Methylmalonic Acidemia Brief Overview of Methylmalonic Acidemia
Methylmalonic acidemia is an autosomal recessive disorder of amino acid metabolism, involving a defect in the conversion of methylmalonyl-coenzyme A (CoA) to succinyl-CoA. Patients typically present at the age of 1 month to 1 year with neurologic manifestations, such as seizure, encephalopathy, and stroke. [1, 2, 3] Several cases have involved stroke in the bilateral globus pallidi as a result of methylmalonic acidemia.
Several mutations have been identified in the MUT gene resulting in MMA. There can be deletions, insertions, missense or nonmutations, and so on that lead to clinical phenotype. Mutations of the MUT gene are estimated to cause 60% of MMA cases. These mutations result in defects in the methylmalonyl-CoA mutase enzyme. The gene has been mapped to chromosome 6p12-21.2
There is reportedly 1 case of methylmalonic acidemia in 25,000-48,000 population. Nyhan and Sakati stated that the true prevalence may be higher because many neonatal deaths may be caused by unrecognized metabolic disorders. 
Go to Neuro-vascular Diseases for more information on metabolic diseases and stroke.
The main pathway of methylmalonyl-CoA production involves the metabolism of isoleucine, valine, threonine, and methionine. To a lesser extent, odd-chain fatty acid and cholesterol degradation also contribute.
Conversion of methylmalonyl-CoA to succinyl-CoA requires the enzyme methylmalonyl-CoA mutase and the cofactor 5′-deoxyadenosylcobalamin. Methylmalonic acidemia can manifest itself differently depending on the following factors  :
Absence of enzyme (mut0)
Reduction in enzyme activity (mut-)
Defect in the synthesis of 5′-deoxyadenosylcobalamin (cblA, cblB, cblH)
Reduced blood flow or faulty oxidative metabolism may cause strokes in methylmalonic acidemia. The sequence of events in reduced blood flow may be acidosis, hypocapnia, and vasoconstriction. Several magnetic resonance spectroscopic studies have shown that lactate accumulates in areas of the brain that are damaged in methylmalonic acidemia.
Some authors suggest that the accumulation of methylmalonic acid and odd-chain fatty acids may be directly toxic to neuronal and glial cells. This toxic effect may impair oxidative metabolism, leading to infarctions. An alternate hypothesis suggests that toxic metabolites may result from treatment with cyanocobalamin, which metabolizes to cyanide, a known central nervous system toxin.
Based on reports of liver transplantation reports meant to address the issue of metabolic derangement in methylmalonic acidemia, the neurologic consequences of methylmalonic acidemia may not be a result of metabolic abnormalities in the liver; rather, they may be a local metabolic disturbance in the brain. Liver transplantation did not prevent further neurologic worsening or occurrence of strokelike episodes. [7, 8, 9, 10, 11]
A knock-out mouse model similar to the mut0 human form of methylmalonic acidemia has been developed.  This model may facilitate further research into the pathophysiology of the disease and broaden its therapeutic options.
In a study of 21 Indian patients, 70 mutations were identified. Although there are 13 exons of the MUT gene, the most deleterious mutations were located in exon 12, then exon 9, exon 11, and exon 2. Though there is a wide spectrum of mutations found in MMA, this study, consistent with previous studies, showed that missense mutations were the highest contributors to the phenotype. 
Children with methylmalonic acidemia may be healthy at birth and develop symptoms soon after starting protein intake. The patient’s family history may be positive for methylmalonic acidemia (eg, siblings with similar episodes of recurrent illnesses or with acidopathy).
In most children, the disease is diagnosed in the middle of an episode of metabolic decompensation.  Vomiting, dehydration, lethargy, seizures, recurrent infections, and progressive encephalopathy are some features of methylmalonic acidemia. These metabolic perturbations can be caused by an infection or a change in feeding habit. Some children may present with strokes during a metabolic crisis.
Methylmalonic acidemia due to derangement of adenosylcobalamin synthesis (cblA, cblB, cblH) and cobalamin catabolism (cblC, cblD, cblF) may have features not shared by pure methylmalonyl-CoA mutase disorders.
A case study of a 4-year-old girl with MMA with partial clbC subtype showed that onset of disease can be following aHUS as opposed to neurological damage which is more common. 
There have been cases of late-onset cblC form of disease reported. Most presented with neurological symptoms including cognitive decline, hypertensive encephalopathy, unsteady gait, myelopathy, and behavioral abnormalities. One study reports two siblings with late-onset cblC which presented with manic-depressive psychosis at the first onset. As this late-onset form of MMA is rare, inclusion of psychiatric symptoms as a first symptom may help yield higher diagnostic results. 
Hypotonia, lethargy, failure to thrive, hepatosplenomegaly, and monilial infections are some classic findings. In patients with methylmalonic acidemia, acute onset of choreoathetosis, dystonia, dysphagia, or dysarthria should alert the physician to the possibility of stroke. Neurologic manifestations may be present, even in the absence of more traditional findings.
The majority of MMA onset from neurological damage, but some cases may first onset with unusal presentations such as mimicked diabetic ketoacidosis, late-onset diffuse lung disease, and juvenile gout. 
Signs, symptoms, and nonspecific presentation generally make the diagnosis of methylmalonic 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
The 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
Patent foramen ovale
Sickle cell disease
Go to Inherited Metabolic Disorders, First Seizure: Pediatric Perspective, Complex Partial Seizures, Moyamoya Disease, Neurofibromatosis, Type 1, Posterior Cerebral Artery Stroke, Staphylococcal Meningitis, and Tuberous Sclerosis for more information on these topics
The following conditions should also be considered in the evaluation of cases of suspected methylmalonic acidemia:
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.
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.
When acidosis is suspected on the basis of electrolyte and arterial blood gas (ABG) 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.
Blood levels 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.
Complete blood cell (CBC) counts may reveal neutropenia, anemia, and thrombocytopenia, the result of the downregulation of hematopoietic growth, which may also be present during acute episodes of infection or metabolic decompensation.
Gas chromatography-mass spectrometry can be used for the organic acid in urine, blood, and cerebrospinal fluid.
Mutation analysis is the most reliable evidence for MMA and can be accomplished by Next-Generation sequencing as well as Sanger sequencing.
The American College of Medical Genetics and National Academy of Clinical Biochemistry recommends early diagnosis by means of newborn screening. While newborn screening for metabolic disorders is not currently used in all countries, there have been improvements in reliable determination of MMA in dried blood spots. Using liquid chromatography-tandem mass spectrometry, this assay can effectively and reliably differentiate patients with propionic acidemia, methymalonic acidemias, and combined remethylation disorders. 
Neuroimaging study is always warranted when patients have a change in neurologic status (eg, seizures, lethargy, progressive encephalopathy, choreoathetosis, dystonia, dysarthria).
Magnetic resonance imaging (MRI) and computed tomography (CT) studies have commonly shown bilateral lesions of the globus pallidus in patients with methylmalonic acidemia. [22, 23, 24, 25, 26, 27, 28, 29, 30] 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, and intracranial hemorrhage can occur if the metabolic derangement includes a bleeding diathesis.
In an acute phase, identify and treat intercurrent infections that triggered the acidotic episode. Correct the acidosis; dialysis may be required in cases of severe ketoacidosis and hyperammonemia. A case report noted a decrease in ammonia levels with the use of carbamylglutamate in preference to dialysis alone. 
Dietary modifications must be made in a hospital setting. Outcomes are better in patients with cobalamin-responsive disease than in those with the cobalamin-nonresponsive disease, in association with dietary changes and supplementation of carnitine and cobalamin. [32, 33]
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.
Levo-carnitine (L-carnitine) is a dietary supplement that 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.
Patients with MMA are prone to anorexia and often need a temporary or permanent method for enteral feeding. When appropriate, tube feeding should be used. 
Treatment strategies for MMA are designed to reduce metabolic poisons and/or to accelerate their clearance. 
Implement a protein-restricted diet (0.5-1.5 g/kg/d) with L-carnitine and cobalamin supplementation.
Cobalamin supplementation may help because cobalamin is a cofactor in the enzymatic conversion of methylmalonyl-coenzyme A (CoA) to succinyl-CoA. This therapy can be started while the diagnosis is being confirmed. If cobalamin supplementation is not helpful, restrict the patient’s isoleucine, threonine, methionine, and valine intake. The typical formulation and starting dosage is hydroxocobalamin 1000 μg intramuscular once daily.
L-carnitine, an enzyme involved in the metabolism of long-chain fatty acids, buffers the acyl-CoA metabolites that accumulate with protein-restricted diets. Acyl-carnitine produced by this buffering action is excreted in the urine.
Response to cobalamin supplementation and dietary changes may be monitored in terms of clinical and laboratory improvement. Quantitative measurement of methylmalonic acid in the urine can monitor the success of therapy.
Medical dietary changes are often critical for therapy in inborn errors of metabolism, however, their optimal composition is under review by researchers. The combination of protein restriction and high leucine content in medical foods may have unintended effects such as imbalanced branched-chain amino acid (BCAA) content, which could lead to decreased plasma levels of valine and isoleucine and predicts impairment of brain uptake of essential amino acids. 
Candidal infection may be the first sign that treatment adjustments are necessary.
Liver transplantation alone or in conjunction with kidney transplantation has been attempted. Organ transplantation may not prevent future neurologic damage or reverse old damage. [7, 8, 9, 10, 11, 36, 37, 38] Since the liver is the site of most of the metabolic conversion of propionate, replacing the liver may contribute enough enzyme activity to avert metabolic decompensation. Although liver transplant may help to protect against metabolic instability, it is not a cure and MMA patients still remain at risk for long-term complications. 
Low sodium bicarbonate levels should be treated aggressively. This formula can be used to calculate the mmol of base to provide for half-correction, which is an appropriate goal for the first 24 hours of treatment. [Desired bicarbonate level (mmol/L) – current bicarbonate level (mmol/L)] × [volume of distribution (0.7 in neonate; 0.6 in older child and adult) × body weight (kg)] × [0.5]. 
Hemodialysis is indicated when initial ammonia levels are greater than 500μmol/L. Nephrology should be consulted in this case. 
Regular medical screenings for known complications of MMA are recommended for optimal management of disease.
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.
Consult a neurologist when seizures, choreoathetosis, dysarthria, or stroke occur. Consider offering genetic counseling to the patient’s family, especially if more than 1 child has aminoacidopathy.
Consultation with a registered dietitian is also in order, because protein restriction is an essential part of treatment, and consider consultation with a physical and occupational therapist, as they may help in functionally retraining patients.
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.
In a study of 35 families affected by MMA, health-related quality of life was evaluated using the Pediatric Quality of Life Inventory (PedsQL™) parent version.  Children with MMA mut0 had a lower mean score on the Generic Core Scales than healthy children with the most impaired domains in social and school functioning. This indicates that children living with MMA have substantial impairments in quality of life, and their families also showed significant impairments in cognitive functioning, worry, family relationships, and daily activities. 
Counseling should be provided to families with newly diagnosed children in anticipation of the impaired domains in quality of life. Children with MMA may require additional educational and social support and early interventions may help improve outcomes.
Over the last 3 decades, observations of patients have revealed that their response to treatment is correlated with their prognosis. Of the 9 recognized defects in methylmalonate metabolism, cblA has the best prognosis; mut0, the worst. The remaining classes (cblB, cblC, cblD, cblE, cblF, clbG) have intermediate prognoses. cblH is a newly identified variant of cblA.
Patients with cobalamin-responsive disease may reach some early developmental milestones, and they may have long-term prognoses better than those of the other group. However, this group remains at risk for acute decompensation, which may result in clinical signs and symptoms of globus pallidal lesions.
While transplantation may help improve metabolic stability, the CNS remains at high ongoing risk regardless.  Early transplantation may help to maintain neurological development and improve growth of patients and in one study of 13 Japanese MMA patients, 10 were free of acidosis attacks following transplantation. 
In a cross-sectional study of 35 patients from the United Kingdom, early-onset cobalamin-nonresponders had the worst outcomes, with a median survival of approximately 6 years.  Neurologic outcomes remained unchanged despite dietary modifications and management of infections.
In a case study of 4 children with combined methylmalonic acidemia and homocysteinemia, all developed diffuse lung diseases. This study indicates that the combination of MMA and homocysteinemia may be the primary cause of diffuse lung diseases in this cohort of patients. It also presents justification for combined MMA and homocysteinemia to be considered in the differential diagnosis of diffuse lung diseases.
As more cases are evaluated, better therapies for these patients will emerge. Clinicians treating cases of MMA should stay up-to-date on progressive therapies and trials to provide optimal care to their patients.
Fenton WA, Rosenberg LE. Disorders of propionate and methylmalonate metabolism. Scriver CR, ed. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill; 1995. Vol 1: 1423-49.
Fenichel GM. Clinical Pediatric Neurology: A Signs and Systems Approach. 1996:12.
Swaiman KF. Aminoacidopathies and organic acidemias resulting from deficiency of enzyme activity. Pediatric Neurology. Principles and Practice. 1995. 1215-19.
Nyhan WL, Sakati NA. Methyl malonic acidemia. Diagnostic Recognition of Genetic Disease. 1987. 42-50.
Matsui SM, Mahoney MJ, Rosenberg LE. The natural history of the inherited methylmalonic acidemias. N Engl J Med. 1983 Apr 14. 308(15):857-61. [Medline].
Carrillo-Carrasco N, Chandler RJ, Venditti CP. Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management. J Inherit Metab Dis. 2012 Jan. 35(1):91-102. [Medline].
Chakrapani A, Sivakumar P, McKiernan PJ, Leonard JV. Metabolic stroke in methylmalonic acidemia five years after liver transplantation. J Pediatr. 2002 Feb. 140(2):261-3. [Medline].
Nyhan WL, Gargus JJ, Boyle K, et al. Progressive neurologic disability in methylmalonic acidemia despite transplantation of the liver. Eur J Pediatr. 2002 Jul. 161(7):377-9. [Medline].
Deodato F, Boenzi S, Santorelli FM, Dionisi-Vici C. Methylmalonic and propionic aciduria. Am J Med Genet C Semin Med Genet. 2006 May 15. 142(2):104-12. [Medline].
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. 2006 Aug. 88(4):322-6. [Medline].
Kasahara M, Horikawa R, Tagawa M, et al. Current role of liver transplantation for methylmalonic acidemia: a review of the literature. Pediatr Transplant. 2006 Dec. 10(8):943-7. [Medline].
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. 2002 Nov 26. 99(24):15554-9. [Medline].
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. 2000 Jul. 37(7):510-3. [Medline].
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. 2002 Dec 15. 11(26):3361-9. [Medline].
Sawangareetrakul P, Ketudat Cairns JR, Vatanavicharn N, Liammongkolkul S, et al. Analysis of Novel Mutations and Methylmalonyl-CoA Mutase Levels in Thai Patients with Isolated Methylmalonic Acidemia. Biochem Genet. 2015 Sep 14. [Medline].
Peters H, Nefedov M, Sarsero J, et al. A knock-out mouse model for methylmalonic aciduria resulting in neonatal lethality. J Biol Chem. 2003 Dec 26. 278(52):52909-13. [Medline].
Kumari C, Kapoor S, Varughese B, Pollipali SK, Ramji S. Mutation Analyses in Selected Exons of the MUT Gene in Indian Patients with Methylmalonic Acidemia. Indian J Clin Biochem. 2017 Jul. 32 (3):266-274. [Medline].
Parini R, Furlan F, Brambilla A, Codazzi D, Vedovati S, Corbetta C, et al. Severe Neonatal Metabolic Decompensation in Methylmalonic Acidemia Caused by CblD Defect. JIMD Rep. 2013. 11:133-7. [Medline]. [Full Text].
Chen M, Zhuang J, Yang J, Wang D, Yang Q. Atypical hemolytic uremic syndrome induced by CblC subtype of methylmalonic academia: A case report and literature review. Medicine (Baltimore). 2017 Oct. 96 (43):e8284. [Medline].
Wu LY, An H, Liu J, Li JY, Han Y, Zhou AH, et al. Manic-depressive Psychosis as the Initial Symptom in Adult Siblings with Late-onset Combined Methylmalonic Aciduria and Homocystinemia, Cobalamin C Type. Chin Med J (Engl). 2017 Feb 20. 130 (4):492-494. [Medline].
Monostori, P., Klinke, G., Richter, S., et al. Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders. PLoS One.
Heidenreich R, Natowicz M, Hainline BE, et al. Acute extrapyramidal syndrome in methylmalonic acidemia: “metabolic stroke” involving the globus pallidus. J Pediatr. 1988 Dec. 113(6):1022-7. [Medline].
Korf B, Wallman JK, Levy HL. Bilateral lucency of the globus pallidus complicating methylmalonic acidemia. Ann Neurol. 1986 Sep. 20(3):364-6. [Medline].
Larnaout A, Mongalgi MA, Kaabachi N, et al. Methylmalonic acidaemia with bilateral globus pallidus involvement: a neuropathological study. J Inherit Metab Dis. 1998 Aug. 21(6):639-44. [Medline].
Brismar J, Ozand PT. CT and MR of the brain in disorders of the propionate and methylmalonate metabolism. AJNR Am J Neuroradiol. 1994 Sep. (8):1459-73. [Medline].
Brismar J, Ozand PT. CT and MR of the brain in the diagnosis of organic acidemias. Experiences from 107 patients. Brain Dev. 1994 Nov. 16 Suppl:104-24. [Medline].
Takeuchi M, Harada M, Matsuzaki K, et al. Magnetic resonance imaging and spectroscopy in a patient with treated methylmalonic acidemia. J Comput Assist Tomogr. 2003 Jul-Aug. 27(4):547-51. [Medline].
Michel SJ, Given CA, Robertson WC. Imaging of the brain, including diffusion-weighted imaging in methylmalonic acidemia. Pediatr Radiol. 2004 Jul. 34(7):580-2. [Medline].
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. 2008 Jun. 31(3):368-78. [Medline].
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. 2008 Oct. 38(10):1054-61. [Medline].
Gebhardt B, Vlaho S, Fischer D, et al. N-carbamylglutamate enhances ammonia detoxification in a patient with decompensated methylmalonic aciduria. Mol Genet Metab. 2003 Aug. 79(4):303-4. [Medline].
Manoli I, Myles JG, Sloan JL, Carrillo-Carrasco N, Morava E, et al. A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 2: cobalamin C deficiency. Genet Med. 2015 Aug 13. [Medline].
Manoli I, Myles JG, Sloan JL, Shchelochkov OA, Venditti CP. A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: isolated methylmalonic acidemias. Genet Med. 2015 Aug 13. [Medline].
Aldubayan SH, Rodan LH, Berry GT, Levy HL. Acute Illness Protocol for Organic Acidemias: Methylmalonic Acidemia and Propionic Acidemia. Pediatr Emerg Care. 2017 Feb. 33 (2):142-146. [Medline].
Myles JG, Manoli I, Venditti CP. Effects of medical food leucine content in the management of methylmalonic and propionic acidemias. Curr Opin Clin Nutr Metab Care. 2018 Jan. 21 (1):42-48. [Medline].
Leonard JV, Walter JH, McKiernan PJ. The management of organic acidaemias: the role of transplantation. J Inherit Metab Dis. 2001 Apr. 24(2):309-11. [Medline].
Brassier A, Boyer O, Valayannopoulos V, Ottolenghi C, Krug P, Cosson MA, et al. Renal transplantation in 4 patients with methylmalonic aciduria: a cell therapy for metabolic disease. Mol Genet Metab. 2013 Sep-Oct. 110(1-2):106-10. [Medline].
Niemi AK, Kim IK, Krueger CE, Cowan TM, Baugh N, et al. Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation. J Pediatr. 2015 Jun. 166 (6):1455-61.e1. [Medline].
Splinter K, Niemi AK, Cox R, Platt J, Shah M, Enns GM, et al. Impaired Health-Related Quality of Life in Children and Families Affected by Methylmalonic Acidemia. J Genet Couns. 2016 Oct. 25 (5):936-44. [Medline].
Fraser JL, Venditti CP. Methylmalonic and propionic acidemias: clinical management update. Curr Opin Pediatr. 2016 Dec. 28 (6):682-693. [Medline].
Sakamoto R, Nakamura K, Kido J, Matsumoto S, Mitsubuchi H, Inomata Y, et al. Improvement in the prognosis and development of patients with methylmalonic acidemia after living donor liver transplant. Pediatr Transplant. 2016 Dec. 20 (8):1081-1086. [Medline].
Nicolaides P, Leonard J, Surtees R. Neurological outcome of methylmalonic acidaemia. Arch Dis Child. 1998 Jun. 78(6):508-12. [Medline].
Moras E, Hosack A, Watkins D, Rosenblatt DS. Mitochondrial vitamin B12-binding proteins in patients with inborn errors of cobalamin metabolism. Mol Genet Metab. 2007 Feb. 90 (2):140-7. [Medline].
Ledley FD, Lumetta MR, Zoghbi HY, VanTuinen P, Ledbetter SA, Ledbetter DH. Mapping of human methylmalonyl CoA mutase (MUT) locus on chromosome 6. Am J Hum Genet. 1988 Jun. 42 (6):839-46. [Medline].
Liu J, Peng Y, Zhou N, Liu X, Meng Q, Xu H, et al. Combined methylmalonic acidemia and homocysteinemia presenting predominantly with late-onset diffuse lung disease: a case series of four patients. Orphanet J Rare Dis. 2017 Mar 21. 12 (1):58. [Medline].
Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP Chief, Pediatric Neurology, Tulane Medical Center and Tulane-Lakeside Hospital; Pediatric Neurology Telemedicine/EEG, Women’s and Children’s Hospital and Lakeview Regional Medical Center; Associate Professor of Pediatrics, Neurology, Neurosurgery, and Psychiatry, Medical Director, Tulane Center for Autism and Related Disorders, Co-Director, Developmental Neurogenetics Center, Tulane University School of Medicine; Assistant Professor of Pediatrics, Neurology, and Psychiatry, Uniformed Services University of the Health Sciences
Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Medical Association, Association of Military Surgeons of the US, Child Neurology Society, Southern Pediatric Neurology Society
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Biomarin; Supernus<br/>Received income in an amount equal to or greater than $250 from: Biomarin; Supernus; American Board of Pediatrics.
Brittany Y Gerstein, MSc Clinical Research Specialist, Memorial Sloan Kettering Cancer Center; Masters of Neuroscience, Tulane University
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
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 Neurological Association, American Society of Neurorehabilitation, American Academy of Neurology, American Heart Association, American Medical Association, National Stroke Association, Phi Beta Kappa, Tennessee Medical Association
Disclosure: Nothing to disclose.
Helmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center
Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Executive Committee for the NINDS-funded DEFUSE3 Trial; Physician Advisory Board for Coherex Medical.
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
Disclosure: Nothing to disclose.
Richard M Zweifler, MD Chief of Neurosciences, Sentara Healthcare; Professor and Chair of Neurology, Eastern Virginia Medical School
Richard M Zweifler, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association, Stroke Council of the American Heart Association, American Heart Association, American Medical Association
Disclosure: Nothing to disclose.
Thomas A Kent, MD Professor and Director of Stroke Research and Education, Department of Neurology, Baylor College of Medicine; Chief of Neurology, Michael E DeBakey Veterans Affairs Medical Center
Thomas A Kent, MD is a member of the following medical societies: American Academy of Neurology, Royal Society of Medicine, Stroke Council of the American Heart Association, American Neurological Association, New York Academy of Sciences, Sigma Xi
Disclosure: Nothing to disclose.
Methylmalonic Acidemia Brief Overview of Methylmalonic Acidemia
Research & References of Methylmalonic Acidemia Brief Overview of Methylmalonic Acidemia|A&C Accounting And Tax Services