Abstract
Comprehensive data on 30 patients with propionic acidaemia, diagnosed by selective screening for inborn errors of metabolism, are presented. The most valuable diagnostic metabolites found were methylcitric-, 3-hydroxypropionic-, and 2-methyl-3-oxovaleric acids. Hyperlysinaemia and hyperlysinuria are also characteristic findings in this disease. The metabolic pattern found in propionic acidaemia is discussed extensively as are enzymatic findings. Residual activity of propionyl-CoA carboxylase is neither a predictive marker for severity nor for outcome of the disease. Propionate fixation assay were less reliable for confirmation of propionic acidaemia and of no prognostic value. Clinical presentation of the disease is discussed in detail. Besides the well-known unspecific findings (poor appetite, feeding difficulties, vomiting, dehydration, weight loss, muscular hypotonia, dyspnoea, somnolence, apathy, convulsion, coma, severe metabolic acidosis, hyperammonaemia) various skin abnormalities have been detected in about 50% of all patients. In 27% “dermatitis acidemica” was found.
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Abbreviations
- GC-MS :
-
gas chromatography-mass spectrometry
- MCC :
-
3-methylcrotonyl-CoA carboxylase
- OLCFA :
-
odd-numbered long-chain fatty acids
- PA :
-
propionic acidaemia
- PC :
-
pyruvate carboxylase
- PCC :
-
propionyl-CoA carboxylase
- P-CoA :
-
propionyl-CoA
- SSS-syndrome :
-
staphylococcal scalded skin syndrome
- MSUD :
-
maple syrup urine disease
References
Ando T, Rasmussen K, Nyhan WL, Hull D (1972) β-Hydroxypropionate: significance of β-oxidation of propionate in patients with propionic acidemia and methylmalonic acidemia. Proc Natl Acad Sci USA 69:2807–2811
Ando T, Rasmussen K, Wright JM, Nyhan WL (1972) Isolation and identification of methylcitrate, a major metabolic product of propionate in patients with propionic acidemia. J Biol Chem 247:2200–2204
Bachmann C (1984) Treatment of congenital hyperammonemias. Enzyme 32:56–64
Bain MD, Jones M, Borrielo SP, Reed PJ, Tracey BM, Chalmers RA, Stacey TE (1988) Contribution of gut bacterial metabolism to human metabolic disease. Lancet I:1078–1079
Baumgartner ER, Suormala TM, Wick H, Probst A, Blauenstein U, Bachmann C, Vest M (1989) Biotinidase deficiency: a cause of subacute necrotizing encephalomyelopathy (Leigh syndrome). Report of a case with lethal outcome. Pediatr Res 26:260–266
Behbehani AW, Lehnert W, Langenbeck U, Luthe H, Baumgarter R (1984) Propionacidämie mit Myelinisierungsstörungen im ZNS. Klin Pädiatr 196:106–110
Blom W, Huijmans JGM, Berg GB van den (1989) A clinical biochemist's view of the investigation of suspected inherited metabolic disease. J Inherited Metab Dis 12 [Suppl 1]:64–88
Boehles H, Lehnert W (1984) The effect of intravenousl-carnitine on propionic acid excretion in acute propionic acidaemia. Eur J Pediatr 143:61–63
Brandaenges S, Josephson S, Mahlen A, Morch L, Sweetman L, Vallen S (1977) Stereochemistry of the methylcitric acids formed in the citrate synthase reaction with propionyl-CoA. Acta Chem Scand B 31:628–630
Chalmers RA, Lawson AM (1982) Organic acids in man. The analytical chemistry, biochemistry, and diagnosis of the organic acidurias. Chapman and Hall, London, p 301
Chalmers RA, Roe CR, Stacey TE, Hoppel CR (1984) Urinary excretion ofl-carnitine and acylcarnitine by patients with disorders of organic acids metabolism: evidence for secondary insufficiency of L-carnitine. Pediatr Res 18:1325–1328
Childs B, Nyhan WL, Borden M, Bard L, Cooke RE (1961) Idiopathic hyperglycinemia and hyperglycinuria: a new disorder of amino acid metabolism. J Pediatr 27:522–538
Coude FX, Sweetman L, Nyhan WL (1979) Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia. J Clin Invest 64:1544–1551
Coulombe JT, Shih VE, Levy HL (1981) Massachusetts metabolic disorders screening program. II. Methylmalonic aciduria. Pediatr 67:26–31
Divry P, Vianey-Liand C, Cotte J (1987) Routine gas chromatographymass spectrometry analysis of urinary organic acids. Results over a three-year period. Biomed Environ Mass Spectrom 14:663–668
Duran M, Gompertz D, Bruinvis C, Ketting D, Wadman SK (1978) The variability of metabolite excretion in propionic acidemia. Clin Chim Acta 82:93–99
Duran M, Bruinvis L, Ketting D, Kamerling JP, Wadman SK, Schutgens RB (1982) The identification of (E)-2-methylglutaconic acid, a new isoleucine metabolite, in the urine of patients with β-ketothiolase deficiency, propionic acidemia, and methylmalonic acidemia. Biomed Mass Spectrom 9:1–5
Duran M, Ketting D, Beckeringh TE, Leupold D, Wadman SK (1986) Direct identification of propionylcarnitine in propionic acidemia: Biochemical and clinical results of orall-carnitine supplementation. J Inherited Metab Dis 9:202–207
Erasmus E, Miunie LJ, Schyff CJ van den, Reinecke CJ (1990) The use of3H-propionic acid and15N-alanine in investigating the formation pathways of a newly detected metabolite propionylalanine in propionic acidemia. Vth International Congress, Inborn Errons of Metabolism. Pacific Grove, CA, USA, 1990. Abstract OC 10.4
Glasgow AM, Chase P (1976) Effect of propionic acid on fatty acid oxidation and ureagenesis. Pediatr Res 10:683–686
Gompertz D, Bau DCK, Storrs CN, Peters TJ, Hughes EA (1970) Localisation of enzymic defect in propionic acidemia. Lancet I:1140–1143
Goodall GJ, Johannssen W, Wallace JC, Keech DB (1985) Sheep liver propionyl CoA carboxylase: purification and some molecular properties. Ann NY Acad Sci 47:396–397
Gravel RA, Lam KF, Scully KJ, Hsia YE (1977) Genetic complementation of propionyl CoA carboxylase deficiency in cultured human fibroblasts. Am J Hum Genet 29:378–388
Gregersen N (1979) Studies on the effect of saturated and unsaturated shortchain monocarboxylic acids on the energy metabolism of rat liver mitochondria. Pediatr Res 13:1227–1230
Greter J, Lindstedt S, Seeman H, Steen G (1980) 2-Hydroxy-2-methylsuccinic acid — A urinary metabolite in propionyl-CoA carboxylase deficiency. Clin Chim Acta 106:103–106
Haase FC, Beegen H, Allen SHK (1984) Propionyl coenzyme A carboxylase of Mycobacterium smegmatis. Eur J Biochem 140:147–151
Harding BN, Leonard JV, Erdohazi M (1991) Piopionic acidemia: a neuropathological study of two patients presenting in infancy. Neuropathol Appl Neurobiol 17:133–138
Hillman RE, Otto EF (1974) Inhibition of glycine-serine interconversion in cultured human fibroblasts by products of isoleucine catabolism. Pediatr Res 8:941
Hillman RE, Sowers LH, Cohen JL (1973) Inhibition of glycine oxidation in cultured fibroblasts by isoleucine. Pediatr Res 7:945–947
Hommes FA, Kuipers JRG, Elema JD, Jamsen JF, Jonxis JHP (1968) Propionic acidemia, a new inborn error of metabolism. Pediatr Res 2:519–524
Hutchingson RJ, Bunell K, Thoene JG (1985) Suppression of granulopoietic progenitor cell proliferation by metabolites of the branched-chain amino acids. J Pediatr 106:62–65
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Lehnert, W., Sperl, W., Suormala, T. et al. Propionic acidaemia: clinical, biochemical and therapeutic aspects. Eur J Pediatr 153 (Suppl 1), S68–S80 (1994). https://doi.org/10.1007/BF02138781
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DOI: https://doi.org/10.1007/BF02138781