Chronic renal failure in methylmalonic acidaemia (original) (raw)
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Renal transplantation in a patient with methylmalonic acidaemia
Journal of inherited metabolic disease, 1998
Renal insufficiency is frequently reported in mutase-deficient methylmalonic acidaemia. We present a case report of a patient with mut- methylmalonic acidaemia who developed chronic tubulointerstitial nephropathy during adolescence. At 24 years of age, she developed end-stage renal failure and underwent renal transplantation. Both plasma and urine methylmalonic acid levels decreased significantly with improved renal function following transplantation. Complications included cyclosporin toxicity and development of diabetes. Renal, metabolic, and clinical status remained improved at 3 years after the kidney transplant.
Long-term outcome in methylmalonic aciduria: a series of 30 French patients
2009
To better delineate the natural history of patients with methylmalonic aciduria (MMA).Thirty patients with vitamin-B12-unresponsive MMA (25 aged 1.5 to 22.0 years (y) at the end of the study and 5 who died during a metabolic crisis) were managed following standardized guidelines and studied retrospectively. The median follow-up was 8.3 y (range: 1.4–19.5). Patients were investigated with neuropsychological testing, brain MRIs, inulin clearances, biochemical and genetic studies.Fifteen patients had a neonatal onset. Thirteen patients (43%) had significant neurological impairment. Chronic renal disease (CRD) occurred in 14 patients (47%) with a median age of onset of 6.5 y (range 1.5–18.6). Renal function further deteriorated in 4 patients within a median period of 5.8 y (range 2–7.4). Of 25 patients investigated at the enzymatic level, 17 were classified mut°, 3 mut- and 5 cblA. Mortality, number of acute decompensations (p = 0.031), median MMA urinary excretion (p = 0.006) and neurological impairment (p < 0.0001) were higher in mut° patients compared to mut-/cblA patients. Concerning the CRD, no difference incidence was found although the onset of CRD occurred earlier in mut° patients and was more severe.Our study provides unique data concerning the progression of renal disease in MMA. Patients with mut° phenotype have a more severe phenotype and probably an earlier and more severe CRD than patients with mut-/cblA phenotype.
Molecular genetics and metabolism, 2013
Chronic renal failure is a well-known long-term complication of methylmalonic aciduria (MMA-uria), occurring even under apparently optimal metabolic management. The onset of renal dysfunction seems to be dependent on the type of defect and vitamin B12-responsiveness. We report on a patient with a vitamin B12-responsive cobalamin A type (cblA) MMA-uria caused by a homozygous stop mutation (p.R145X) in the cobalamin A gene (MMAA). She was diagnosed with chronic kidney disease (CKD) stage III at the age of 12 years. Following re-evaluation, the patient received vitamin B12 (hydroxocobalamin) treatment, resulting in a significant decrease in the concentration of methylmalonic acid (MMA) in urine and plasma. Until age 29 years glomerular filtration rate remained stable probably due to hydroxocobalamin treatment slowing down progression to end-stage renal failure. Kidney biopsies showed non-specific manifestations of chronic interstitial inflammation. The patient received a renal transpla...
Journal of Inherited Metabolic Disease, 2009
SummaryObjectives Isolated methylmalonic acidurias (MMAurias) are caused by deficiency of methylmalonyl‐CoA mutase or by defects in the synthesis of its cofactor 5′‐deoxyadenosylcobalamin. The aim of this study was to evaluate which parameters best predicted the long‐term outcome. Methods Standardized questionnaires were sent to 20 European metabolic centres asking for age at diagnosis, birth decade, diagnostic work‐up, cobalamin responsiveness, enzymatic subgroup (mut0, mut−, cblA, cblB) and different aspects of long‐term outcome. Results 273 patients were included. Neonatal onset of the disease was associated with increased mortality rate, high frequency of developmental delay, and severe handicap. Cobalamin non‐responsive patients with neonatal onset born in the 1970s and 1980s had a particularly poor outcome. A more favourable outcome was found in patients with late onset of symptoms, especially when cobalamin responsive or classified as mut−. Prevention of neonatal crises in pr...