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Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease

  • Pranoot Tanpaiboon
  • Jennifer L. Sloan
  • Patrick F. Callahan
  • Dorothea McAreavey
  • P. Suzanne Hart
  • Uta Lichter-Konecki
  • Dina Zand
  • Charles P. VendittiEmail author
Case Report
Part of the JIMD Reports book series (JIMD, volume 10)

Abstract

Cobalamin C disease (cblC), a form of combined methylmalonic acidemia and hyperhomocysteinemia caused by mutations in the MMACHC gene, may be the most common inborn error of intracellular cobalamin metabolism. The clinical manifestations of cblC disease are diverse and range from intrauterine growth retardation to adult onset neurological disease. The occurrence of structural heart defects appears to be increased in cblC patients and may be related to the function of the MMACHC enzyme during cardiac embryogenesis, a concept supported by the observation that Mmachc is expressed in the bulbis cordis of the developing mouse heart. Here we report an infant who presented with hydrops fetalis, ventricular dysfunction, and echocardiographic evidence of LVNC, a rare congenital cardiomyopathy. Metabolic evaluations, complementation studies, and mutation analysis confirmed the diagnosis of cblC disease. These findings highlight an intrauterine cardiac phenotype that can be displayed in cblC disease in association with nonimmune hydrops.

Keywords

Fabry Disease Pompe Disease Nuchal Translucency Methylmalonic Acidemia Velocardiofacial Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Andersson HC, Marble M, Shapira E (1999) Long term outcome in treated combined methylmalonic academia and homocystinemia. Genet Med 1(4):146–150PubMedCrossRefGoogle Scholar
  2. Baumgartner ER, Wick H, Maurer R et al (1979) Congenital defect in intracellular cobalamin metabolism resulting in homocysteinuria and methylmalonic aciduria I Case report and histopathology. Helv Paediatr Acta 34(5):465–482PubMedGoogle Scholar
  3. Beken S, Cevik A, Turan O et al (2011) A neonatal case of left ventricular noncompaction associated with trisomy 18. Genet Couns 22(2):161–164PubMedGoogle Scholar
  4. Bleyl SB, Mumford BR, Thompson V et al (1997) Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am J Hum Genet 61(4):868–872PubMedCrossRefGoogle Scholar
  5. Blinder JJ, Martinez HR, Craigen WJ et al (2011) Noncompaction of the left ventricular myocardium in a boy with a novel chromosome 8p23.1 deletion. Am J Med Genet A 155A(9):2215–2220PubMedGoogle Scholar
  6. Brandstetter Y, Weinhouse E, Splaingard ML, Tang TT (1990) Cor pulmonale as a complication of methylmalonic acidemia and homocystinuria (Cbl-C type). Am J Med Genet 36(2):167–171PubMedCrossRefGoogle Scholar
  7. Carmel R, Bedros AA, Mace JW, Goodman SI (1980) Congenital methylmalonic aciduria-homocystinuria with megaloblastic anemia: Observations on response to hydroxocobalamin and on the effect of homocysteine and methionine on the deoxyuridine suppression test. Blood 55(4):570–579PubMedGoogle Scholar
  8. Carrillo-Carrasco N, Sloan J, Manoli I et al (2011) A detailed phenotype and long-term outcome of early onset cblC disease. Mol Genet Metab 102(3):246–247Google Scholar
  9. Chang B, Nishizawa T et al (2011) Identification of a novel TPM1 mutation in a family with left ventricular noncompaction and sudden death. Mol Genet Metab 102(2):200–206PubMedCrossRefGoogle Scholar
  10. Chenel C, Wood C, Gourrier E et al (1993) Neonatal hemolytic-uremic syndrome, methylmalonic aciduria and homocystinuria caused by intracellular vitamin B 12 deficiency Value of etiological diagnosis. Arch Fr Pediatr 50(9):749–754PubMedGoogle Scholar
  11. Chin TK, Perloff JK, Williams RG et al (1990) Isolated noncompaction of left ventricular myocardium A study of eight cases. Circulation 82(2):507–513PubMedCrossRefGoogle Scholar
  12. De Bie I, Nizard SD, Mitchell GA (2009) Fetal dilated cardiomyopathy: an unsuspected presentation of methylmalonic aciduria and hyperhomocystinuria, Cbl-C type. Prenat Diagn 29(3):266–270PubMedCrossRefGoogle Scholar
  13. Finsterer J, Stollberger C, Michaela J (2002) Familial left ventricular hypertrabeculation in two blind brothers. Cardiovasc Pathol 11(3):146–148PubMedCrossRefGoogle Scholar
  14. Finsterer J, Stöllberger C, Schubert B (2004) Acquired left ventricular hypertrabeculation/Noncompaction in mitochondriopathy. Cardiology 10 (4) 2:228–230Google Scholar
  15. Finsterer J, Stöllberger C, Blazek G (2006) Neuromuscular implications in left ventricular hypertrabeculation/noncompaction. Int J Cardiol 110(3):288–300PubMedCrossRefGoogle Scholar
  16. Geraghty MT, Perlman EJ, Martin LS et al (1992) Cobalamin C defect associated with hemolytic-uremic syndrome. J Pediatr 120(6):934–937PubMedCrossRefGoogle Scholar
  17. Hannibal L, DiBello PM, Yu M et al (2011) The MMACHC proteome: hallmarks of functional cobalamin deficiency in humans. Mol Genet Metab 103(3):226–239PubMedCrossRefGoogle Scholar
  18. Ichida F (2009) Left ventricular noncompaction. Circ J 73(1):19–26PubMedCrossRefGoogle Scholar
  19. Kanemoto N, Horigome H, Nakayama J et al (2006) Interstitial 1q43-q43 deletion with left ventricular noncompaction myocardium. Eur J Med Genet 49(3):247–253PubMedCrossRefGoogle Scholar
  20. Lerner-Ellis JP, Tirone JC, Pawelek PD et al (2006) Identification of the gene responsible for methylmalonic aciduria and homocystinuria, Cbl-C type. Nat Genet 38(1):93–100PubMedCrossRefGoogle Scholar
  21. Longo D, Fariello G, Dionisi-Vici C et al (2005) MRI and 1H-MRS findings in early-onset cobalamin C/D defect. Neuropediatrics 36(6):366–372PubMedCrossRefGoogle Scholar
  22. Madan S, Madan-Khetarpal S, Park SC et al (2010) Left ventricular non-compaction on MRI in a patient with 22q11.2 distal deletion. Am J Med Genet A 152A(5):1295–1299PubMedCrossRefGoogle Scholar
  23. Martinelli D, Deodato F, Dionisi-Vici C (2010) Cobalamin C defect: natural history, pathophysiology, and treatment. J Inherit Metab Dis 34(1):127–135, Epub 2010 Jul 15PubMedCrossRefGoogle Scholar
  24. Martinez HR, Belmont JW, Craigen WJ, Taylor MD, Jefferies JL (2011) Left ventricular noncompaction in Sotos syndrome. Am J Med Genet A 155A(5):1115–1118PubMedGoogle Scholar
  25. Mc Guire PJ, Parikh A, Diaz GA (2009) Profiling of oxidative stress in patients with inborn errors of metabolism. Mol Genet Metab 98(1–2):173–180PubMedCrossRefGoogle Scholar
  26. McCully KS (1969) Vascular pathology of homocysteinemia:implications for the pathogenesis of arteriosclerosis. Am J Pathol 56(1):111–128PubMedGoogle Scholar
  27. McMahon CJ, Chang AC, Pignatelli RH et al (2005) Left ventricular noncompaction cardiomyopathy in association with trisomy 13. Pediatr Cardiol 26(4):477–479PubMedCrossRefGoogle Scholar
  28. Ogier de Baulny H, Gérard M, Saudubray JM, Zittoun J (1998) Remethylation defects: guidelines for clinical diagnosis and treatment. Eur J Pediatr 157(Suppl 2):S77–S83PubMedCrossRefGoogle Scholar
  29. Pagliarini DJ, Calvo SR, Chang B et al (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134(1):112–123PubMedCrossRefGoogle Scholar
  30. Pauli RM, Scheib-Wixted S, Cripe L et al (1999) Ventricular noncompaction and distal chromosome 5q deletion. Am J Med Genet 85(4):419–423PubMedCrossRefGoogle Scholar
  31. Plesa M, Kim J, Paquette SG et al (2011) Interaction between MMACHC and MMADHC, two human proteins participating in intracellular vitamin B12 metabolism. Mol Genet Metab 102(2):139–148PubMedCrossRefGoogle Scholar
  32. Profitlich LE, Kirmse B, Wasserstein MP et al (2009) High prevalence of structural heart disease in children with Cbl-C-type methylmalonic aciduria and homocystinuria. Mol Genet Metab 98(4):344–348PubMedCrossRefGoogle Scholar
  33. Pupavac M, Garcia MA, Rosenblatt DS, Jerome-Majewska LA (2011) Expression of Mmachc and Mmadhc during mouse organogenesis. Mol Genet Metab 103(4):401–405PubMedCrossRefGoogle Scholar
  34. Richard E, Jorge-Finnigan A, Garcia-Villoria J et al (2009) Genetic and cellular studies of oxidative stress in methylmalonic aciduria (MMA) cobalamin deficiency type c (cblC) with homocystinuria (MMACHC). Hum Mutat 30(11):1158–1566CrossRefGoogle Scholar
  35. Richards A, Mao CY, Dobson NR (2009) Left ventricular non compaction: A rare cause of hydrops fetalis. Pediatr Cardiol 30(7):985–988, Epub 2009 Jun 9PubMedCrossRefGoogle Scholar
  36. Rosenblatt DS, Aspler AL, Shevell MI, Pletcher BA, Fenton WA, Seashore MR (1997) Clinical heterogeneity and prognosis in combined methylmalonic aciduria and homocystinuria (cblC). J Inherit Metab Dis 20(4):528–538PubMedCrossRefGoogle Scholar
  37. Sasse-Klaassen S, Probst S, Gerull B et al (2004) Novel gene locus for autosomal dominant left ventricular noncompaction maps to chromosome 11p15. Circulation 109(22):2720–2723, Epub 2004 Jun 1PubMedCrossRefGoogle Scholar
  38. Sellars EA, Zimmerman SL, Smolarek T et al (2011) Ventricular noncompaction and absent thumbs in a newborn with tetrasomy 5q35.2-5q3.5: An association with Hunter-McAlpine syndrome? Am J Med Genet A 155A(6):1409–1413PubMedGoogle Scholar
  39. Stöllberger C, Finsterer J, Valentin A et al (1999) Isolated left ventricular abnormal trabeculation in adults is associated with neuromuscular disorders. Clin Cardiol 22(2):119–123PubMedCrossRefGoogle Scholar
  40. Stöllberger C, Finsterer J, Voigtlander T, Slany J (2003) Is left ventricular hypertrabeculation/noncompaction a cardiac manifestation of Fabry’s disease? Z Kardiol 92(11):966–999PubMedCrossRefGoogle Scholar
  41. Tang S, Batra A, Zhang Y et al (2010) Left ventricular noncompaction is associated with mutations in the mitochondrial genome. Mitochondrion 10(4):350–357PubMedCrossRefGoogle Scholar
  42. Thienpont B, Mertens L, Buyse G et al (2007) Left-ventricular non-compaction in a patient with monosomy 1p36. Eur J Med Genet 50(3):233–236PubMedCrossRefGoogle Scholar
  43. Wang JC, Dang L, Mondal TK, Khan A (2007) Prenatally diagnosed mosaic trisomy 22 in a fetus with left ventricular non-compaction cardiomyopathy. Am J Med Genet A143A(22):2744–2746CrossRefGoogle Scholar
  44. Xing Y, Ichida F, Matsuoka T et al (2006) Genetic analysis in patients with left ventricular noncompaction and evidence for genetic heterogeneity. Mol Genet Metab 88(1):71–77PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Pranoot Tanpaiboon
    • 1
  • Jennifer L. Sloan
    • 2
  • Patrick F. Callahan
    • 3
  • Dorothea McAreavey
    • 4
  • P. Suzanne Hart
    • 5
  • Uta Lichter-Konecki
    • 1
  • Dina Zand
    • 1
  • Charles P. Venditti
    • 2
    Email author
  1. 1.Division of Genetics and MetabolismChildren’s National Medical CenterWashington, DCUSA
  2. 2.Organic Acid Research Section, Genetics and Molecular Biology BranchNational Human Genome Research Institute, National Institutes of HealthBethesdaUSA
  3. 3.Child Cardiology AssociatesFairfaxUSA
  4. 4.Critical Care Medicine DepartmentNational Institutes of Health (NIH)BethesdaUSA
  5. 5.Office of the Clinical Director, Medical Genetics BranchNational Human Genome Research Institute (NHGRI), National Institutes of Health (NIH)BethesdaUSA

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