eMedicine Specialties > Neurology > Neuro-vascular Diseases

Metabolic Disease and Stroke - Methylmalonic Acidemia: Differential Diagnoses & Workup

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

Differential Diagnoses

Anterior Circulation Stroke
Metabolic Disease & Stroke: Hyperglycemia/Hypoglycemia
Blood Dyscrasias and Stroke
Metabolic Disease & Stroke: MELAS
Complex Partial Seizures
Metabolic Disease & Stroke: Propionic Acidemia
Fibromuscular Dysplasia
Moyamoya Disease
First Seizure: Pediatric Perspective
Neurofibromatosis, Type 1
Haemophilus Meningitis
Posterior Cerebral Artery Stroke
Hyperammonemia
Staphylococcal Meningitis
Inherited Metabolic Disorders
Tuberous Sclerosis
Intracranial Hemorrhage
Metabolic Disease & Stroke: Fabry Disease
Metabolic Disease & Stroke: Homocystinuria/Homocysteinemia

Other Problems to Be Considered

More common etiologies of stroke are broadly classified as cardiac, infectious, hematologic, vascular, genetic, or metabolic.

The following problems are associated with pediatric strokes:
Cyanotic heart disease
Diabetes mellitus
Endocarditis
Ehlers-Danlos syndrome
Marfan syndrome
Mitochondrial cytopathies
Moyamoya syndrome
Organic acidurias
Patent foramen ovale
Sickle cell disease
Thrombocytopenia

Workup

Laboratory Studies

  • When acidosis is suspected on the basis of electrolyte and arterial blood gas abnormalities, common causes of ketoacidosis and lactic acidosis must be eliminated first. Diabetes, alcoholic ketoacidosis, liver disease, shock, anoxic and/or ischemic injury of tissues, and seizures are often associated with acidosis.
  • If the clinical picture suggests a metabolic disorder, a presumptive diagnosis can be made on the basis of blood analysis for ammonia levels, amino acids, and organic acids. Also perform concomitant urinalysis for amino acids and organic acids.
    • Blood level of ammonia, glycine, and methylmalonic acid are elevated.
    • Serum levels of propionic acid, which is upstream in the metabolic pathway of amino acids, may also be elevated.
    • Urine levels of methylmalonic acid, methylcitrate, propionic acid, and 3-hydroxypropionate levels are high.
    • Definitive diagnosis is made after enzyme analysis of fibroblasts in search of the specific enzyme abnormality.
  • CBC counts may reveal neutropenia, anemia, and thrombocytopenia, the result of the downregulation of hematopoietic growth, which also may be present during acute episodes of infection or metabolic decompensation.
  • Perform blood, imaging, and cardiac studies as part of the workup in a patient in whom stroke is suspected. Exclude other various causes of strokes in the pediatric population.

Imaging Studies

  • Neuroimaging study is always warranted when patients have a change in neurologic status (eg, seizures, lethargy, progressive encephalopathy, choreoathetosis, dystonia, dysarthria).
  • MRI and CT studies have commonly shown bilateral lesions of the globus pallidus in patients with methylmalonic acidemia. Imaging abnormalities extending beyond the basal ganglia have also been reported. These abnormalities include delayed myelination, immature gyral pattern and periventricular white matter lesions.
  • Small hemorrhages in the brainstem and cerebellum have also been reported. 
  • Intracranial hemorrhage can occur if the metabolic derangement includes a bleeding diathesis.

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
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References

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Further Reading

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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

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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

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