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The clinical manifestation of MCAD deficiency: challenges towards adulthood in the screened population

  • Fatty Acid Oxidation
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common fatty acid oxidation disorder. Typically, undiagnosed individuals are asymptomatic until an episode of increased energy demand and fasting occurs, resulting in metabolic derangement. Phenotypic heterogeneity has been increasingly realized, with reports of both neonates and adults manifesting with life-threatening symptoms including encephalopathy, rhabdomyolysis, and cardiac failure. If diagnosed presymptomatically, outcome is favorable basically by avoidance of fasting. Early detection by newborn screening (NBS) has significantly reduced the incidence of severe adverse events including deaths. In this manuscript we focus on the natural course of the disease in both children and adults. Although NBS for MCADD has been successfully established, continuing efforts need to be made to avoid acute crises and deterioration of outcome in screened patients entering adolescence and adulthood.

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Abbreviations

ACADM :

Medium-chain acyl-CoA dehydrogenase encoding gene

CK:

Creatine kinase

MCAD:

Medium-chain acyl-CoA dehydrogenase

MCADD:

MCAD deficiency

NBS:

Newborn screening

TMS:

Tandem mass spectrometry

References

  • Andresen BS, Dobrowolski SF, O'Reilly L et al (2001) 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 68:1408–1418

    Article  CAS  PubMed  Google Scholar 

  • Boles RG, Boesel C, Rinaldo P (1996) Sudden death beyond SIDS. Pediatr Pathol Lab Med 16:691–693

    Article  CAS  PubMed  Google Scholar 

  • Chace DH, Kalas TA, Naylor EW (2003) Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem 49:1797–1817

    Article  CAS  PubMed  Google Scholar 

  • Derks TG, Duran M, Waterham HR, Reijngoud DJ, Ten Kate LP, Smit GP (2005) The difference between observed and expected prevalence of MCAD deficiency in the Netherlands: a genetic epidemiological study. Eur J Hum Genet 13:947–952

    Article  CAS  PubMed  Google Scholar 

  • Derks TG, Reijngoud DJ, Waterham HR et al (2006) The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: clinical presentation and outcome. J Pediatr 148:665–670

    Article  CAS  PubMed  Google Scholar 

  • Duran M, Hofkamp M, Rhead WJ, Saudubray JM, Wadman SK (1986) Sudden child death and ‘healthy’ affected family members with medium-chain acyl-coenzyme A dehydrogenase deficiency. Pediatrics 78:1052–1057

    CAS  PubMed  Google Scholar 

  • Feillet F, Steinmann G, Vianey-Saban C et al (2003) Adult presentation of MCAD deficiency revealed by coma and severe arrythmias. Intensive Care Med 29:1594–1597

    Article  CAS  PubMed  Google Scholar 

  • Felig P, Lynch V (1970) Starvation in human pregnancy: hypoglycemia, hypoinsulinemia, and hyperketonemia. Science 170:990–992

    Article  CAS  PubMed  Google Scholar 

  • Finocchiaro G, Ito M, Tanaka K (1987) Purification and properties of short chain acyl-CoA, medium chain acyl-CoA, and isovaleryl-CoA dehydrogenases from human liver. J Biol Chem 262:7982–7989

    CAS  PubMed  Google Scholar 

  • Gregersen N, Lauritzen R, Rasmussen K (1976) Suberylglycine excretion in the urine from a patient with dicarboxylic aciduria. Clin Chim Acta 70:417–425

    Article  CAS  PubMed  Google Scholar 

  • Gregersen N, Andresen BS, Bross P (2000) Prevalent mutations in fatty acid oxidation disorders: diagnostic considerations. Eur J Pediatr 159(Suppl 3):213–218

    Article  Google Scholar 

  • Grosse SD, Khoury MJ, Greene CL, Crider KS, Pollitt RJ (2006) The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: an update. Genet Med 8:205–212

    Article  CAS  PubMed  Google Scholar 

  • Hoffmann GF, von Kries R, Klose D et al (2004) Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany. Eur J Pediatr 163:76–80

    Article  CAS  PubMed  Google Scholar 

  • Horowitz JF, Leone TC, Feng W, Kelly DP, Klein S (2000) Effect of endurance training on lipid metabolism in women: a potential role for PPARα in the metabolic response to training. Am J Physiol Endocrinol Metab 279:348–355

    Google Scholar 

  • Horvath GA, Davidson AG, Stockler-Ipsiroglu SG et al (2008) Newborn screening for MCAD deficiency: experience of the first three years in British Columbia, Canada. Can J Public Health 99:276–280

    PubMed  Google Scholar 

  • Howat AJ, Bennett MJ, Variend S, Shaw L (1984) Deficiency of medium chain fatty acylcoenzyme A dehydrogenase presenting as the sudden infant death syndrome. Br Med J (Clin Res Ed) 288:976

    Article  CAS  Google Scholar 

  • Hsu HW, Zytkovicz TH, Comeau AM et al (2008) Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening. Pediatrics 121:1108–1114

    Article  Google Scholar 

  • Iafolla AK, Thompson RJ Jr, Roe CR (1994) Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children. J Pediatr 124:409–415

    Article  CAS  PubMed  Google Scholar 

  • Joy P, Black C, Rocca A, Haas M, Wilcken B (2009) Neuropsychological functioning in children with medium chain acyl coenzyme a dehydrogenase deficiency (MCADD): the impact of early diagnosis and screening on outcome. Child Neuropsychol 15:8–20

    Article  PubMed  Google Scholar 

  • Khalid JM, Oerton J, Cortina-Borja M et al (2008) Ethnicity of children with homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency: findings from screening approximately 1.1 million newborn infants. J Med Screen 15:112–117

    Article  CAS  PubMed  Google Scholar 

  • Kølvraa S, Gregersen N, Christensen E, Hobolth N (1982) In vitro fibroblast studies in a patient with C6-C10-dicarboxylic aciduria: evidence for a defect in general acyl-CoA dehydrogenase. Clin Chim Acta 126:53–67

    Article  CAS  PubMed  Google Scholar 

  • Leonard JV, Dezateux C (2009) Newborn screening for medium chain acyl CoA dehydrogenase deficiency. Arch Dis Child 94:235–238

    Article  CAS  PubMed  Google Scholar 

  • Maier EM, Liebl B, Roschinger W et al (2005) Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Hum Mutat 25:443–452

    Article  CAS  PubMed  Google Scholar 

  • Mayell SJ, Edwards L, Reynolds FE, Chakrapani AB (2007) Late presentation of medium-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis 30:104

    Article  CAS  PubMed  Google Scholar 

  • Nennstiel-Ratzel U, Arenz S, Maier EM et al (2005) Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deficiency homozygous for c.985A>G identified by neonatal screening. Mol Genet Metab 85:157–159

    Article  CAS  PubMed  Google Scholar 

  • Nichols MJ, Saavedra-Matiz CA, Pass KA, Caggana M (2008) Novel mutations causing medium chain acyl-CoA dehydrogenase deficiency: under-representation of the common c.985A>G mutation in the New York state population. Am J Med Genet A 146A:610–619

    Article  CAS  PubMed  Google Scholar 

  • Norman R, Haas M, Chaplin M, Joy P, Wilcken B (2009) Economic evaluation of tandem mass spectrometry newborn screening in Australia. Pediatrics 123:451–457

    Article  PubMed  Google Scholar 

  • Pollitt RJ, Leonard JV (1998) Prospective surveillance study of medium chain acyl-CoA dehydrogenase deficiency in the UK. Arch Dis Child 79:116–119

    Article  CAS  PubMed  Google Scholar 

  • Pourfarzam M, Morris A, Appleton M, Craft A, Bartlett K (2001) Neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency. Lancet 358:1063–1064

    Article  CAS  PubMed  Google Scholar 

  • Raymond K, Bale AE, Barnes CA, Rinaldo P (1999) Medium-chain acyl-CoA dehydrogenase deficiency: sudden and unexpected death of a 45 year old woman. Genet Med 1:293–294

    Article  CAS  PubMed  Google Scholar 

  • Rhead WJ (2006) Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: a global perspective. J Inherit Metab Dis 29:370–377

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez NR, Di Marco NM, Langley S (2009) American College of Sports Medicine position stand. Nutrition and athletic performance. Med Sci Sports Exerc 41:709–731

    Article  PubMed  Google Scholar 

  • Ruitenbeek W, Poels PJ, Turnbull DM et al (1995) Rhabdomyolysis and acute encephalopathy in late onset medium chain acyl-CoA dehydrogenase deficiency. J Neurol Neurosurg Psychiatry 58:209–214

    Article  CAS  PubMed  Google Scholar 

  • Santos L, Patterson A, Moreea SM, Lippiatt CM, Walter J, Henderson M (2007) Acute liver failure in pregnancy associated with maternal MCAD deficiency. J Inherit Metab Dis 30:103

    Article  CAS  PubMed  Google Scholar 

  • Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF (2003) Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics 111:1399–1406

    Article  PubMed  Google Scholar 

  • Stanley CA, Hale DE, Coates PM et al (1983) Medium-chain acyl-CoA dehydrogenase deficiency in children with non-ketotic hypoglycemia and low carnitine levels. Pediatr Res 17:877–884

    CAS  PubMed  Google Scholar 

  • Stolle M, Sack PM, Thomasius R (2009) Binge drinking in childhood and adolescence: epidemiology, consequences, and interventions. Dtsch Arztebl Int 106:323–328

    PubMed  Google Scholar 

  • Touma EH, Charpentier C (1992) Medium chain acyl-CoA dehydrogenase deficiency. Arch Dis Child 67:142–145

    Article  CAS  PubMed  Google Scholar 

  • Waddell L, Wiley V, Carpenter K et al (2006) Medium-chain acyl-CoA dehydrogenase deficiency: genotype-biochemical phenotype correlations. Mol Genet Metab 87:32–39

    Article  CAS  PubMed  Google Scholar 

  • Wang SY, Kannan S, Shay D, Segal S, Datta S, Tsen L (2002) Anesthetic considerations for a patient with compound heterozygous medium-chain Acyl-CoA dehydrogenase deficiency. Anesth Analg 94:1595–1597

    Article  PubMed  Google Scholar 

  • Wilcken B (2008) More on medium-chain acyl-coenzyme a dehydrogenase deficiency in a neonate. N Engl J Med 358:647

    CAS  PubMed  Google Scholar 

  • Wilcken B, Hammond J, Silink M (1994) Morbidity and mortality in medium chain acyl coenzyme A dehydrogenase deficiency. Arch Dis Child 70:410–412

    Article  CAS  PubMed  Google Scholar 

  • Wilcken B, Haas M, Joy P et al (2007) Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study. Lancet 369:37–42

    Article  CAS  PubMed  Google Scholar 

  • Wilcken B, Haas M, Joy P et al (2009) Expanded newborn screening: outcome in screened and unscreened patients at age 6 years. Pediatrics 124:241–248

    Article  Google Scholar 

  • Wilhelm GW (2006) Sudden death in a young woman from medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. J Emerg Med 30:291–294

    Article  PubMed  Google Scholar 

  • Wilson CJ, Champion MP, Collins JE, Clayton PT, Leonard JV (1999) Outcome of medium chain acyl-CoA dehydrogenase deficiency after diagnosis. Arch Dis Child 80:459–462

    Article  CAS  PubMed  Google Scholar 

  • Zschocke J, Schulze A, Lindner M et al (2001) Molecular and functional characterisation of mild MCAD deficiency. Hum Genet 108:404–408

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Dr. von Hauner Children’s Hospital, Children’s Research Center, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337, Munich, Germany

    Ulrich A. Schatz & Regina Ensenauer

Authors
  1. Ulrich A. Schatz
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  2. Regina Ensenauer
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Corresponding author

Correspondence to Regina Ensenauer.

Additional information

Communicated by: Verena Peters

References to electronic databases: OMIM disorder accession number: http://www.ncbi.nlm.nih.gov/omim

HUGO gene name: http://www.genenames.org/index.html

Enzyme commission: http://www.chem.qmul.ac.uk/iubmb/enzyme/

Competing interest: None declared.

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Schatz, U.A., Ensenauer, R. The clinical manifestation of MCAD deficiency: challenges towards adulthood in the screened population. J Inherit Metab Dis 33, 513–520 (2010). https://doi.org/10.1007/s10545-010-9115-5

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  • DOI: https://doi.org/10.1007/s10545-010-9115-5

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