Skip to main content
SpringerLink
Log in

Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature

  • Original Article
  • Published:
Pediatric Radiology Aims and scope Submit manuscript

Abstract

Background

Methylmalonic acidemia (MMA) is an autosomal-recessive inborn error of metabolism.

Objective

To recognize the CT and MR brain sectional imaging findings in children with MMA.

Materials and methods

Brain imaging studies (47 MR and 5 CT studies) from 52 children were reviewed and reported by a neuroradiologist. The clinical data were collected for each patient.

Results

The most common findings were ventricular dilation (17 studies), cortical atrophy (15), periventricular white matter abnormality (12), thinning of the corpus callosum (8), subcortical white matter abnormality (6), cerebellar atrophy (4), basal ganglionic calcification (3), and myelination delay (3). The brain images in 14 patients were normal.

Conclusion

Radiological findings of MMA are nonspecific. A constellation of common clinical and radiological findings should raise the suspicion of MMA.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Matsui SM, Mahoney MJ, Rosenberg LE (1983) The natural history of the inherited methylmalonic acidemias. N Engl J Med 308:857–861

    PubMed  CAS  Google Scholar 

  2. Coulombe JT, Shih VE, Levy HL (1981) Massachusetts metabolic disorders screening program. II. Methylmalonic aciduria. Pediatrics 67:26–31

    PubMed  CAS  Google Scholar 

  3. Mahoney MJ, Bick D (1987) Recent advances in the inherited methylmalonic acidemias. Acta Paediatr Scand 76:689–696

    Article  PubMed  CAS  Google Scholar 

  4. Saudubray JM, Ogier H, Bonnefont JP et al (1989) Clinical approach to inherited metabolic diseases in the neonatal period: a 20-year survey. J Inherit Metab Dis 12 [Suppl 1]:25–41

    Article  PubMed  Google Scholar 

  5. Scriver CR, Beaudet AL, Valle S (eds) (2001) The metabolic and molecular basis of inherited diseases. McGraw-Hill, New York

  6. Naidu S, Moser HW (1991) Value of neuroimaging in metabolic diseases affecting the CNS. AJNR 12:413–416

    PubMed  CAS  Google Scholar 

  7. Yue NC, Arnold AM, Longstreth WT et al (1997) Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the cardiovascular health study. Radiology 202:33–39

    PubMed  CAS  Google Scholar 

  8. Kanaumi T, Takashima S, Hirose S et al (2006) Neuropathology of methylmalonic acidemia in a child. Pediatr Neurol 34:156–159

    Article  PubMed  Google Scholar 

  9. Brismar J, Ozand PT (1994) CT and MR of the brain in disorders of the propionate and methylmalonate metabolism. AJNR 15:1459–1473

    PubMed  CAS  Google Scholar 

  10. Biancheri R, Cerone R, Schiaffino MC et al (2001) Cobalamin (Cbl) C/D deficiency: clinical, neurophysiological and neuroradiologic findings in 14 cases. Neuropediatrics 32:14–22

    Article  PubMed  CAS  Google Scholar 

  11. Lachman RS (2007) Taybi and Lachman’s radiology of syndromes, metabolic disorders, and skeletal dysplagias. 5th edn. Mosby-Elsevier, Philadelphia, p 507

    Google Scholar 

  12. Enns GM, Barkovich AJ, Rosenblatt DS et al (1999) Progressive neurological deterioration and MRI changes in cblC methylmalonic acidaemia treated with hydroxocobalamin. J Inherit Metab Dis 22:599–607

    Article  PubMed  CAS  Google Scholar 

  13. Barkovich AJ (2000) Pediatric neuroimaging. Williams and Wilkins, Baltimore, pp 138–139

    Google Scholar 

  14. Rutherford M (2002) MRI of the neonatal brain. Saunders, Philadelphia, PA

    Google Scholar 

  15. Jin H, Zou LP, Zhang CH et al (2004) Diagnosis and treatment of methylmalonic acidemia in 14 cases. Zhonghua Er Ke Za Zhi 42:581–584

    PubMed  Google Scholar 

  16. Gebarski SS, Gabrielsen TO, Knake JE et al (1983) Cerebral CT findings in methylmalonic acid propionic acidemias. AJNR 4:955–957

    PubMed  CAS  Google Scholar 

  17. Heidenreich R, Natowicz M, Hainline BE et al (1988) Acute extrapyramidal syndrome in methylmalonic acidemia: “metabolic stroke” involving the globus pallidus. J Pediatr 113:1022–1027

    Article  PubMed  CAS  Google Scholar 

  18. de Sousa C, Piesowicz AT, Brett EM et al (1989) Focal changes in the globi pallidi associated with neurological dysfunction in methylmalonic acidaemia. Neuropediatrics 20:199–201

    Article  PubMed  Google Scholar 

  19. Korf B, Wallman JK, Levy HL (1986) Bilateral lucency of the globus pallidus complicating methylmalonic acidemia. Ann Neurol 20:364–366

    Article  PubMed  CAS  Google Scholar 

  20. Yesildag A, Ayata A, Baykal B et al (2005) Magnetic resonance imaging and diffusion-weighted imaging in methylmalonic acidemia. Acta Radiol 46:101–103

    Article  PubMed  CAS  Google Scholar 

  21. Trinh BC, Melhem ER, Barker PB (2001) Multi-slice proton MR spectroscopy and diffusion-weighted imaging in methylmalonic acidemia: report of two cases and review of the literature. AJNR 22:831–833

    PubMed  CAS  Google Scholar 

  22. Rosenberg NL (1987) Methylmalonic acid, methanol, metabolic acidosis and lesions of the basal ganglia. Ann Neurol 22:96–97

    Article  PubMed  CAS  Google Scholar 

  23. Shimoizumi H, Okabe I, Kodama H et al (1993) Methylmalonic acidemia with bilateral MRI high intensities of the globus pallidus. No To Hattatsu 25:554–557

    PubMed  CAS  Google Scholar 

  24. Roodhooft AM, Baumgartner ER, Martin JJ et al (1990) Symmetrical necrosis of the basal ganglia in methylmalonic acidaemia. Eur J Pediatr 149:582–584

    Article  PubMed  CAS  Google Scholar 

  25. Barkovich AJ (1995) Pediatric neuroradiology. Raven Press, New York, pp 463–465

    Google Scholar 

  26. Rossi A, Cerone R, Biancheri R et al (2001) Early-onset combined methylmalonic aciduria and homocystinuria: neuroradiologic findings. AJNR 22:554–563

    PubMed  CAS  Google Scholar 

  27. Dave P, Curless RG, Steinman L (1984) Cerebellar hemorrhage complicating methylmalonic and propionic acidemia. Arch Neurol 41:1293–1296

    PubMed  CAS  Google Scholar 

  28. Fischer AQ, Challa VR, Burton BK et al (1981) Cerebellar hemorrhage complicating isovaleric academia: a case report. Neurology 31:746–748

    PubMed  CAS  Google Scholar 

  29. Barkovich AJ, Ali F, Rowley HA et al (1998) Imaging patterns of neonatal hypoglycemia. AJNR 19:523–528

    PubMed  CAS  Google Scholar 

  30. Lyon G, Kolodny EH, Pastores GM (2006) Neurology of hereditary metabolic diseases of children. McGraw-Hill, New York

    Google Scholar 

  31. Takeuchi M, Harada M, Matsuzaki K et al (2003) Magnetic resonance imaging and spectroscopy in a patient with treated methylmalonic acidemia. J Comput Assist Tomogr 27:547–551

    Article  PubMed  Google Scholar 

  32. Michel SJ, Given CA 2nd, Robertson WC Jr (2004) Imaging of the brain, including diffusion-weighted imaging in methylmalonic acidemia. Pediatr Radiol 34:580–582

    Article  PubMed  Google Scholar 

  33. Andruela CF, De Blasi R, Carella A (1991) CT and MR studies of methylmalonic acidemia. AJNR 12:410–412

    Google Scholar 

  34. Gropman AL (2005) Expanding the diagnostic and research toolbox for inborn errors of metabolism: the role of magnetic resonance spectroscopy. Mol Genet Metab 86:2–9

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St., ASB-I, L1-050, Boston, MA, 02115, USA

    Alireza Radmanesh

  2. Department of Pediatric Metabolic Disorders, Tehran University of Medical Sciences, Tehran, Iran

    Talieh Zaman

  3. Department of Radiology, Tehran University of Medical Sciences, Tehran, Iran

    Hossein Ghanaati

  4. Department of Radiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sanaz Molaei

  5. Department of Radiology, Children’s Hospital Boston, Boston, MA, USA

    Richard L. Robertson

  6. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Amir A. Zamani

Authors
  1. Alireza Radmanesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Talieh Zaman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hossein Ghanaati
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sanaz Molaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard L. Robertson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amir A. Zamani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alireza Radmanesh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Radmanesh, A., Zaman, T., Ghanaati, H. et al. Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature. Pediatr Radiol 38, 1054–1061 (2008). https://doi.org/10.1007/s00247-008-0940-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00247-008-0940-8

Keywords

Search

Navigation