Skip to main content
SpringerLink
Log in

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

  • Case Report
  • Chapter
  • First Online:
JIMD Reports - Volume 10

Part of the book series: JIMD Reports ((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.

Competing interests: None declared

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andersson HC, Marble M, Shapira E (1999) Long term outcome in treated combined methylmalonic academia and homocystinemia. Genet Med 1(4):146–150

    Article  PubMed  CAS  Google Scholar 

  • 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):465–482

    PubMed  CAS  Google Scholar 

  • Beken S, Cevik A, Turan O et al (2011) A neonatal case of left ventricular noncompaction associated with trisomy 18. Genet Couns 22(2):161–164

    PubMed  CAS  Google Scholar 

  • 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):868–872

    Article  PubMed  CAS  Google Scholar 

  • 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):2215–2220

    PubMed  Google Scholar 

  • 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):167–171

    Article  PubMed  CAS  Google Scholar 

  • 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):570–579

    PubMed  CAS  Google Scholar 

  • 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):246–247

    Google Scholar 

  • 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):200–206

    Article  PubMed  Google Scholar 

  • 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):749–754

    PubMed  CAS  Google Scholar 

  • Chin TK, Perloff JK, Williams RG et al (1990) Isolated noncompaction of left ventricular myocardium A study of eight cases. Circulation 82(2):507–513

    Article  PubMed  CAS  Google Scholar 

  • 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):266–270

    Article  PubMed  Google Scholar 

  • Finsterer J, Stollberger C, Michaela J (2002) Familial left ventricular hypertrabeculation in two blind brothers. Cardiovasc Pathol 11(3):146–148

    Article  PubMed  Google Scholar 

  • Finsterer J, Stöllberger C, Schubert B (2004) Acquired left ventricular hypertrabeculation/Noncompaction in mitochondriopathy. Cardiology 10 (4) 2:228–230

    Google Scholar 

  • Finsterer J, Stöllberger C, Blazek G (2006) Neuromuscular implications in left ventricular hypertrabeculation/noncompaction. Int J Cardiol 110(3):288–300

    Article  PubMed  Google Scholar 

  • Geraghty MT, Perlman EJ, Martin LS et al (1992) Cobalamin C defect associated with hemolytic-uremic syndrome. J Pediatr 120(6):934–937

    Article  PubMed  CAS  Google Scholar 

  • Hannibal L, DiBello PM, Yu M et al (2011) The MMACHC proteome: hallmarks of functional cobalamin deficiency in humans. Mol Genet Metab 103(3):226–239

    Article  PubMed  CAS  Google Scholar 

  • Ichida F (2009) Left ventricular noncompaction. Circ J 73(1):19–26

    Article  PubMed  CAS  Google Scholar 

  • Kanemoto N, Horigome H, Nakayama J et al (2006) Interstitial 1q43-q43 deletion with left ventricular noncompaction myocardium. Eur J Med Genet 49(3):247–253

    Article  PubMed  Google Scholar 

  • 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):93–100

    Article  PubMed  CAS  Google Scholar 

  • 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):366–372

    Article  PubMed  CAS  Google Scholar 

  • 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):1295–1299

    Article  PubMed  Google Scholar 

  • 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 15

    Article  PubMed  Google Scholar 

  • Martinez HR, Belmont JW, Craigen WJ, Taylor MD, Jefferies JL (2011) Left ventricular noncompaction in Sotos syndrome. Am J Med Genet A 155A(5):1115–1118

    PubMed  Google Scholar 

  • 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):173–180

    Article  PubMed  CAS  Google Scholar 

  • McCully KS (1969) Vascular pathology of homocysteinemia:implications for the pathogenesis of arteriosclerosis. Am J Pathol 56(1):111–128

    PubMed  CAS  Google Scholar 

  • McMahon CJ, Chang AC, Pignatelli RH et al (2005) Left ventricular noncompaction cardiomyopathy in association with trisomy 13. Pediatr Cardiol 26(4):477–479

    Article  PubMed  CAS  Google Scholar 

  • 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–S83

    Article  PubMed  Google Scholar 

  • Pagliarini DJ, Calvo SR, Chang B et al (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134(1):112–123

    Article  PubMed  CAS  Google Scholar 

  • Pauli RM, Scheib-Wixted S, Cripe L et al (1999) Ventricular noncompaction and distal chromosome 5q deletion. Am J Med Genet 85(4):419–423

    Article  PubMed  CAS  Google Scholar 

  • 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):139–148

    Article  PubMed  CAS  Google Scholar 

  • 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):344–348

    Article  PubMed  CAS  Google Scholar 

  • Pupavac M, Garcia MA, Rosenblatt DS, Jerome-Majewska LA (2011) Expression of Mmachc and Mmadhc during mouse organogenesis. Mol Genet Metab 103(4):401–405

    Article  PubMed  CAS  Google Scholar 

  • 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):1158–1566

    Article  Google Scholar 

  • 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 9

    Article  PubMed  Google Scholar 

  • 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):528–538

    Article  PubMed  CAS  Google Scholar 

  • 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 1

    Article  PubMed  CAS  Google Scholar 

  • 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):1409–1413

    PubMed  Google Scholar 

  • 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):119–123

    Article  PubMed  Google Scholar 

  • 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):966–999

    Article  PubMed  Google Scholar 

  • Tang S, Batra A, Zhang Y et al (2010) Left ventricular noncompaction is associated with mutations in the mitochondrial genome. Mitochondrion 10(4):350–357

    Article  PubMed  CAS  Google Scholar 

  • 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):233–236

    Article  PubMed  Google Scholar 

  • 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):2744–2746

    Article  Google Scholar 

  • 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):71–77

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Genetics and Metabolism, Children’s National Medical Center, Washington, DC, 0010, USA

    Pranoot Tanpaiboon, Uta Lichter-Konecki & Dina Zand

  2. Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Building 49, Room 4A18, Bethesda, MD, 20892, USA

    Jennifer L. Sloan & Charles P. Venditti

  3. Child Cardiology Associates, Fairfax, VA, 22031, USA

    Patrick F. Callahan

  4. Critical Care Medicine Department, National Institutes of Health (NIH), Bethesda, MD, 20892, USA

    Dorothea McAreavey

  5. Office of the Clinical Director, Medical Genetics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA

    P. Suzanne Hart

Authors
  1. Pranoot Tanpaiboon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer L. Sloan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick F. Callahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dorothea McAreavey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Suzanne Hart
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Uta Lichter-Konecki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dina Zand
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Charles P. Venditti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles P. Venditti .

Editor information

Editors and Affiliations

  1. Sektionen für Humangenetik und Klinische, Medizinische Universität Innsbruck, Schöpfstr. 41, Innsbruck, A-6020, Austria

    Johannes Zschocke

  2. Washington State University, Clinical Pharmacology Unit, Division of Health Sciences, E. Spokane Falls Blvd. 412, Spokane, 99210-1495, Washington, USA

    K Michael Gibson

  3. , Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom

    Garry Brown

  4. Medical Center, Department of Pediatrics, Radboud University Nijmegen, Geert Grooteplein 9, Nijmegen, 6500 HB, Netherlands

    Eva Morava

  5. Heidelberg University Hospital, Center for Child and Adolescent Medicine, Im Neuenheimer Feld 430, Heidelberg, 69120, Germany

    Verena Peters

Additional information

Communicated by: Olaf Bodamer

Synopsis

Synopsis

A case report of prenatal onset left ventricular noncompaction and hydrops in cobalamin C disease.

Rights and permissions

Reprints and permissions

Copyright information

© 2012 SSIEM and Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Tanpaiboon, P. et al. (2012). Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Volume 10. JIMD Reports, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_197

Download citation

  • DOI: https://doi.org/10.1007/8904_2012_197

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-37333-6

  • Online ISBN: 978-3-642-37334-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation