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C6-C10-dicarboxylic aciduria: investigations of a patient with riboflavin responsive multiple acyl-CoA dehydrogenation defects.
Pediatr Res. 1982 Oct; 16(10):861-8.PR

Abstract

The abnormal metabolites-adipic, suberic, and sebacic acids-were detected in large amounts in the urine of a boy during a Reye's syndrome-like crisis. Substantial amounts of 5-OH-caproic acid, caproylglycine, glutaric acid, and 3-OH-butyric acid and moderately elevated amounts of ethylmalonic acid, methylsuccinic acid, 3-OH-isovaleric acid, and isovalerylglycine were also found. These metabolites were consistently present in urine samples collected in the boy's habitual condition after the attack. 1-[14C]-Palmitic acid was oxidized at a normal rate, whereas U-[14C]-Palmitic acid was oxidized at a reduced rate in cultured skin fibroblasts from the patient, thus indicating a defect at the level of medium- and/or short-chain fatty acid oxidation. Riboflavin medication (100 mg three times a day) significantly reduced the excreted amounts of pathologic metabolites, suggesting a flavineadeninedinucleotide-related acyl-CoA dehydrogenation defect as the cause of the disease. Carnitine in plasma was low in the patient (6 mumole/liter, controls 26-74 mumole/liter), suggesting carnitine deficiency as a secondary effect of the acyl-CoA dehydrogenation deficiency. The present patient, who presented with a Reye's syndrome-like attack, suffers from impaired dehydrogenation of acyl-CoA resulting in accumulation of acyl-CoA in the cells. Attacks with similar symptoms are seen in other acyl-CoA dehydrogenation deficiencies, such as glutaric aciduria types I and II, other types of C6-C10-dicarboxylic acidurias and isovaleric acidemia. Reduced flow through the acyl-CoA dehydrogenation steps may therefore be an ethiologic factor in Reye's syndrome. Several of the accumulated acyl-CoA's are toxic and may be responsible for some of the symptoms. The low carnitine level in plasma and the elevated esterified carnitine excretion in the present patient indicate that acyl-CoA accumulation may cause a functional carnitine deficiency by sequestration of carnitine as acyl-carnitines. As the inborn defect, systemic carnitine deficiency may exhibit symptoms like those of Reye's syndrome, it may be speculated whether functional carnitine deficiency in patients with accumulated acyl-CoA is another causal factor in the development of the symptoms during attacks.

Authors

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Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7145508

Citation

Gregersen, N, et al. "C6-C10-dicarboxylic Aciduria: Investigations of a Patient With Riboflavin Responsive Multiple acyl-CoA Dehydrogenation Defects." Pediatric Research, vol. 16, no. 10, 1982, pp. 861-8.
Gregersen N, Wintzensen H, Christensen SK, et al. C6-C10-dicarboxylic aciduria: investigations of a patient with riboflavin responsive multiple acyl-CoA dehydrogenation defects. Pediatr Res. 1982;16(10):861-8.
Gregersen, N., Wintzensen, H., Christensen, S. K., Christensen, M. F., Brandt, N. J., & Rasmussen, K. (1982). C6-C10-dicarboxylic aciduria: investigations of a patient with riboflavin responsive multiple acyl-CoA dehydrogenation defects. Pediatric Research, 16(10), 861-8.
Gregersen N, et al. C6-C10-dicarboxylic Aciduria: Investigations of a Patient With Riboflavin Responsive Multiple acyl-CoA Dehydrogenation Defects. Pediatr Res. 1982;16(10):861-8. PubMed PMID: 7145508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - C6-C10-dicarboxylic aciduria: investigations of a patient with riboflavin responsive multiple acyl-CoA dehydrogenation defects. AU - Gregersen,N, AU - Wintzensen,H, AU - Christensen,S K, AU - Christensen,M F, AU - Brandt,N J, AU - Rasmussen,K, PY - 1982/10/1/pubmed PY - 1982/10/1/medline PY - 1982/10/1/entrez SP - 861 EP - 8 JF - Pediatric research JO - Pediatr. Res. VL - 16 IS - 10 N2 - The abnormal metabolites-adipic, suberic, and sebacic acids-were detected in large amounts in the urine of a boy during a Reye's syndrome-like crisis. Substantial amounts of 5-OH-caproic acid, caproylglycine, glutaric acid, and 3-OH-butyric acid and moderately elevated amounts of ethylmalonic acid, methylsuccinic acid, 3-OH-isovaleric acid, and isovalerylglycine were also found. These metabolites were consistently present in urine samples collected in the boy's habitual condition after the attack. 1-[14C]-Palmitic acid was oxidized at a normal rate, whereas U-[14C]-Palmitic acid was oxidized at a reduced rate in cultured skin fibroblasts from the patient, thus indicating a defect at the level of medium- and/or short-chain fatty acid oxidation. Riboflavin medication (100 mg three times a day) significantly reduced the excreted amounts of pathologic metabolites, suggesting a flavineadeninedinucleotide-related acyl-CoA dehydrogenation defect as the cause of the disease. Carnitine in plasma was low in the patient (6 mumole/liter, controls 26-74 mumole/liter), suggesting carnitine deficiency as a secondary effect of the acyl-CoA dehydrogenation deficiency. The present patient, who presented with a Reye's syndrome-like attack, suffers from impaired dehydrogenation of acyl-CoA resulting in accumulation of acyl-CoA in the cells. Attacks with similar symptoms are seen in other acyl-CoA dehydrogenation deficiencies, such as glutaric aciduria types I and II, other types of C6-C10-dicarboxylic acidurias and isovaleric acidemia. Reduced flow through the acyl-CoA dehydrogenation steps may therefore be an ethiologic factor in Reye's syndrome. Several of the accumulated acyl-CoA's are toxic and may be responsible for some of the symptoms. The low carnitine level in plasma and the elevated esterified carnitine excretion in the present patient indicate that acyl-CoA accumulation may cause a functional carnitine deficiency by sequestration of carnitine as acyl-carnitines. As the inborn defect, systemic carnitine deficiency may exhibit symptoms like those of Reye's syndrome, it may be speculated whether functional carnitine deficiency in patients with accumulated acyl-CoA is another causal factor in the development of the symptoms during attacks. SN - 0031-3998 UR - https://www.unboundmedicine.com/medline/citation/7145508/C6_C10_dicarboxylic_aciduria:_investigations_of_a_patient_with_riboflavin_responsive_multiple_acyl_CoA_dehydrogenation_defects_ L2 - http://dx.doi.org/10.1203/00006450-198210000-00012 DB - PRIME DP - Unbound Medicine ER -