National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Methylmalonic acidemia with homocystinuria


Other Names:
Methylmalonic acidemia and homocystinemia
Categories:
Subtypes:
Methylmalonic acidemia and homocysteinemia type cblX; Methylmalonic acidemia with homocystinuria type cblC; Methylmalonic acidemia with homocystinuria type cblD; Methylmalonic acidemia and homocysteinemia type cblX; Methylmalonic acidemia with homocystinuria type cblC; Methylmalonic acidemia with homocystinuria type cblD; Methylmalonic acidemia with homocystinuria type cblF; Methylmalonic acidemia with homocystinuria type cblJ See More
This disease is grouped under:
Methylmalonic acidemia with homocystinuria is an inherited disorder in which the body is unable to properly process certain nutrients from food including amino acids, lipids and cholesterol. People with this disorder have a combination of features from two separate conditions: methylmalonic acidemia and homocystinuria. When the condition begins early in life, babies have difficulty gaining weight (failure to thrive), feeding difficulties, and a pale appearance. Babies may also have weak muscle tone (hypotonia) and seizures. Most babies and children with this condition have an unusually small head size (microcephaly), intellectual disability and developmental delay. Less common features of the condition include eye problems and a blood disorder called megaloblastic anemia.[1] When the disorder begins in adolescence or adulthood, the signs and symptoms usually include behavior and personality changes and cognitive problems (issues with learning, memory, perception etc). In some cases, abilities are lost, resulting in a decline of performance, memory and speech problems, dementia and lethargy.[12470[2]

Methylmalonic acidemia with homocystinuria can be caused by mutations in one of several genes: MMACHC, MMADHC, LMBRD1, ABCD4, or HCFC1. Mutations in these genes account for the different types of the disorder, cblC, cblD, cblF, cblJ, and cblX, respectively.[1] Although there is no cure for this conditions, treatment may include intramuscular injections of hydroxycobalamin, oral betaine, and folic acid.[2][3] 
Last updated: 10/31/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Amblyopia
Lazy eye
Wandering eye
[ more ] 		0000646
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Fatigue
Tired
Tiredness
[ more ] 		0012378
Feeding difficulties
Feeding problems
Poor feeding
[ more ] 		0011968
Global developmental delay 0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Lethargy 0001254
Megaloblastic bone marrow 0001980
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Muscular hypotonia
Low or weak muscle tone
0001252
Retinopathy
Noninflammatory retina disease
0000488
Seizure 0001250
30%-79% of people have these symptoms
Abnormality of cardiovascular system morphology 0030680
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
5%-29% of people have these symptoms
Skin rash 0000988
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
  • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include acquired vitamin B12 deficiency, vitamin B12-responsive methylmalonic aciduria, and homocystinuria without methylmalonic aciduria (see these terms). The combination of methylmalonic aciduria, homocystinuria and normal serum cobalamin concentrations is required to distinguish patients.
Visit the Orphanet disease page for more information.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Methylmalonic acidemia with homocystinuria. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
  • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Methylmalonic acidemia with homocystinuria. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Methylmalonic acidemia with homocystinuria. Genetics Home Reference. 2015; https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia-with-homocystinuria.
  2. Sloan JL, Carrillo N, Adams D & Venditti CP. Disorders of Intracellular Cobalamin Metabolism. GeneReviews. Updated September 6, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1328/.
  3. Methylmalonic acidemia with homocystinuria. Orphanet. 2013; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=26.