Abstract
The term “inborn errors of metabolism” was first used by Garrod in 1909 to define a spectrum of genetically inherited disorders characterised by blocks in the metabolic pathway due to deficient activity of an enzyme in each pathway1. Initially, he described just four disorders — alkaptonuria, albinism, cystinuria and pentosuria. As our knowledge of the human genome has expanded, there has been a vast increase in the number of diseases defined and which may now be diagnosed. It is beyond the scope of this chapter to deal with each of these disorders individually; instead, we hope to raise awareness of the possibility of an underlying metabolic disease and to provide a framework for appropriate investigation.
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References
Garrod AE. Inborn errors of metabolism. Oxford: Oxford University Press, 1909.
Bennett MJ, Rinaldo P. The metabolic autopsy comes of age. Clin Chem 2001; 47(7):1145–6.
Chace DH, DiPerna JC, Mitchell BL, Sgroi B, Hofman LF, Naylor EW. Electrospray tandem mass spectrometry for acylcarnitines in dried post-mortem blood specimens collected at autopsy from infants with unexplained cause of death. Clin Chem 2001;47(7):1166–82.
Roe CR, Ding J. Mitochondrial fatty acid oxidation disorders. In: Scriver CR, Beaudet al, Sly WS, Valle D, editors. The metabolic and molecular basis of inherited disease, 8th Ed. New York: McGraw-Hill, 2000;2297–326.
Bennett MJ, Allison FA, Pollitt RJ, Variend S. Fatty acid oxidation defects as cause of sudden death in infancy. Prog Clin Biol Res 1990;321:349–64.
Ruitenbeek W, Poelis PJ, Turnbull DM, Garavaglia B, Chalmers RA, Taylor RW, et al. Rhabdomyolysis and acute encephalopathy in late-onset medium-chain acyl-CoA dehydrogenase deficiency. J Neurol Neurosurg Psychiatry 1995;58(2):209–14.
Rinaldo P, Raymond K, Barnes CA. Medium-chain acyl-CoA dehydrogenase deficiency: Sudden and unexpected death of a 45-year-old woman. J Inher Metab Dis 1999;22:104.
Gregersen N, Blakemore A, Winter V, Andresen BS, Kolvraa S, Bolund L, et al. Specific diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in dried blood spots by a polymerase chain reaction (PCR) assay detecting a point mutation (G985) in the MCAD gene. Clin Chim Acta 1991;203:23–34.
Brivet M, Boutron A, Slama A, Costa C, Thuillier L, Demaugre F, et al. Defects in activation and transport of fatty acids. J Inher Metab Dis 1999; 22:428–41.
Wanders RJA, Vreken P, Den Boer MEJ, Wijburg FA, Van Gennip AH, Ijlst L. Disorders of mitochondrial fatty acid acyl-CoA (-oxidation. J Inher Metab Dis 1999;22:442–87.
Chalmers RA, Stanley CA, English N, Wigglesworth JS. Mitochondrial carnitine acylcarnitine translocase deficiency presenting as sudden neonatal death. J Pediatr 1997; 131:220–5.
Olpin SE, Allen JC, Bonham JR, Clark S, Clayton PT, Calvin J, et al. Features of CPTI deficiency. J Inher Metab Dis 2001;24:35–42.
Pollitt RJ, Olpin SE, Bonham JR, Cahalane SF, Naughten E. Late-presenting carnitine transport defect. Enzyme and Protein 1993;3:175.
De Vivo DC, Tein I. Primary and secondary disorders of carnitine metabolism. Internat Paediatr 1990;5:134–41.
Manning NJ, Olpin SE, Pollitt RJ, Webley J. A comparison of [9,10-3H]myristic and [9,10-3H]palmitic acids for the detection of fatty acid oxidation in intact cultured fibroblasts. J Inher Metab Dis 1990;13:58–68.
Olpin SE, Manning NJ, Pollitt RJ, Bonham JR, Downing M, Clark S. The use of [9,10-3H]myristate, [9,10-3H]palmitate and [9,10-3H]oleate for the detection and diagnosis of medium- and long-chain fatty acid oxidation disorders in intact cultured fibroblasts. In: Quant PA, Eaton S, editors. Current views of fatty acid oxidation and ketogenesis (Proceedings of the 4th International Symposium on Fatty Acid Oxidation) New York: Plenum Press. 1999.
Olpin SE, Manning NJ, Pollitt RJ, Bonham JR, Downing M, Clark S. Adv Exp Med Biol 1999;466:321–5.
Nada MA, Rhead WJ, Sprecher H, Schulz H, Roe CR Evidence for intermediate channelling in mitochondrial beta-oxidation. J Biol Chem 1995;270:530–5.
Roe CR, Roe DS. Recent developments in the investigation of inherited metabolic disorders using cultured human cells. Mol Genet Metab 1999;68(2):243–57.
Ijlst L, Ruiter JP, Hoovers JM, Jakobs ME, Wanders RJ. Common mis-sense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Characterisation and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene. J Clin Invest 1996;98:1028–33.
Munnich A, Rotig A, Cormier-Daire V, Rustin P. Clinical presentation of respiratory chain deficiency. In: Scriver CR, Beaudet al, Sly WS, Valle D, editors. The metabolic and molecular basis of inherited disease, 8th ed. New York: McGraw-Hill, 2000;2261–74.
Soussi B, Idstrom J, Schersten T, Bylund-Fellenius A. Cytochrome c oxidase and cardiolipin alterations in response to skeletal muscle ischaemia and reperfusion. Acta Physiol Scand 1990;138:481–7.
Pitkanen S, Feigenbaum A, Laframboise R, Robinson BH. NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings. J Inher Metab Dis 1996;19:675–86.
Robinson BH, Ward J, Goodyer P, Baudet A. Respiratory chain defects in the mitochondria of cultured fibroblasts from three patients with lacticacidaemia. J Clin Invest 1986;77:1422–7.
Robinson BH, De Meirlier L, Glerum P, Sherwood G, Becker L. Clinical presentation of mitochondrial respiratory chain defects in NADH-coenzyme Q reductase and cytochrome oxidase. Clues to pathogenesis of Leigh disease. J Pediatr 1987;110:216–22.
Robinson BH, Glerum DM, Chow W, Petrova-Benedict R, Lightowlers R, Capaldi R. The use of skin fibroblast cultures in the detection of respiratory chain defects in patients with lactic acidaemia. Pediatr Res 1990;28:549–55.
Van Erven PM, Ruiten W, Gabreels FM, Renier WO. Mitochondrial encephalopathy: association with an NADH dehydrogenase deficiency. Arch Neurol 1987;44:775–8.
Robinson BH, Oei J, Sherwood WG, Applegarth D, Wong L, Haworth J, et al.. The molecular basis for the two different clinical presentations of classical pyruvate carboxylase deficiency. Am J Hum Genet 1984;36:283–94.
Wanders RJA, Ruiter JPN, Wijburg GA. Studies on mitochondrial oxidative phosphorylation in permeabilised skin fibroblasts: application to mitochondrial encephalomyopathies. Biochim Biophys Acta 1993;181:219–22.
Fischer JC, Ruitenbeek W, Stadhouders AM, Trijbels JM, Sengers RC, Janssen AJ, et al. Investigations of mitochondrial metabolism in small human skeletal muscle biopsy specimens. Improvement of preparation procedure. Clin Chim Acta 1985;145:89–94.
Glerum M, Yanamura W, Capaldi R, Robinson BH. Characterisation of cytochrome oxidase mutations in human fibroblasts. FEBS Lett 1988;236:100–104.
Moreadith RW, Batshaw ML, Ohinishi T, Kerr D, Knox B, Jackson D, et al. Deficiency of ironsulphur clusters of mitochondrial reduced nicotinamide-adenine dineucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis. J Clin Invest 1984;74:685–97.
Rustin P, Chretien D, Bourgeron T, Gerard B, Rotig A, Saudubray JM, et al. Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 1994;228:35–51.
Besley GT, Wraith JE. Lysosomal disorders Mini-symposium: Metabolic disease. Curr Paediatr 1997;7:128–34.
Van Maldergem L, Jauniaux E, Fourneau C, Gillerot Y. Genetic causes of hydrops fetalis. Paediatrics 1992;89:81–6.
Poggi-Travert F, Fournier B, Poll-The BT, Saudubray J-M. Clinical approach to inherited peroxisomal disorders. In: Roels F, De Bie S, Schutgens RB, Besley GT, Eds. Diagnosis of human peroxisomal disorders — a handbook. 1995.
Poggi-Travert F, Fournier B, Poll-The BT, Saudubray J-M. J Inher Metab Dis 1995;18:1–18
Espeel M, Van Limbergen G. Immunocytochemical localisation of peroxisomal proteins in human liver and kidney. J Inher Metab Dis 1995;18:135–54.
Kerckaert I, De Craemer D, Van Limbergen G. Practical guide to morphometry of human per-oxisomes on electron micrographs. J Inher Metab Dis 1995;18:172–80.
Olpin SE, Manning NJ, Pollitt RJ, Clarke S. [9,10-3H]Oleic acid - for the improved detection of long-chain fatty acid oxidation defects in intact cells. J Inher Metab Dis 1997;20: 415–19.
Leonard JV, Morris AAM. Inborn errors of metabolism around the time of birth. Lancet 2000;356:583–7
Beckwith JB. Observations on the pathological anatomy of the sudden infant death syndrome. In: Bergman AB, Beckwith JB, Ray CG, editors. Sudden Infant Death Syndrome. Seattle: University of Washington Press, 1970:83–102.
Sinclair-Smith C, Dinsdale F, Emery J. Evidence of duration and type of illness in children found unexpectedly dead. Arch Dis Child 1976;51:424–8.
Saudubray J-M, Charpentier C. Clinical Phenotypes: Diagnosis/Algorithms. In: Scriver CR, Beaudet al, Sly WS, Valle D, editors. The metabolic and molecular basis of inherited disease, 8th ed. New York: McGraw-Hill, 2000; 1327–403.
Hoffman GF, Athanassopoulos S, Burlina AB, et al. Clinical course early diagnosis, treatment, and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuropaediatrics 1996;27:115–23.
Wilkins B. Head injury ’ abuse or accident? Arch Dis Child 1997;76:393–7.
Tsubata S, Bowles KR, Vatta M, Zintz C, Titus J, Muhonen L. Mutations in human delta-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. J Clin Invest 2000;106(5):655–62.
Peters TJ, Wells G, Oakley CM, Brooksby IA, Jenkins BS, Webb-Peploe MM, et al. Enzymatic analysis of endomyocardial biopsy specimens from patients with cardiomyopathies. Br Heart J 1997;39:1333.
von Kleist-Retzow JC, Cormier-Daire V, de Lonlay P, Parfait B, Chretien D, Rustin P. A high rate of parental consanguinity (20–30%) in cytochrome oxidase deficiency. Am J Hum Genet 1998;63:428.
Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ, Pierpoint ME. Biochemical and molecular basis for mitochondrial cardiomyopathy in neonates and children. J Inher Metab Dis 2000;23: 625–33.
Gibert-Barness E. Cardiovascular system, Part II. In: Gibert-Barness E, editor, Potter’s pathology of the fetus and infant. St. Louis: Mosby Year Book, 1997.
Lamhonwah A-M, Olpin SE, Pollitt RJ, Vianey-Saban C, Divry P, Guffon N, Besley GTN, Onizuka R, De Meirleir LJ, Cvitanovic-Sojat L, Baric I, Dionisi-Vici C, Fumic K, Maradin M, Tein I. Lack of Genotype-phenotype correlation in eleven individuals with novel OCTN2 mutations: Early carnitine therapy prevents cardiomyopathy. Am J Med Genet 2002;111(3):271–84.
Adams PC, Strand RD, Bresnan MJ, Lucky AW. Kinky hair syndrome: serial study of radiological findings with emphasis on the similarity to the battered child syndrome. Paediatr Radiol 1974;56:117–18.
Okun JG, Kolker S, Schulze A, Kohlmuller D, Olgemoller K, Linder M, Hoffmann GF, Wanders RJA, Mayatepek E. A method for quantitative acylcarnitine profiling in human skin fibroblasts using unlabelled palmitic acid: diagnosis of fatty acid oxidation disorders and differentiation between biochemical phenotypes of MCAD deficiency. Biochim Acta 2002;1584:91–8.
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Olpin, S.E., Evans, MJ. (2004). The Investigation of Inherited Metabolic Disease After Death. In: Rutty, G.N. (eds) Essentials of Autopsy Practice. Springer, London. https://doi.org/10.1007/978-1-4471-0637-1_2
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DOI: https://doi.org/10.1007/978-1-4471-0637-1_2
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