Homozygosity for a severe novel medium-chain acyl-CoA dehydrogenase (MCAD) mutation IVS3-1G > C that leads to introduction of a premature termination codon by complete missplicing of the MCAD mRNA and is associated with phenotypic diversity ranging from sudden neonatal death to asymptomatic status

Molecular Genetics and Metabolism

Volumn 82, Issue 2, 2004, Pages 121-129

  Korman, Stanley H ^a   Gutman, Alisa ^a   Brooks, Rivka ^a   Sinnathamby, Thayline ^b,c   Gregersen, Niels ^b   Andresen, Brage S ^b,c  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^b AARHUS UNIVERSITY HOSPITAL   (Denmark)

^c AARHUS UNIVERSITY   (Denmark)

Author keywords

Ethylmalonic aciduria; Genotype phenotype correlation; Medium chain acyl CoA dehydrogenase; Short chain acyl CoA dehydrogenase; Splice mutation; Sudden infant death

Indexed keywords

ACYL COENZYME A DEHYDROGENASE; ACYLCARNITINE;

ARAB; ARTICLE; CASE REPORT; CLINICAL FEATURE; CORRELATION ANALYSIS; DISEASE ASSOCIATION; ENZYME ACTIVITY; FEMALE; GENE FUNCTION; GENE IDENTIFICATION; GENE MUTATION; GENETIC CODE; GENOTYPE; HOMOZYGOSITY; HUMAN; MALE; MOLECULAR DYNAMICS; PHENOTYPE; PRIORITY JOURNAL; RNA SPLICING; STOP CODON; SUDDEN INFANT DEATH SYNDROME;

ACYL-COA DEHYDROGENASE; ADULT; ALTERNATIVE SPLICING; ARABS; BASE SEQUENCE; CARNITINE; CHILD; CODON, NONSENSE; FEMALE; HOMOZYGOTE; HUMANS; INFANT, NEWBORN; MALE; MUTATION; OXIDATION-REDUCTION; PEDIGREE; PHENOTYPE; RNA, MESSENGER; SUDDEN INFANT DEATH;

EID: 2542420892     PISSN: 10967192     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ymgme.2004.03.002     Document Type: Article

References (33)

1. Iafolla A.K., Thompson R.J. Jr., Roe C.R. Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children. J. Pediatr. 124:1994;409-415
2. Roe C.R., Ding J. Mitochondrial fatty acid oxidation disorders. Scriver C.R., Beaudet A.L., Sly W.S., Valle D. The Metabolic & Molecular Bases of Inherited Disease. 2001;2297-2326 McGraw-Hill, New York
3. Andresen B.S., Bross P., Udvari S., Kirk J., Gray G., Kmoch S., Chamoles N., Knudsen I., Winter V., Wilcken B., Yokota I., Hart K., Packman S., Harpey J.P., Saudubray J.M., Hale D.E., Bolund L., Kolvraa S., Gregersen N. The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in compound heterozygous patients: is there correlation between genotype and phenotype? Hum. Mol. Genet. 6:1997;695-707
4. Andresen B.S., Dobrowolski S.F., O'Reilly L., Muenzer J., McCandless S.E., Frazier D.M., Udvari S., Bross P., Knudsen I., Banas R., Chace D.H., Engel P., Naylor E.W., Gregersen N. Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency. Am. J. Hum. Genet. 68:2001;1408-1418
5. Corydon M.J., Vockley J., Rinaldo P., Rhead W.J., Kjeldsen M., Winter V., Riggs C., Babovic-Vuksanovic D., Smeitink J., De Jong J., Levy H., Sewell A.C., Roe C., Matern D., Dasouki M., Gregersen N. Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency. Pediatr. Res. 49:2001;18-23
6. Johnson A.W., Mills K., Clayton P.T. The use of automated electrospray ionization tandem MS for the diagnosis of inborn errors of metabolism from dried blood spots. Biochem. Soc. Trans. 24:1996;932-938
7. 3H]myristic acids for the detection of defects of fatty acid oxidation in intact cultured fibroblasts. J. Inherit. Metab. Dis. 13:1990;58-68
8. Brivet M., Slama A., Saudubray J.M., Legrand A., Lemonnier A. Rapid diagnosis of long chain and medium chain fatty acid oxidation disorders using lymphocytes. Ann. Clin. Biochem. 32(Pt. 2):1995;154-159
9. 3H]oleic acid. J. Inherit. Metab. Dis. 20:1997;415-419
10. Corydon M.J., Andresen B.S., Bross P., Kjeldsen M., Andreasen P.H., Eiberg H., Kolvraa S., Gregersen N. Structural organization of the human short-chain acyl-CoA dehydrogenase gene. Mamm. Genome. 8:1997;922-926
11. Zhang Z.F., Kelly D.P., Kim J.J., Zhou Y.Q., Ogden M.L., Whelan A.J., Strauss A.W. Structural organization and regulatory regions of the human medium-chain acyl-CoA dehydrogenase gene. Biochemistry. 31:1992;81-89
12. Van Hove J.L., Zhang W., Kahler S.G., Roe C.R., Chen Y.T., Terada N., Chace D.H., Iafolla A.K., Ding J.H., Millington D.S. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood. Am. J. Hum. Genet. 52:1993;958-966
13. Clayton P.T., Doig M., Ghafari S., Meaney C., Taylor C., Leonard J.V., Morris M., Johnson A.W. Screening for medium chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry. Arch. Dis. Child. 79:1998;109-115
14. Ozand P.T. Diagnosis of inborn errors of metabolism by tandem mass spectrometry. Ann. Saudi Med. 18:1998;234-239
15. Gregersen N., Winter V., Curtis D., Deufel T., Mack M., Hendrickx J., Willems P.J., Ponzone A., Parrella T., Ponzone R., Ding J.H., Zhang W., Chen Y.T., Kahler S., Roe C.R., Kolvraa S., Schneiderman K., Andresen B.S., Bross P., Bolund L. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: the prevalent mutation G985 (K304E) is subject to a strong founder effect from northwestern Europe. Hum. Hered. 43:1993;342-350
16. Tanaka K., Gregersen N., Ribes A., Kim J., Kolvraa S., Winter V., Eiberg H., Martinez G., Deufel T., Leifert B., Santer R., Francois B., Pronicka E., Laszlo A., Kmoch S., Kremensky I., Kalaydjicva L., Ozalp I., Ito M. 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. 41:1997;201-209
17. Naylor E.W., Chace D.H. Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid, organic acid, and amino acid metabolism. J. Child Neurol. 14(Suppl. 1):1999;S4-S8
18. Rashed M.S., Bucknall M.P., Little D., Awad A., Jacob M., Alamoudi M., Alwattar M., Ozand P.T. 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. 43:1997;1129-1141
19. Kambouris M., Rahbeeni Z., Meyer B.F., Al-Yamani E.A., Ozand P.T., Rashed M. Mutation screening of the MCAD gene in patients with biochemical medium-chain fatty acid oxidation defects (MCFAOD). Am. J. Hum. Genet. 61(Suppl. 6):1997;A254
20. Wilcken B., Carpenter K.H., Hammond J. Neonatal symptoms in medium chain acyl coenzyme A dehydrogenase deficiency. Arch. Dis. Child. 69:1993;292-294
21. Catzeflis C., Bachmann C., Hale D.E., Coates P.M., Wiesmann U., Colombo J.P., Joris F., Deleze G. Early diagnosis and treatment of neonatal medium-chain acyl-CoA dehydrogenase deficiency: report of two siblings. Eur. J. Pediatr. 149:1990;577-581
22. Leung K.C., Hammond J.W., Chabra S., Carpenter K.H., Potter M., Wilcken B. A fatal neonatal case of medium-chain acyl-coenzyme A dehydrogenase deficiency with homozygous A. → G985 transition J. Pediatr. 121:1992;965-968
23. Brackett J.C., Sims H.F., Steiner R.D., Nunge M., Zimmerman E.M., deMartinville B., Rinaldo P., Slaugh R., Strauss A.W. A novel mutation in medium chain acyl-CoA dehydrogenase causes sudden neonatal death. J. Clin. Invest. 94:1994;1477-1483
24. Kirk J.M., Laing I.A., Smith N., Uttley W.S. Neonatal presentation of medium-chain acyl-CoA dehydrogenase deficiency in two families. J. Inherit. Metab. Dis. 19:1996;370-371
25. Andresen B.S., Bross P., Jensen T.G., Winter V., Knudsen I., Kolvraa S., Jensen U.B., Bolund L., Duran M., Kim J.J., Curtis D., Divry P., Vianey-Saban C., Gregersen N. A rare disease-associated mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene changes a conserved arginine, previously shown to be functionally essential in short-chain acyl-CoA dehydrogenase (SCAD). Am. J. Hum. Genet. 53:1993;730-739
26. Andresen B.S., Olpin S., Poorthuis B.J., Scholte H.R., Vianey-Saban C., Wanders R., Ijlst L., Morris A., Pourfarzam M., Bartlett K., Baumgartner E.R., deKlerk J.B., Schroeder L.D., Corydon T.J., Lund H., Winter V., Bross P., Bolund L., Gregersen N. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. Am. J. Hum. Genet. 64:1999;479-494
27. Duran M., Hofkamp M., Rhead W.J., Saudubray J.M., Wadman S.K. Sudden child death and 'healthy' affected family members with medium-chain acyl-coenzyme A dehydrogenase deficiency. Pediatrics. 78:1986;1052-1057
28. 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 syndromes. J. Pediatr. 108:1986;13-18
29. Bross P., Andresen B.S., Winter V., Krautle F., Jensen T.G., Nandy A., Kolvraa S., Ghisla S., Bolund L., Gregersen N. Co-overexpression of bacterial GroESL chaperonins partly overcomes non-productive folding and tetramer assembly of E. coli-expressed human medium-chain acyl-CoA dehydrogenase (MCAD) carrying the prevalent disease-causing K304E mutation. Biochim. Biophys. Acta. 1182:1993;264-274
30. Bross P., Jespersen C., Jensen T.G., Andresen B.S., Kristensen M.J., Winter V., Nandy A., Krautle F., Ghisla S., Bolund L., Kim J.J.P., Gregersen N. Effects of two mutations detected in medium chain acyl-CoA dehydrogenase (MCAD)-deficient patients on folding, oligomer assembly, and stability of MCAD enzyme. J. Biol. Chem. 270:1995;10284-10290
31. Dipple K.M., McCabe E.R. Modifier genes convert "simple" Mendelian disorders to complex traits. Mol. Genet. Metab. 71:2000;43-50
32. Dipple K.M., McCabe E.R. Phenotypes of patients with "simple" Mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics. Am. J. Hum. Genet. 66:2000;1729-1735
33. Dipple K.M., Phelan J.K., McCabe E.R. Consequences of complexity within biological networks: robustness and health, or vulnerability and disease. Mol. Genet. Metab. 74:2001;45-50