Original article| Volume 24, ISSUE 7, P675-680, October 2002

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A survey of Japanese patients with mitochondrial fatty acid β-oxidation and related disorders as detected from 1985 to 2000


      A clinical survey of Japanese patients with mitochondrial fatty acid β-oxidation and related disorders (FAODs) was performed with questionnaires sent to 187 institutions, where inborn errors of metabolism could be managed in Japan, including a search of related literature published between 1985 and 2000. Sixty-four patients with ten types of FAODs were found. Carnitine palmitoyltransferase 2 deficiency and glutaric aciduria type 2 were most common (17 and 14 patients, respectively). As of 2000, there were no patients with medium-chain acyl-CoA dehydrogenase deficiency, which is common in Caucasians. Age at onset was under 2 years in 38 (59%) of the patients. Eight (13%) patients had neonatal onset. Twenty-one (55%) of the 38 children with an initial attack under 2 years of age had acute encephalopathy or a Reye syndrome-like illness. Half of the patients presented within 2 years of birth died or were handicapped. On the other hand, 19 (79%) of the 24 with onset after 2 years of age had muscle symptoms and 23 (96%) of the 24 grew and developed normally. Though the precise incidence of FAODs in Japan is still unknown, as a consequence of the development of diagnostic procedures the number of FAOD cases being diagnosed appears to have increased. Mass screening for FAODs during the neonatal period will greatly aid in prevention of attacks and related effects.


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        • Bennett M.J
        • Rinaldo P
        • Strauss A.W
        Inborn errors of mitochondrial fatty acid oxidation.
        Crit Rev Clin Lab Sci. 2000; 37: 1-44
        • Roe C.R
        • Coates P.M
        Mitochondrial fatty acid oxidation disorders.
        in: Scriver C.R Beaudet A.L Sly W.S Valle D The molecular and metabolic bases of inherited disease. McGraw-Hill, New York1995: 1501-1533
        • Wanders R.J
        • Vreken P
        • den Boer M.E
        • Wijburg F.A
        • van Gennip A.H
        • Ijlst L
        Disorders of mitochondrial fatty acyl-CoA β-oxidation.
        J Inherit Metab Dis. 1999; 22: 442-487
        • Brivet M
        • Boutron A
        • Slama A
        • Costa C
        • Thuillier L
        • Demaugre F
        • et al.
        Defects in activation and transport of fatty acids.
        J Inherit Metab Dis. 1999; 22: 428-441
        • Roe C.R
        • Millington D.S
        • Maltby D.A
        • Kinnebrew P
        Recognition of medium-chain acyl-CoA dehydrogenase deficiency in asymptomatic siblings of children dying of sudden infant death or Reye-like syndrome.
        J Pediatr. 1986; 108: 13-18
        • Ding J.H
        • Roe C.R
        • Iafolla A.K
        • Chen Y.T
        Medium-chain acyl-coenzyme A dehydrogenase deficiency and sudden infant death.
        N Engl J Med. 1991; 325: 61-62
        • Chang P.F
        • Huang S.F
        • Hwu W.L
        • Hou J.W
        • Ni Y.H
        • Chang M.H
        Metabolic disorders mimicking Reye's syndrome.
        J Formos Med Assoc. 2000; 99: 295-299
        • Bonnet D
        • Martin D
        • De Lonlay P
        • Villain E
        • Jouvet P
        • Rabier D
        • et al.
        Arrhythmias and conduction defects as presenting symptoms of fatty acid oxidation disorders in children.
        Circulation. 1999; 30: 2248-2253
        • Chace D.H
        • Hillman S.L
        • Van Hove J.L
        • Naylor E.W
        Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry.
        Clin Chem. 1997; 43: 2106-2113
        • Treem W.R
        New developments in the pathophysiology, clinical spectrum, and diagnosis of disorders of fatty acid oxidation.
        Curr Opin Pediatr. 2000; 12: 463-468
        • Matsubara Y
        • Narisawa K
        • Miyabayashi S
        • Tada K
        • Coates P.M
        • Bachmann C
        • et al.
        Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency.
        Biochem Biophys Res Commun. 1990; 171: 498-505
        • Koizumi A
        • Nozaki J
        • Ohura T
        • Kayo T
        • Wada Y
        • Nezu J
        • et al.
        Genetic epidemiology of carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency.
        Hum Mol Genet. 1999; 8: 2247-2254
        • Matsubara Y
        • Narisawa K
        • Tada K
        • Ikeda H
        • Yao Y.Q
        • Danks D.M
        • et al.
        Prevalence of K329E mutation in medium-chain acyl-CoA dehydrogenase gene determined from Guthrie cards.
        Lancet. 1991; 338: 552-553
        • Bertrand C
        • Largilliere C
        • Zabot M.T
        • Mathieu M
        • Vianey-Saban C
        Very long chain acyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid oxidation in fibroblasts.
        Biochim Biophys Acta. 1993; 1180: 327-329
        • Aoyama T
        • Uchida Y
        • Kelley R.I
        • Marble M
        • Hofman K
        • Tonsgard J.H
        • et al.
        A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase.
        Biochem Biophys Res Commun. 1993; 191: 1369-1372
        • Yamaguchi S
        • Indo Y
        • Coates P.M
        • Hashimoto T
        • Tanaka K
        Identification of very-long-chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long-chain acyl-CoA dehydrogenase deficiency.
        Pediatr Res. 1993; 34: 111-113
        • Andresen B.S
        • Olpin S
        • Poorthuis B.J
        • Scholte H.R
        • Vianey-Saban C
        • Wanders R
        • et al.
        Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.
        Am J Hum Genet. 1999; 64: 479-494
        • Saudubray J.M
        • Martin D
        • De Lonlay P
        • Touati G
        • Poggi-Travert F
        • Bonnet D
        • et al.
        Recognition and management of fatty acid oxidation defects: a series of 107 patients.
        J Inherit Metab Dis. 1999; 22: 488-502
        • Wilson C.J
        • Champion M.P
        • Collins J.E
        • Clayton P.T
        • Leonard J.V
        Outcome of medium-chain acyl-CoA dehydrogenase deficiency after diagnosis.
        Arch Dis Child. 1999; 80: 459-462
        • Boles R.G
        • Buck E.A
        • Blitzer M.G
        • Platt M.S
        • Cowan T.M
        • Marvin S.K
        • et al.
        Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life.
        J Pediatr. 1998; 132: 924-933
        • Rinaldo P
        • Yoon H.R
        • Yu C
        • Raymond K
        • Tiozzo C
        • Giordano G
        Sudden and unexpected neonatal death: a protocol for the postmortem diagnosis of fatty acid oxidation disorders.
        Semin Perinatol. 1999; 23: 204-210
        • Rashed M.S
        • Buchnall M.P
        • Little D
        • Awad A
        • Jacob M
        • Alamoudi M
        Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles.
        Clin Chem. 1997; 43: 1129-1141
        • Chace D.H
        • DiPerna J.C
        • Naylor E.W
        Laboratory integration and utilization of tandem mass spectrometry in neonatal screening: a model for clinical mass spectrometry in the next millennium.
        Acta Pediatr Suppl. 1999; 432: 45-47