Summary
In a series of 137 patients with methylmalonic acidaemia (MMA) and propionic acidaemia (PA) diagnosed since the early 1970s, we report in more detail 81 patients (51 MMA and 30 PA) diagnosed between 1988 and 2005. In this series, 14% of patients died at initial access revealing the disease before or despite treatment, 18% died later, and the remainder (68%) are still alive. All patients were treated with the same protocol of enteral feeds with a low-protein diet adjusted to individual tolerance, carnitine, antibiotics, and only occasional use of an amino acid (AA) mixture. There was intensive follow-up and monitoring using measurements of urinary urea. Thirty-nine patients with severe forms, followed for more than 3 years, are analysed in particular detail. Of the 17 PA patients, 6 had moderate disability (all neonatal-onset forms), whereas 11 were normal or slightly delayed in their mental development. Four presented with cardiomyopathy, of whom 2 died. Of the 22 MMA patients, 13 presented in the neonatal period, of whom 3 died later, 2 are in renal failure and only 5 are still alive and have a normal or slightly delayed mental development. In the 9 patients with late-onset forms, there were no deaths and all patients but one have normal mental development. Among the 39 patients, only 40% were given an AA supplement at 3 years, and 50% between 6 and 11 years. The actual intake of natural protein was 0.92, 0.78 and 0.77 g/kg per day at 3, 6 and 11 years, respectively, in patients without AA supplementation, whereas it was 0.75, 0.74 and 0.54 g/kg per day in the group who received small quantities of AA (0.4–0.6 g/kg per day). In both groups, feeding disorders were frequent: 55% at 3 years, 35% at 6 years and 12% at 11 years. Many patients were given a food supplement by tube overnight or were even exclusively tube fed: 60% at 3 years, 48% at 6 years and still 27% at 11 years. Growth velocity was near the normal values. Plasma valine and isoleucine were low to very low, as were leucine and phenylalanine but to a lesser extent. Albumin, vitamins, trace elements and markers of bone metabolism were within the normal values. IGF1, 24-hour urine calcium and body mass density were low. Body composition showed a normal to low lean mass and a normal to high fat mass.
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Abbreviations
- AA:
-
amino acid
- BCAA:
-
branched-chain amino acids
- IGF1:
-
insulin-like growth factor 1
- MMA:
-
methylmalonic acidaemia
- MSUD:
-
maple syrup urine disease
- PA:
-
propionic acidaemia
- PKU:
-
phenylketonuria
- PTH:
-
parathyroid hormone
References
Bain MD, Nussey SS, Jones M, Chalmers RA (1995) Use of human somatotrophin in the treatment of a patient with methylmalonic aciduria. Eur J Pediatr 154: 850–852.
Baumgartner ER, Viardot C (1995) Long-term follow-up of 77 patients with isolated methylmalonic acidaemia. J Inherit Metab Dis 18: 138–142.
Burns SP, Iles RA, Saudubray JM, Chalmers RA (1996) Propionylcarnitine excretion is not affected by metronidazole administration to patients with disorders of propionate metabolism. Eur J Pediatr 155: 31–35.
Dhawan A, Mitry RR, Hughes RD (2006) Hepatocyte transplantation for liver-based metabolic disorders. J Inherit Metab Dis 29: 431–435.
Dionisi-Vici C, Deodato F, Röschinger W, Rhead WJ, Wilcken B (2006) ‘Classical’ organic acidurias, propionic, methylmalonic and isovaleric acidurias, long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis 29: 383–389.
Kelts DG, Ney D, Bay C, Saudubray JM, Nyhan WL (1985) Studies on requirements for amino acids in infants with disorders of amino acid metabolism. I. Effect of alanine. Pediatr Res 51: 86–91.
Leonard JV, Daish P, Naughten ER, Bartlett K (1984) The management and long-term outcome of organic acidaemias. J Inherit Metab Dis 7(Supplement 1): 13–17.
Marsden D, Barshop BA, Capistrano-Estrada S, et al (1994) Anabolic effect of human growth hormone: management of inherited disorders of catabolic pathways. Biochem Med Metab Biol 52: 145–154.
Matsui SM, Mahoney MJ, Rosenberg LE (1983) The natural history of the inherited methylmalonic acidemias. N Engl J Med 308: 857–861.
Ney D, Bay C, Saudubray JM, et al (1985) An evaluation of protein requirements in methylmalonic acidaemia. J Inherit Metab Dis 8: 132–142.
11O Ogier de Baulny H, Benoist JF, Rigal O, Touati G, Rabier D, Saudubray JM (2005) Methylmalonic and propionic acidaemias: management and outcome. J Inherit Metab Dis 28: 415–423.
Roe CR, Hoppel CL, Stacey TE, Chalmers RA, Treacey BM, Millington DS (1983) Metabolic response to carnitine in methylmalonic aciduria: an effective strategy for elimination of propionyl groups. Arch Dis Child 58: 916–920.
Sbai D, Narcy C, Thompson GN, et al (1994) Contribution of odd-chain fatty acid oxidation to propionate production in disorders of propionate metabolism. Am J Clin Nutr 59: 1332–1337.
Schlenzig JS, Poggi-Travert F, Laurent J, et al (1995) Liver transplantation in two cases of propionic acidaemia. J Inherit Metab Dis 18: 448–461.
Sokal EM (2006) Liver transplantation for inborn errors of liver metabolism: a review. J Inherit Metab Dis 29: 426–430.
Thompson GN, Chalmers RA, Walter JH, et al (1990) The use of metronidazole in management of methylmalonic and propionic acidemias. Eur J Pediatr 149: 792–796.
Touati G, Ogier de Baulny H, Rabier D, et al (2003) Beneficial effects of growth hormone treatment in children with methylmalonic and propionic acidurias. J Inherit Metab Dis 26(Supplement 2): 40.
Van der Meer S, Poggi F, Spada M, et al (1994) Clinical outcome of long-term management of 26 patients with vitamin B12-unresponsive methylmalonic acidemia. J Pediatr 125: 903–908.
Van der Meer S, Poggi F, Spada M, et al (1996) Clinical outcome and long-term management of 17 patients with propionic acidaemia. Eur J Pediatr 155: 205–210.
Walter JH, Thompson GN, Leonard JV, Bartlett K, Halliday K (1989) Contribution of amino acid catabolism to propionate production in methylmalonic acidaemia. Lancet 1: 1298–1299.
Yannicelli S (2006) Nutrition therapy of organic acidaemia with amino acid based medical foods: emphasis on metabolic and propionic acidaemias. J Inherit Metab Dis 29: 281–287.
Yannicelli S, Acosta PB, Velazquez A, et al (2003) Improved growth and nutrition status in children with methylmalonic or propionic acidemia fed an elemental medical food. Mol Genet Metab 80: 181–188.
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Communicating editor: Jean-Marie Saudubray
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Touati, G., Valayannopoulos, V., Mention, K. et al. Methylmalonic and propionic acidurias: Management without or with a few supplements of specific amino acid mixture. J Inherit Metab Dis 29, 288–298 (2006). https://doi.org/10.1007/s10545-006-0351-7
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DOI: https://doi.org/10.1007/s10545-006-0351-7