Download PDF
Kinder- und Jugendmedizin 2004; 04(03): 107-112
DOI: 10.1055/s-0037-1617821
Stoffwechsel
Schattauer GmbH

Angeborene Störungen des Karnitinzyklus und der Fettsäuren-β-Oxidation

Inborn errors of carnitine cycle and fatty acid β-oxidation
Jörn Oliver Sass
1   Stoffwechsellabor, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Freiburg (Geschäftsführender Direktor: Prof. Dr. med. M. Brandis)
,
Ulrike Veronika Demetz
2   Dr. von Haunersches Kinderspital der LMU München (Direktor: Prof. Dr. med. D. Reinhard)
,
Daniela Skladal
3   Universitätsklinik für Kinder- und Jugendheilkunde Innsbruck, Österreich (Vorstand: Prof. Dr. med. Lothar Bernd Zimmerhackl)
,
Barbara Plecko
4   Universitätsklinik für Kinder- und Jugendheilkunde Graz, Österreich (Vorstand: Prof. Dr. Wilhelm Müller)
› Author Affiliations
Further Information

Publication History

Publication Date:
12 January 2018 (online)

    Permissions and Reprints

Zusammenfassung

Eine intakte Fettsäuren-β-Oxidation ist essenziell für die Deckung des Energiebedarfs nach weitgehender Erschöpfung der Kohlenhydratdepots. Können Fettsäuren aufgrund eines genetischen Defektes nicht adäquat abgebaut werden, kann es in katabolen Stoffwechsellagen zur metabolischen Entgleisung kommen, wobei meist metabolische Azidose und hypoketotische Hypoglykämie Leitsymptome darstellen. Abhängig vom Enzymdefekt sind Leber, Herz und Skelettmuskulatur in unterschiedlichem Ausmaß betroffen. Viele Patienten versterben in der Phase der Erstmanifestation. Eine frühe Diagnosestellung mittels Bestimmung der Azylkarnitine im Blut und der Organischen Säuren im Harn sowie gezielte Therapiemaßnahmen haben die Prognose dieser Patienten in den letzten Jahren wesentlich verbessert. Da Erstmanifestationen von Defekten des Karnitinzyklus und der Fettsäuren-β-Oxidation auch später im Leben möglich sind, sollten diese Krankheiten auch jenseits der Säuglingsperiode in die Differenzialdiagnose einbezogen werden.

Summary

Intact fatty acid β-oxidation is essential for covering energy needs after carbohydrate reservoirs are exhausted in catabolic situations. If fatty acid degradation is impaired due to an inherited defect, catabolism can result in metabolic crises, which are often characterized by metabolic acidosis and hypoketotic hypoglycemia. Depending on the underlying enzyme deficiency liver, heart and skeletal muscles are affected to a different extent. Many patients die during their first metabolic crisis. Early diagnosis by assessment of blood acylcarnitines and urinary organic acids and improved therapeutic means have greatly improved the prognosis of these patients in recent years. Since inborn errors in carnitine cycle and fatty acid β-oxidation can also present later in life, those disorders should also be considered as differential diagnoses beyond infancy.

Schlüsselwörter

Organazidurie - Hypoglykämie - Reye-artiges Syndrom - Kardiomyopathie - Hepatopathie - Rhabdomyolyse

Keywords

Organic aciduria - hypoglycemia - Reye-like syndrome - cardiomyopathy - hepatopathy - rhabdomyolysis
 

  • Literatur

  • 1 Chace DH, Hillman SL, van Hove JLK, Naylor EW. Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry. Clin Chem 1997; 43: 2106-13.
    PubMedGoogle Scholar
  • 2 Corydon MJ, Vockley J, Rinaldo P, Rhead WJ, Kjeldsen M, Winter V. at al Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency. Pediatr Res 2001; 49: 18-23.
    CrossrefPubMedGoogle Scholar
  • 3 den Boer MEJ, Ijlst L, Wijburg FA, Oostheim W, van Werkhoven MA, van Pampus MG. et al. Heterozygosity for the common LCHAD mutation (1528 G > C) is not a major cause of HELLP syndrome and the prevalence of the mutation in the Dutch population is low. Pediatric Res 2000; 48: 151-4.
    CrossrefPubMedGoogle Scholar
  • 4 DiMauro S, DiMauro PMM. Muscle carnitine palmitoyltransferase deficiency and myoglobinuria. Science 1973; 182: 929-31.
    CrossrefPubMedGoogle Scholar
  • 5 Duran M. Disorders of mitochondrial β-oxidation of fatty acids. In: Blau N, Duran M, Blaskovics ME. (eds). Physician’s guide to the laboratory diagnosis of metabolic diseases. London: Chapman & Hall; 1996: 259-76.
    Google Scholar
  • 6 Falik-Borenstein ZC, Jordan SC, Saudubray JM, Brivet M, Demaugre F, Edmond J. et al. Brief report: renal tubular acidosis in carnitine palmitoyltransferase type I deficiency. N Engl J Med 1992; 327: 24-7.
    CrossrefPubMedGoogle Scholar
  • 7 Gempel K, von Praun C, Baumkötter J, Lehnert W, Ensenauer R, Gerbitz K-D, Bauer MF. »Adult« form of muscular carnitine palmitoyltransferase II deficiency: manifestation in a 2-year-old child. Eur J Pediatr 2001; 160: 548-51.
    CrossrefPubMedGoogle Scholar
  • 8 Ibdah JA, Dasouki MJ, Strauss AW. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: Variable expressivity of maternal illness during pregnancy and unusual presentation with infantile cholestasis and hypocalcaemia. J Inher Metab Dis 1999; 22: 811-4.
    CrossrefPubMedGoogle Scholar
  • 9 Ioulianos A, Wells D, Harper JC, Delhanty JD. A successful strategy for preimplantation diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. Prenat Diagn 2000; 20: 593-8.
    CrossrefPubMedGoogle Scholar
  • 10 Kølvraa S, Gregersen N, Christensen E, Hobolth N. In vitro fibroblast studies in a patient with C6-C10-dicarboxylic aciduria: evidence for a defect in general acyl-CoA dehydrogenase. Clin Chim Acta 1982; 126: 53-67.
    CrossrefPubMedGoogle Scholar
  • 11 McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem 1997; 244: 1-14.
    CrossrefPubMedGoogle Scholar
  • 12 Merinero B, Pascual Pascual SI, Pérez-Cerdá C, Gangoiti J, Castro M, Garcia MJ. et al. Adolescent myopathic presentation in two sister with very long-chain acyl-CoA dehydrogenase deficiency. J Inher Metab Dis 1999; 22: 802-10.
    CrossrefPubMedGoogle Scholar
  • 13 Moore R, Glasgow JF, Bingham MA, Dodge JA, Pollitt RJ, Olpin SE, Middleton B, Carpenter K. Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency – diagnosis, plasma carnitine fractions and management in a further patient. Eur J Pediatr 1993; 152: 433-6.
    CrossrefPubMedGoogle Scholar
  • 14 Morris AAM. Disorders of ketogenesis and ketolysis. In: Fernandes J, Saudubray J-M, van den Berghe G. (eds). Inborn metabolic diseases: diagnosis and treatment. 3rd ed.. Berlin, Heidelberg, New York: Springer; 2000: 151-6.
    Google Scholar
  • 15 Roe CR, Coates PM. Mitochondrial fatty acid oxidation disorders. In: Scriver CR, Beaudet AL, Sly WS, Valle D. (eds). The metabolic and molecular bases of inherited disease. 7th ed.. New York: McGraw – Hill; 1997: 1501-33.
    Google Scholar
  • 16 Sherratt HSA, Lightowlers RN, Turnbull DM. Basic sciences and biology of the mitochondrion. In: Applegarth DA, Dimmick JE, Hall JG. (eds). Organelle Diseases. London: Chapman & Hall; 1997: 239-73.
    Google Scholar
  • 17 Skladal D, Sass JO, Geiger H, Geiger R, Mann C, Vreken P. et al. Complications in early diagnosis and treatment of two infants with longchain fatty acid β-oxidation defects. J Pediatr Gastr Nutr 2000; 31: 448-52.
    CrossrefPubMedGoogle Scholar
  • 18 Sperl W. Klinischer Verdacht auf angeborene Stoffwechselstörungen. Wien: Klin Wochenschr; 1992. 104 497-502.
    Google Scholar
  • 19 Stanley CA. Disorders of fatty acid oxidation. In: Fernandes J, Saudubray J-M, van den Berghe G. (eds). Inborn metabolic diseases: diagnosis and treatment. 3rd ed.. Berlin, Heidelberg, New York: Springer; 2000: 139-50.
    Google Scholar
  • 20 Tanaka K, Gregersen N, Ribes A, Kim J, Kølvraa S, Winter V. et al. A survey of the newborn populations in Belgium, Germany, Poland, Czech Republic, Hungary, Bulgaria, Spain, Turkey, and Japan for the G985 variant allele with haplotype analysis at the medium chain Acyl-CoA dehydrogenase gene locus: clinical and evolutionary consideration. Pediatr Res 1997; 41: 201-9.
    PubMedGoogle Scholar
  • 21 Tserng KY, Jin SJ, Kerr DS, Hoppel CL. Urinary 3-hydroxydicarboxylic acids in pathophysiology of metabolic disorders with dicarboxylic aciduria. Metabolism 1991; 7: 676-82.
    Google Scholar
  • 22 Tyni T, Palotie A, Viinikka L, Valanne L, Salo MK, von Döbeln U. et al. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency with the G1528C mutation: clinical presentation of thirteen patients. J Pediatr 1997; 130: 67-76.
    CrossrefPubMedGoogle Scholar
  • 23 Ventura FV, Costa CG, Struys EA, Ruiter J, Allers P, Ijlst L. et al. Quantitative acylcarnitine profiling in fibroblasts using (U-13C) palmitic acid: improved tool for the diagnosis of fatty acid oxidation defects. Clin Chim Acta 1999; 281: 1-17.
    CrossrefPubMedGoogle Scholar
  • 24 Vianey-Saban C, Divry P, Brivet M, Nada M, Zabot MT, Mathieu M. et al. Mitochondrial very-long-chain acyl-coenzyme A dehydrogenase deficiency: clinical characteristics and diagnostic considerations in 30 patients. Clin Chim Acta 1998; 269: 43-62.
    CrossrefPubMedGoogle Scholar
  • 25 Wanders RJA, Vreken P, den Boer MEJ, Wijburg FA, van Gennip AH, Ijlst L. Disorders of mitochondrial fatty acyl-CoA β-oxidation. J Inher Metab Dis 1999; 22: 442-87.
    CrossrefPubMedGoogle Scholar
  • 26 Wilcken B, Leung K-C, Hammond J, Kamath R, Leonard JV. Pregnancy and fetal long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency. Lancet 1993; 341: 407-8.
    CrossrefPubMedGoogle Scholar
  • 27 Zschocke J, Penzien JM, Bielen R, Casals N, Aledo R, Pié J. et al. The diagnosis of mitochondrial HMG-CoA synthase deficiency. J Pediatr 2002; 140: 778-80.
    CrossrefPubMedGoogle Scholar