some authors suggest liver transplant [18,[30][31][32][33][34][35][36][37]; however, when MMA has progressed to ESRD, combined transplant of liver and kidney [32,38,39] or kidney only [20,40,41] is usually undertaken ( Table 2).…”

Peritoneal dialysis for chronic renal failure in a patient with methylmalonic acidaemia

“…Renal function may improve with optimised dietary management [9]. Renal transplantation has been undertaken in a number of patients [10], although concerns have been expressed about recurrent disease in the transplanted kidney. Transplantation is often timed to avoid the need for dialysis; in other cases, HD has been used [4].…”

Correction of Methylmalonic AciduriaIn VivoUsing a Codon-Optimized Lentiviral Vector

“…This is also suggested by Kaplan et al (2006) and Kasahara et al (2006), who both challenge the rationale of liver transplantation. In fact, a few reports have also suggested that the benefit of either renal or combined transplantation (van't Hoff et al, 1999;Chakrapani et al, 2002;Nyhan et al, 2002;Hsui et al, 2003;Kaplan et al, 2006;Kasahara et al, 2006) is greater than that of liver transplantation alone (Van Calcar et al, 1998;Lubrano et al, 2001;Coman et al, 2006).…”