Renal transplantation in 4 patients with methylmalonic aciduria: A cell therapy for metabolic disease

被引：37

作者：

Brassier, A. ^{[1
]}

Boyer, O. ^{[2
]}

Valayannopoulos, V. ^{[1
]}

Ottolenghi, C. ^{[3
,4
]}

Krug, P. ^{[2
]}

Cosson, M. A. ^{[1
]}

Touati, G. ^{[1
]}

Amoux, J. B. ^{[1
]}

Barbier, V. ^{[1
]}

Bahi-Buisson, N. ^{[5
]}

Desguerre, I. ^{[5
]}

Charbit, M. ^{[2
]}

Benoist, J. F. ^{[6
]}

Dupic, L. ^{[7
]}

Aigrain, Y. ^{[8
]}

Blanc, T. ^{[8
]}

Salomon, R. ^{[2
]}

Rabier, D. ^{[3
,4
]}

Guest, G. ^{[2
]}

de Lonlay, P. ^{[1
]}

Niaudet, P. ^{[2
]}

机构：

[1] Univ Paris 05, Hop Necker Enfants Malad, Ctr Reference Malad Hereditaires Metab Enfant & A, Inst Imagine, Paris, France

[2] Univ Paris 05, Hop Necker Enfants Malad,Sorbonne Paris Cite, Ctr Reference Malad Renales Hereditaires Metab &, Serv Nephrol Pediat,Inserm,U983,Inst Imagine, Paris, France

[3] Univ Paris 05, Hop Necker Enfants Malad, Lab Biochim Metabol, Paris, France

[4] Univ Paris 05, Hop Necker Enfants Malad, INSERM, U747, Paris, France

[5] Univ Paris 05, Hop Necker Enfants Malad, Ctr Reference Malad Neuromusculaires, Unite Neuropediat, Paris, France

[6] Hop Robert Debre, Lab Biochim Hormonol, F-75019 Paris, France

[7] Univ Paris 05, Hop Necker Enfants Malad, Paris, France

[8] Univ Paris 05, Hop Necker Enfants Malad, Serv Chirurg Viscerale Pediat, Paris, France

来源：

MOLECULAR GENETICS AND METABOLISM | 2013年 / 110卷 / 1-2期

关键词：

Methylmalonic acidemia; Chronic renal disease; Renal transplantation; MULTIPLE OXPHOS DEFICIENCY; LIVER-TRANSPLANTATION; COA MUTASE; ACIDEMIA; KIDNEY; MANAGEMENT; FAILURE;

D O I：

10.1016/j.ymgme.2013.05.001

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Introduction: Patients with methylmalonic acidemia (MMA) may develop many complications despite medical treatment, in particular, severe central nervous system damage and chronic kidney disease (CKD). A kidney transplant may partially correct the metabolic dysfunctions. Liver, kidney and combined liver-kidney transplantations have been advocated but no guidelines are available to identify the most suitable organ to transplant. Patients and methods: Four patients with MMA (mut degrees phenotype) received a kidney graft because of repeated metabolic decompensations, with progression to CKD in 3 patients (end-stage kidney disease in two patients and CKD stage III in one patient with an estimated glomerular filtration rate [eGFR] of 40 ml/min/1.73 m(2)) but normal renal function in one (eGFR of 93 ml/min/1.73 m(2)) before transplantation. Results: The medium age at transplantation was 7.9 y (5-10.2) and the median follow-up was 2.8 years (1.8-4.6). Renal transplantation improved the relevant metabolic parameters in 4/4 patients and renal function in the patients with CKD. Plasma and urinary MMA levels immediately decreased and remained normal or subnormal (mean values of plasma MMA before transplantation 1530 mu mol/L versus 240 mu mol/L after transplantation, and mean values of urine MMA before transplantation 4700 mmol/mol creatinine versus 2300 mmol/mol creatinine after transplantation). No further acute metabolic decompensation was observed and protein-intake was increased from 0.60 to 0.83 g/Kg/day. One patient transplanted at age 9.7 years developed a hepatoblastoma at age 11 years with subsequent neurological complications and eventually died. The three other patients are alive. Two of them remained neurologically stable. The 3rd patient who displayed choreoathetosis transiently improved his neurological condition immediately after transplantation and then remained stable. Conclusion: Kidney transplantation represents an interesting alternative therapeutic option in methylmalonic aciduria, for renal complications but also as a "cellular therapy" that may significantly reduce metabolic decompensations and hospitalizations. However, further neurological impairment remains possible. (C) 2013 Published by Elsevier Inc.

引用

页码：106 / 110

页数：5

共 23 条

[1] EXPRESSION OF RECOMBINANT HUMAN METHYLMALONYL-COA MUTASE - IN PRIMARY MUT FIBROBLASTS AND SACCHAROMYCES-CEREVISIAE [J].