Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Apr;75(4):1124–1130. doi: 10.1172/JCI111806

Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome.

I Bernardini, W B Rizzo, M Dalakas, J Bernar, W A Gahl
PMCID: PMC425435  PMID: 3988933

Abstract

Plasma and urine free and acyl carnitine were measured in 19 children with nephropathic cystinosis and renal Fanconi syndrome. Each patient exhibited a deficiency of plasma free carnitine (mean 11.7 +/- 4.0 [SD] nmol/ml) compared with normal control values (42.0 +/- 9.0 nmol/ml) (P less than 0.001). Mean plasma acyl carnitine in the cystinotic subjects was normal. Four subjects with Fanconi syndrome but not cystinosis displayed the same abnormal pattern of plasma carnitine levels; controls with acidosis or a lysosomal storage disorder (Fabry disease), but not Fanconi syndrome, had entirely normal plasma carnitine levels. Two postrenal transplant subjects with cystinosis but without Fanconi syndrome also had normal plasma carnitine levels. Absolute amounts of urinary free carnitine were elevated in cystinotic individuals with Fanconi syndrome. In all 21 subjects with several different etiologies for the Fanconi syndrome, the mean fractional excretion of free carnitine (33%) as well as acyl carnitine (26%) greatly exceeded normal values (3 and 5%, respectively). Total free carnitine excretion in Fanconi syndrome patients correlated with total amino acid excretion (r = 0.76). Two cystinotic patients fasted for 24 h and one idiopathic Fanconi syndrome patient fasted for 5 h showed normal increases in plasma beta-hydroxybutyrate and acetoacetate, which suggested that hepatic fatty acid oxidation was intact despite very low plasma free carnitine levels. Muscle biopsies from two cystinotic subjects with Fanconi syndrome and plasma carnitine deficiency had 8.5 and 13.1 nmol free carnitine per milligram of noncollagen protein, respectively (normal controls, 22.3 and 17.1); total carnitines were 11.8 and 13.3 nmol/mg noncollagen protein (controls 33.5, 20.0). One biopsy revealed a mild increase in lipid droplets. The other showed mild myopathic features with variation in muscle fiber size, small vacuoles, and an increase in lipid droplets. In renal Fanconi syndrome, failure to reabsorb free and acyl carnitine results in a secondary plasma and muscle free carnitine deficiency.

Full text

PDF
1124

Images in this article

1128Image
on p.1128

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bartel L. L., Hussey J. L., Shrago E. Perturbation of serum carnitine levels in human adults by chronic renal disease and dialysis therapy. Am J Clin Nutr. 1981 Jul;34(7):1314–1320. doi: 10.1093/ajcn/34.7.1314. [DOI] [PubMed] [Google Scholar]
  2. Battistella P. A., Vergani L., Donzelli F., Rubaltelli F. F., Angelini C. Plasma and urine carnitine levels during development. Pediatr Res. 1980 Dec;14(12):1379–1379. doi: 10.1203/00006450-198012000-00024. [DOI] [PubMed] [Google Scholar]
  3. Bertoli M., Battistella P. A., Vergani L., Naso A., Gasparotto M. L., Romagnoli G. F., Angelini C. Carnitine deficiency induced during hemodialysis and hyperlipidemia: effect of replacement therapy. Am J Clin Nutr. 1981 Aug;34(8):1496–1500. doi: 10.1093/ajcn/34.8.1496. [DOI] [PubMed] [Google Scholar]
  4. Bieber L. L., Emaus R., Valkner K., Farrell S. Possible functions of short-chain and medium-chain carnitine acyltransferases. Fed Proc. 1982 Oct;41(12):2858–2862. [PubMed] [Google Scholar]
  5. Blank D. W., Nanji A. A. Ketone interference in estimation of urinary creatinine; effect on creatinine clearance in diabetic ketoacidosis. Clin Biochem. 1982 Dec;15(6):279–280. doi: 10.1016/s0009-9120(82)96774-1. [DOI] [PubMed] [Google Scholar]
  6. Bohmer T., Bergrem H., Eiklid K. Carnitine deficiency induced during intermittent haemodialysis for renal failure. Lancet. 1978 Jan 21;1(8056):126–128. doi: 10.1016/s0140-6736(78)90422-1. [DOI] [PubMed] [Google Scholar]
  7. Broquist H. P. Carnitine biosynthesis and function. Introductory remarks. Fed Proc. 1982 Oct;41(12):2840–2842. [PubMed] [Google Scholar]
  8. Butler J. D., Zatz M. Pantethine depletes cystinotic fibroblasts of cystine. J Pediatr. 1983 May;102(5):796–798. doi: 10.1016/s0022-3476(83)80262-5. [DOI] [PubMed] [Google Scholar]
  9. Carrier H. N., Berthillier G. Carnitine levels in normal children and adults and in patients with diseases muscle. Muscle Nerve. 1980 Jul-Aug;3(4):326–334. doi: 10.1002/mus.880030409. [DOI] [PubMed] [Google Scholar]
  10. Cederblad G., Lindstedt S. Excretion of L-carnitine in man. Clin Chim Acta. 1971 Jun;33(1):117–123. doi: 10.1016/0009-8981(71)90258-0. [DOI] [PubMed] [Google Scholar]
  11. Cederblad G., Lindstedt S., Lundholm K. Concentration of carnitine in human muscle tissue. Clin Chim Acta. 1974 Jun 28;53(3):311–321. doi: 10.1016/0009-8981(74)90270-8. [DOI] [PubMed] [Google Scholar]
  12. Engel A. G., Angelini C. Carnitine deficiency of human skeletal muscle with associated lipid storage myopathy: a new syndrome. Science. 1973 Mar 2;179(4076):899–902. doi: 10.1126/science.179.4076.899. [DOI] [PubMed] [Google Scholar]
  13. Engel A. G., Rebouche C. J. Carnitine metabolism and inborn errors. J Inherit Metab Dis. 1984;7 (Suppl 1):38–43. doi: 10.1007/BF03047372. [DOI] [PubMed] [Google Scholar]
  14. Engel A. G., Rebouche C. J., Wilson D. M., Glasgow A. M., Romshe C. A., Cruse R. P. Primary systemic carnitine deficiency. II. Renal handling of carnitine. Neurology. 1981 Jul;31(7):819–825. doi: 10.1212/wnl.31.7.819. [DOI] [PubMed] [Google Scholar]
  15. Engel W. K. Selective and nonselective susceptibility of muscle fiber types. A new approach to human neuromuscular diseases. Arch Neurol. 1970 Feb;22(2):97–117. doi: 10.1001/archneur.1970.00480200003001. [DOI] [PubMed] [Google Scholar]
  16. Frohlich J., Seccombe D. W., Hahn P., Dodek P., Hynie I. Effect of fasting on free and esterified carnitine levels in human serum and urine: correlation with serum levels of free fatty acids and beta-hydroxybutyrate. Metabolism. 1978 May;27(5):555–561. doi: 10.1016/0026-0495(78)90022-7. [DOI] [PubMed] [Google Scholar]
  17. Gahl W. A., Bashan N., Tietze F., Bernardini I., Schulman J. D. Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis. Science. 1982 Sep 24;217(4566):1263–1265. doi: 10.1126/science.7112129. [DOI] [PubMed] [Google Scholar]
  18. Gahl W. A., Tietze F., Bashan N., Bernardini I., Raiford D., Schulman J. D. Characteristics of cystine counter-transport in normal and cystinotic lysosome-rich leucocyte granular fractions. Biochem J. 1983 Nov 15;216(2):393–400. doi: 10.1042/bj2160393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gusmano R., Oleggini R., Perfumo F. Plasma carnitine concentrations and dyslipidemia in children on maintenance hemodialysis. J Pediatr. 1981 Sep;99(3):429–432. doi: 10.1016/s0022-3476(81)80338-1. [DOI] [PubMed] [Google Scholar]
  20. McGarry J. D., Foster D. W. An improved and simplified radioisotopic assay for the determination of free and esterified carnitine. J Lipid Res. 1976 May;17(3):277–281. [PubMed] [Google Scholar]
  21. Ohtani Y., Nishiyama S., Matsuda I. Renal handling of free and acylcarnitine in secondary carnitine deficiency. Neurology. 1984 Jul;34(7):977–979. doi: 10.1212/wnl.34.7.977. [DOI] [PubMed] [Google Scholar]
  22. Olsen C. An enzymatic fluorimetric micromethod for the determination of acetoacetate, -hydroxybutyrate, pyruvate and lactate. Clin Chim Acta. 1971 Jul;33(2):293–300. doi: 10.1016/0009-8981(71)90486-4. [DOI] [PubMed] [Google Scholar]
  23. Rebouche C. J., Engel A. G. Carnitine metabolism and deficiency syndromes. Mayo Clin Proc. 1983 Aug;58(8):533–540. [PubMed] [Google Scholar]
  24. Rebouche C. J., Engel A. G. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport. J Clin Invest. 1984 Mar;73(3):857–867. doi: 10.1172/JCI111281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rebouche C. J., Engel A. G. Primary systemic carnitine deficiency: I. Carnitine biosynthesis. Neurology. 1981 Jul;31(7):813–818. doi: 10.1212/wnl.31.7.813. [DOI] [PubMed] [Google Scholar]
  26. Roe C. R., Millington D. S., Maltby D. A., Bohan T. P., Hoppel C. L. L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. J Clin Invest. 1984 Jun;73(6):1785–1788. doi: 10.1172/JCI111387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schmidt-Sommerfeld E., Penn D., Wolf H. Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation. J Pediatr. 1983 Jun;102(6):931–935. doi: 10.1016/s0022-3476(83)80027-4. [DOI] [PubMed] [Google Scholar]
  28. Spielberg S. P., Kramer L. I., Goodman S. I., Butler J., Tietze F., Quinn P., Schulman J. D. 5-oxoprolinuria: biochemical observations and case report. J Pediatr. 1977 Aug;91(2):237–241. doi: 10.1016/s0022-3476(77)80819-6. [DOI] [PubMed] [Google Scholar]
  29. Stanley C. A., Baker L. Hyperinsulinism in infancy: diagnosis by demonstration of abnormal response to fasting hypoglycemia. Pediatrics. 1976 May;57(5):702–711. [PubMed] [Google Scholar]
  30. Thoene J. G., Oshima R. G., Crawhall J. C., Olson D. L., Schneider J. A. Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo. J Clin Invest. 1976 Jul;58(1):180–189. doi: 10.1172/JCI108448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tripp M. E., Katcher M. L., Peters H. A., Gilbert E. F., Arya S., Hodach R. J., Shug A. L. Systemic carnitine deficiency presenting as familial endocardial fibroelastosis: a treatable cardiomyopathy. N Engl J Med. 1981 Aug 13;305(7):385–390. doi: 10.1056/NEJM198108133050707. [DOI] [PubMed] [Google Scholar]
  32. Waber L. J., Valle D., Neill C., DiMauro S., Shug A. Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport. J Pediatr. 1982 Nov;101(5):700–705. doi: 10.1016/s0022-3476(82)80294-1. [DOI] [PubMed] [Google Scholar]
  33. Ware A. J., Burton W. C., McGarry J. D., Marks J. F., Weinberg A. G. Systemic carnitine deficiency. Report of a fatal case with multisystemic manifestations. J Pediatr. 1978 Dec;93(6):959–964. doi: 10.1016/s0022-3476(78)81219-0. [DOI] [PubMed] [Google Scholar]
  34. Watkins P. J. The effect of ketone bodies on the determination of creatinine. Clin Chim Acta. 1967 Nov;18(2):191–196. doi: 10.1016/0009-8981(67)90156-8. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES