eMedicine Specialties > Neurology > Neuro-vascular Diseases

Metabolic Disease and Stroke - Methylmalonic Acidemia: Follow-up

Author: Pitchaiah Mandava, MD, PhD, Assistant Professor, Department of Neurology, Baylor College of Medicine; Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center
Coauthor(s): Thomas A Kent, MD, Professor, Department of Neurology, Baylor College of Medicine; Neurology Care Line Executive, Michael E DeBakey Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Dec 11, 2008

Follow-up

Inpatient & Outpatient Medications

  • Immediately prescribe a protein-restricted diet when an acidemia is a diagnostic consideration. This modification decreases the key amino acids (eg, isoleucine, valine, threonine, methionine) that enter the metabolic pathway.
  • Try cyanocobalamin, even in patients whose disease does not respond while a definitive diagnosis is pending. The rationale is that adenosylcobalamin acts as a cofactor for methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl CoA.
  • L-carnitine, a dietary supplement, is also used to treat all patients with methylmalonic acidemia, who apparently have a relative carnitine deficiency. The D-isomer of carnitine may not be therapeutic.

Transfer

  • Acidemias are complex diseases and require multispecialty care for diagnosis and treatment.
  • Patients are best evaluated and treated in tertiary care centers.
  • In the acute phase of illness, life-threatening issues, such as acidosis and the need for dialysis, can be assessed and treated locally.
  • After stabilization, patients may be transferred if the necessary treatment and/or diagnostic modalities are not available locally.

Prognosis

Of the 6 recognized defects in methylmalonate metabolism, cblA has the best prognosis; mut0, the worst. The remaining classes (cblB, cblC, cblD, cblF) have intermediate prognoses. cblH is a newly identified variant of cblA.

Patient Education

  • Education of the patient's family, specifically the parents, plays a critical role in the care of patients.
  • Recognition of poor feeding, vomiting, dehydration, hypotonia, respiratory distress, and seizure may help in identifying ongoing metabolic decompensation.
  • For excellent patient education resources, visit eMedicine's Stroke Center. Also, see eMedicine's patient education article Stroke.

Miscellaneous

Medicolegal Pitfalls

  • Signs, symptoms, and nonspecific presentation generally make the diagnosis of acidemia difficult.
  • If the patient's family or sibling history suggests a diagnosis of acidemia, prenatal and neonatal diagnosis must be pursued aggressively. Early diagnosis and treatment may delay the progression of symptoms.
 


More on Metabolic Disease and Stroke - Methylmalonic Acidemia

Overview: Metabolic Disease and Stroke - Methylmalonic Acidemia
Differential Diagnoses & Workup: Metabolic Disease and Stroke - Methylmalonic Acidemia
Treatment & Medication: Metabolic Disease and Stroke - Methylmalonic Acidemia
Follow-up: Metabolic Disease and Stroke - Methylmalonic Acidemia
References
[ CLOSE WINDOW ]

References

  1. Nyhan WL, Sakati NA. Methyl malonic acidemia. In: Diagnostic Recognition of Genetic Disease. 1987:42-50.

  2. Brismar J, Ozand PT. CT and MR of the brain in disorders of the propionate and methylmalonate metabolism. AJNR Am J Neuroradiol. Sep 1994;(8):1459-73. [Medline].

  3. Brismar J, Ozand PT. CT and MR of the brain in the diagnosis of organic acidemias. Experiences from 107 patients. Brain Dev. Nov 1994;16 Suppl:104-24. [Medline].

  4. Chakrapani A, Sivakumar P, McKiernan PJ, Leonard JV. Metabolic stroke in methylmalonic acidemia five years after liver transplantation. J Pediatr. Feb 2002;140(2):261-3. [Medline].

  5. Deodato F, Boenzi S, Santorelli FM, Dionisi-Vici C. Methylmalonic and propionic aciduria. Am J Med Genet C Semin Med Genet. May 15 2006;142(2):104-12. [Medline].

  6. Dobson CM, Wai T, Leclerc D, et al. Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements. Proc Natl Acad Sci U S A. Nov 26 2002;99(24):15554-9. [Medline].

  7. Dobson CM, Wai T, Leclerc D, et al. Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria. Hum Mol Genet. Dec 15 2002;11(26):3361-9. [Medline].

  8. Fenichel GM. Clinical Pediatric Neurology: A Signs and Systems Approach. 1996:12.

  9. Fenton WA, Rosenberg LE. Disorders of propionate and methylmalonate metabolism. In: Scriver CR, ed. The Metabolic and Molecular Bases of Inherited Disease. Vol 1. New York: McGraw-Hill; 1995:1423-49.

  10. Gebhardt B, Vlaho S, Fischer D, et al. N-carbamylglutamate enhances ammonia detoxification in a patient with decompensated methylmalonic aciduria. Mol Genet Metab. Aug 2003;79(4):303-4. [Medline].

  11. Harting I, Seitz A, Geb S, Zwickler T, Porto L, Lindner M, et al. Looking beyond the basal ganglia: the spectrum of MRI changes in methylmalonic acidaemia. J Inherit Metab Dis. Jun 2008;31(3):368-78. [Medline].

  12. Heidenreich R, Natowicz M, Hainline BE, et al. Acute extrapyramidal syndrome in methylmalonic acidemia: "metabolic stroke" involving the globus pallidus. J Pediatr. Dec 1988;113(6):1022-7. [Medline].

  13. Hoffmann GF, Gibson KM, Trefz FK, et al. Neurological manifestations of organic acid disorders. Eur J Pediatr. 1994;153(7 Suppl 1):S94-100. [Medline].

  14. Kanaumi T, Takashima S, Hirose S, et al. Neuropathology of methylmalonic acidemia in a child. Pediatr Neurol. Feb 2006;34(2):156-9. [Medline].

  15. Kaplan P, Ficicioglu C, Mazur AT, et al. Liver transplantation is not curative for methylmalonic acidopathy caused by methylmalonyl-CoA mutase deficiency. Mol Genet Metab. Aug 2006;88(4):322-6. [Medline].

  16. Kasahara M, Horikawa R, Tagawa M, et al. Current role of liver transplantation for methylmalonic acidemia: a review of the literature. Pediatr Transplant. Dec 2006;10(8):943-7. [Medline].

  17. Korf B, Wallman JK, Levy HL. Bilateral lucency of the globus pallidus complicating methylmalonic acidemia. Ann Neurol. Sep 1986;20(3):364-6. [Medline].

  18. Larnaout A, Mongalgi MA, Kaabachi N, et al. Methylmalonic acidaemia with bilateral globus pallidus involvement: a neuropathological study. J Inherit Metab Dis. Aug 1998;21(6):639-44. [Medline].

  19. Leonard JV, Walter JH, McKiernan PJ. The management of organic acidaemias: the role of transplantation. J Inherit Metab Dis. Apr 2001;24(2):309-11. [Medline].

  20. Mass General Hosp. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 39-1998. A 13-year-old girl with a relapsing-remitting neurologic disorder [clinical conference]. N Engl J Med. Dec 24 1998;339(26):1914-23. [Medline].

  21. Matsui SM, Mahoney MJ, Rosenberg LE. The natural history of the inherited methylmalonic acidemias. N Engl J Med. Apr 14 1983;308(15):857-61. [Medline].

  22. Michel SJ, Given CA, Robertson WC. Imaging of the brain, including diffusion-weighted imaging in methylmalonic acidemia. Pediatr Radiol. Jul 2004;34(7):580-2. [Medline].

  23. Nicolaides P, Leonard J, Surtees R. Neurological outcome of methylmalonic acidaemia. Arch Dis Child. Jun 1998;78(6):508-12. [Medline].

  24. Nyhan WL, Gargus JJ, Boyle K, et al. Progressive neurologic disability in methylmalonic acidemia despite transplantation of the liver. Eur J Pediatr. Jul 2002;161(7):377-9. [Medline].

  25. Peters H, Nefedov M, Sarsero J, et al. A knock-out mouse model for methylmalonic aciduria resulting in neonatal lethality. J Biol Chem. Dec 26 2003;278(52):52909-13. [Medline].

  26. Powers JM, Rosenblatt DS, Schmidt RE, et al. Neurological and neuropathologic heterogeneity in two brothers with cobalamin C deficiency. Ann Neurol. Mar 2001;49(3):396-400. [Medline].

  27. Radmanesh A, Zaman T, Ghanaati H, Molaei S, Robertson RL, Zamani AA. Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature. Pediatr Radiol. Oct 2008;38(10):1054-61. [Medline].

  28. Roze E, Gervais D, Demeret S, et al. Neuropsychiatric disturbances in presumed late-onset cobalamin C disease. Arch Neurol. Oct 2003;60(10):1457-62. [Medline].

  29. Swaiman KF. Aminoacidopathies and organic acidemias resulting from deficiency of enzyme activity. In: Pediatric Neurology. Principles and Practice. 1995:1215-19.

  30. Takeuchi M, Harada M, Matsuzaki K, et al. Magnetic resonance imaging and spectroscopy in a patient with treated methylmalonic acidemia. J Comput Assist Tomogr. Jul-Aug 2003;27(4):547-51. [Medline].

  31. Thompson GN, Christodoulou J, Danks DM. Metabolic stroke in methylmalonic acidemia [letter]. J Pediatr. Sep 1989;115(3):499-500. [Medline].

  32. Watkins D, Matiaszuk N, Rosenblatt DS. Complementation studies in the cblA class of inborn error of cobalamin metabolism: evidence for interallelic complementation and for a new complementation class (cblH). J Med Genet. Jul 2000;37(7):510-3. [Medline].

  33. Zweifler RM. Management of acute stroke. South Med J. Apr 2003;96(4):380-5. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

methylmalonic acidemia, metabolic disease and stroke, MMA, amino acid metabolism, methylmalonyl-coenzyme A, CoA, succinyl-CoA, seizure, encephalopathy, stroke, globus pallidi bilaterally, methylmalonic acidemia, MMAA, MMAB

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Pitchaiah Mandava, MD, PhD, Assistant Professor, Department of Neurology, Baylor College of Medicine; Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center
Pitchaiah Mandava, MD, PhD is a member of the following medical societies: American Academy of Neurology, Sigma Xi, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Coauthor(s)

Thomas A Kent, MD, Professor, Department of Neurology, Baylor College of Medicine; Neurology Care Line Executive, Michael E DeBakey Veterans Affairs Medical Center
Thomas A Kent, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences, Royal Society of Medicine, Sigma Xi, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Medical Editor

Richard M Zweifler, MD, Chief of Neurology, Sentara Healthcare, Norfolk, VA
Richard M Zweifler, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Medical Association, American Stroke Association, Royal Society of Medicine, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Howard S Kirshner, MD, Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center
Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neurorehabilitation, National Stroke Association, Phi Beta Kappa, and Tennessee Medical Association
Disclosure: Boehringer Ingelheim Honoraria Speaking and teaching; BMS/Sanofi Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD, Professor, Department of Neurology, Oregon Health and Science University; Associate Director, Oregon Stroke Center
Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology and American Stroke Association
Disclosure: Co-Axia Consulting fee Review panel membership; Talecris Consulting fee Review panel membership; AGA Medical Consulting fee Review panel membership; Boehringer Ingelheim Honoraria Speaking and teaching; Concentric Medical Consulting fee Review panel membership; Abbott Consulting fee Consulting; Sanofi  Consulting

RELATED EMEDICINE ARTICLES
Patient Education
 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.