Summary
Intact cultured fibroblasts from patients with deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase release3H2O from [9,10-3H]myristic acid and [9,10-3H]palmitic acid more slowly than normal. The ratio of activity (palmitate/myristate) is also low and the expression (rate with palmitate)2/(rate with myristate) gives good differentiation between affected and unaffected cells. In some patients who have shown hydroxydicarboxylic aciduria when unwell there is reduced3H2O production from [9,10-3H]myristic and [9,10-3H]palmitic acids by intact cultured fibroblasts but normal 3-hydroxyacyl-CoA dehydrogenase activities in disrupted cells. The palmitate/myristate ratio is higher than in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. The basic defect in these patients is still unknown but it is suggested that caution be used over the administration of medium-chain triglyceride.
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References
Bennett MJ (1990) The laboratory diagnosis of inborn errors of mitochondrial fatty acid oxidation.Ann Clin Biochem 27: 519–531.
Carpenter K, Middleton B, Pollitt RJ (1991) The long-chain 3-hydroxyacyl-CoA dehydrogenase of human liver mitochondria.J Inher Metab Dis 14: 321–324.
Carpenter K, Middleton B, Pollitt RJ (1992) Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria.Biochem Biophys Res Commun 183: 443–448.
Duran M, Wanders RJA, de Jager JP et al (1991) 3-Hydroxydicarboxylic aciduria due to long chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency associated with sudden infant death: protective effect of medium-chain triglyceride treatment.Eur J Pediatr 150: 190–195.
El-Fakhri M, Middleton B (1982) The existence of an inner-membrane bound, long-chain 3-hydroxyacyl-CoA dehydrogenase in mammalian mitochondria.Biochim Biophys Acta 713: 270–279.
Hale DE, Thorpe C, Braat K et al (1990) Thel-3-hydroxyacyl-CoA dehydrogenase deficiency. In Tanaka K and Coates PM, eds.Fatty Acid Oxidation: Clinical Biochemical and Molecular Aspects. New York: Alan R Liss, 503–510.
He X-Y, Yang S-Y, Schulz H (1989) Assay ofl-3-hydroxyacyl-CoA dehydrogenase with substrates of different chain lengths.Anal Biochem 180: 105–109.
Jackson S, Bartlett K, Land J et al (1991) Long-chain 3-hydroxyacyl CoA dehydrogenase deficiency.Pediatr Res 29: 406–411.
Kelley RI, Morton H (1988) 3-Hydroxyoctanoic aciduria: identification of a new organic acid in the urine of a patient with non-ketotic hypoglycemia.Clin Chim Acta 175: 19–26.
Manning NJ, Olpin SE, Pollitt RJ, Webley J (1990) Comparison of [9,10-3H]palmitic and [9,10-3H]myristic acids for the detection of fatty acid oxidation defects in intact cultured fibroblasts.J Inher Metab Dis 13: 58–68.
Moore R, Dodge JA, Glasgow JFT et al (1991) A new case of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.Abstracts SSIEM 29th Annual Symposium P-63.
Pollitt RJ (1990) Clinical and biochemical presentations in 20 cases of hydroxydicarboxylic aciduria. In Tanaka K and Coates PM, eds.Fatty Acid Oxidation: Clinical Biochemical and Molecular Aspects. New York: Alan R Liss, 495–502.
Pollitt RJ, Losty H, Westwood A (1987) 3-Hydroxydicarboxylic aciduria: a distinctive type of intermittent dicarboxylic aciduria of possible diagnostic significance.J Inher Metab Dis 10 (Suppl 2): 266–269.
Poll-The BT, Bonnefont JP, Ogier H et al (1988) Familial hypoketotic hypoglycaemia associated with peripheral neuropathy, pigmentary retinopathy and C6-C14 hydroxydicarboxylic aciduria. A new defect in fatty acid oxidation?J Inher Metab Dis 11 (Suppl 2): 183–185.
Sumegi B, Porpaczy Z, Alkonyi I (1991) Kinetic advantages of the interaction between fatty acid β-oxidation enzymes and complexes of the respiratory chain.Biochim Biophys Acta 1081: 121–128.
Thorpe C (1986) A method for the preparation of 3-ketoacyl-CoA derivatives.Anal Biochem 155: 391–394.
Uchida Y, Izai K, Orii T, Hashimoto T (1992) Novel fatty acid β-oxidation enzymes in rat liver mitochondria.J Biol Chem 267: 1034–1041.
Vianey-Liaud C, Divry P, Gregersen N, Mathieu M (1987) The inborn errors of mitochondrial fatty acid oxidation.J Inher Metab Dis 10 (Suppl 2): 159–198.
Vici CD, Burlina AB, Bertini E et al (1991) Recurrent neuropathy and myoglobinuria in a child with long-chain 3-hydroxyacyl-coenzyme A deficiency.J Pediatr 118: 744–746.
Wanders RJA, Ijlst L, van Gennip AH et al (1990) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid β-oxidation.J Inher Metab Dis 13: 311–314.
Watmough NJ, Bhuijyan AKMJ, Bartlett K, Sherratt HSA, Turnbull DM (1989) Skeletal muscle mitochondrial β-oxidation. A study of the products of oxidation of [U-C14]hexadecanoate using HPLC using continuous on-line radiochemical detection.Biochem J 253: 337–343.
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Olpin, S.E., Manning, N.J., Carpenter, K. et al. Differential diagnosis of hydroxydicarboxylic aciduria based on release of3H2O from [9,10-3H]myristic and [9,10-3H]palmitic acids by intact cultured fibroblasts. J Inherit Metab Dis 15, 883–890 (1992). https://doi.org/10.1007/BF01800227
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DOI: https://doi.org/10.1007/BF01800227