European Journal of Pediatrics

, Volume 152, Issue 5, pp 428–432 | Cite as

An unusual patient with the neonatal Marfan phenotype and mitochondrial complex I deficiency

  • J. Christodoulou
  • R. Petrova-Benedict
  • B. H. Robinson
  • V. Jay
  • J. T. R. Clarke
Medical Genetics


We report the case of a 16-month-old male with the neonatal appearance of Marfan syndrome (NMS), with dolichocephaly, a long midface, deep-set eyes, arachnodactyly, dislocated lenses and carciovascular abnormalities. The presence of persistent lactic acidosis led to studies which disclosed mitochondrial complex I deficiency. We speculate that this unusual association may be due to the combination of an inherited mutation affecting complex I activity along with a de novo mutation disrupting the corresponding locus and an adjacent NMS locus on the homologous autosome. The possibility that the phenotype observed in this patient is directly due to the mitochondrial defect cannot be excluded.

Key words

Marfan NADH-coenzyme Q reductase Lactic acidosis Respiratory chain Mitochondrial myopathy 



neonatal Marfan syndrome


mitochondrial DNA


mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes


myoclonus epilepsy, ragged red fibres


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  1. 1.
    Bernsen PLJA, Gabreëls FJM, Ruitenbeek W, Sengers RCA, Stadhouders AM, Renier WO (1991) Successful treatment of pure myopathy, associated with complex I deficiency, with riboflavin and carnitine. Arch Neurol 48:334–338PubMedGoogle Scholar
  2. 2.
    Buntinx IM, Willems PJ, Spitaels SE, Van Reempst P, De Paepe A, Dumon JE (1991) Neonatal Marfan syndrome with congenital arachnodactyly, flexion contractures, and severe cardiac valve insufficiency. J Med Genet 28:267–273PubMedGoogle Scholar
  3. 3.
    Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, Puffenberger EG, et al (1991) Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 352:337–339PubMedGoogle Scholar
  4. 4.
    Fujii T, Ito M, Okuno T, Mutoh K, Nishikomori R, Mikawa H (1990) Complex I (reduced nicotinamide-adenine dinucleotide-coenzyme Q reductase) deficiency in two patients with probable Leigh syndrome. J Pediatr 116:84–87PubMedGoogle Scholar
  5. 5.
    Goodman SI, Markey SP (1981) Diagnosis of organic acidemias by gas chromatography/mass spectrometry, Alan R Liss, New York, pp 1–43Google Scholar
  6. 6.
    Goto YI, Nonaka I, Horai S (1990) A mutation in the tRNALeu(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653PubMedGoogle Scholar
  7. 7.
    Gross DM, Robinson LK, Smith LT, Glass N, Rosenberg H, Duvic M (1989) Severe perinatal Marfan syndrome. Pediatrics 84:83–89PubMedGoogle Scholar
  8. 8.
    Kainulainen K, Pulkkinen L, Savolainen A, Kaitila I, Peltonen L (1990) Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med 323:935–939PubMedGoogle Scholar
  9. 9.
    Kobayashi M, Morishita H, Sugiyama N, Yokochi K, Nakano M, Wada Y, Hotta Y, et al (1987) Two cases of NADH-coenzyme Q reductase deficiency: relationship to MELAS syndrome. J Pediatr 110:223–227PubMedGoogle Scholar
  10. 10.
    Lee B, Godfrey M, Vitale E, Hori H, Mattei M-G, Sarfarazi M, Tsipouras P, et al (1991) Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature 352:330–334PubMedGoogle Scholar
  11. 11.
    McKusick VA (1990) Mendelian inheritance in man. Johns Hopkins University Press, Balitmore, pp 599–601Google Scholar
  12. 12.
    Moreadith RW, Batshaw ML, Ohnishi T, Kerr D, Knox B, Jackson D, Hruban R, et al (1984) Deficiency of the iron sulfer clusters of mitochondrial reduced nicotinamide adenine dinucleotide-ubiquinone oxidoreductase (Complex I) in an infant with congenital lactic acidosis. J Clin Invest 74:685–697PubMedGoogle Scholar
  13. 13.
    Morgan-Hughes JA, Darveniza P, Landon DN, Land JM, Clark JB (1979) A mitochondrial myopathy with a deficiency of respiratory chain NADH-CoQ reductase activity. J Neurol Sci 43:27–46PubMedGoogle Scholar
  14. 14.
    Morgan-Hughes JA, Hayes DJ, Clark JB, Landon DN, Swash M, Stark RJ, Rudge P (1982) Mitochondrial encephalomyopathies. Biochemical studies in two cases revealing defects in the respiratory chain. Brain 105:553–582PubMedGoogle Scholar
  15. 15.
    Morgan-Hughes JA, Hayes DJ, Cooper M, Clark JB (1985) Mitochondrial myopathies: deficiencies localized to complex I and complex III of the mitochondrial respiratory chain. Biochem Soc Trans 13:648–650PubMedGoogle Scholar
  16. 16.
    Morse RP, Rockenmacher S, Pyeritz RE, Sanders SP, Bieber FR, Lin A, MacLeod P, Hall B, Graham JM Jr (1990) Diagnosis and management of infantile Marfan syndrome. Pediatrics 86:888–895PubMedGoogle Scholar
  17. 17.
    Pulkkinen L, Kainulainen K, Krusius T, Mäkinen P, Schollin J, Gustavsson K-H, Peltonen L (1990) Deficient expression of the gene coding for decorin in a lethal form of Marfan syndrome. J Biol Chem 265:11780–11785Google Scholar
  18. 18.
    Robinson BH, Taylor J, Sherwood WG (1980) The genetic heterogeneity of lactic acidosis: occurrence of recognizable inborn errors of metabolism in a pediatric population with lactic acidosis. Pediatr Res 14:956–962PubMedGoogle Scholar
  19. 19.
    Robinson BH, De Meirleir L, Glerum M, Sherwood G, Becker L (1987) Clinical presentation of mitochondrial respiratory chain defects in NADH-coenzyme Q reductase and cytochrome oxidase: clues to pathogenesis of Leigh disease. J Pediatr 110: 216–222PubMedGoogle Scholar
  20. 20.
    Robinson BH, Glerum DM, Chow W, Petrova BR, Lightowlers R, Capaldi (1990) The use of skin fibroblast cultures in the detection of respiratory chain defects in patients with lactic acidemia. Pediatr Res 84:549–555Google Scholar
  21. 21.
    Robinson BH, Chow W, Petrova-Benedict R, Clarke JTR, Allen MI van, Becker LE, Boulton JE, Ragan I (1992) Fatal combined defects in mitochondrial multienzyme complexes in two siblings. Eur J Pediatr 151:347–352PubMedGoogle Scholar
  22. 22.
    Shoffner JM, Lott MT, Lezza AMS, Seibel P, Ballinger SW, Wallace DC (1990) Myoclonic epilepsy and ragged-red fibre disease (MERRF) is associated with a mitochondrial tRNALys mutation. Cell 61:931–937PubMedGoogle Scholar
  23. 23.
    Smith I, Ersser RS (1975) Thin layer chromatography. In: Smith I, Seakins JWT (eds) Chromatographic and electrophoretic techniques, Vol. 1. William Heinemann Medical Books Ltd. London, pp 18–55Google Scholar
  24. 24.
    Tsipouras P, Sarfarazi M, Devi A, Weiffenbach B, Boxer M (1991) Marfan syndrome is closely linked to a marker on chromosome 15q1.5→q2.1. Proc Natl Acad Sci USA 88:4486–4488PubMedGoogle Scholar
  25. 25.
    Wallace DC (1991) Mitochondrial genes and neuromuscular diseases. In: McHugh PR, McKusick VA (eds) Genes, brain and behaviour. Raven Press Ltd, New York, pp 101–120Google Scholar
  26. 26.
    Wallace DC, Singh G, Lott MT, Hodge JA, Schurr RG, Lezza MS, Elsas LJ, et al (1988) Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 242: 1427–1430PubMedGoogle Scholar
  27. 27.
    Zeviani M, Bresolin N, Gellera C, Bordoni A, Pannacci M, Amati P, Moggio M, et al (1990) Nucleus-driven multiple largescale deletions of the human mitochondrial genome: a new autosomal dominant disease. Am J Hum Genet 47:904–914PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • J. Christodoulou
    • 1
  • R. Petrova-Benedict
    • 1
  • B. H. Robinson
    • 1
  • V. Jay
    • 2
  • J. T. R. Clarke
    • 1
  1. 1.Division of Clinical GeneticsHospital for Sick ChildrenTorontoCanada
  2. 2.Division of PathologyHospital for Sick ChildrenTorontoCanada

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