Rare Infectious Disease News

Disease Profile

Malonyl-CoA decarboxylase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

E72.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Malonic aciduria; Malonicaciduria; Malonic acidemia;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Newborn Screening

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 943

Definition
Malonic aciduria is a metabolic disorder caused by deficiency of malonyl-CoA decarboxylase (MCD).

Epidemiology
It is a very rare disorder that has been described in less than 20 patients.

Clinical description
This condition usually presents in early childhood and the manifestations are variable. The majority of patients are developmentally delayed with other features that include hypotonia, seizures, hypoglycaemia, metabolic acidosis, cardiomyopathy and diarrhoea.

Etiology
The disease is caused by mutations in the malonyl-CoA decarboxylase gene (MLYCD, chromosome 16q24) and is inherited as an autosomal recessive trait. The MCD enzyme is involved in the degradation of malonyl-CoA and it appears that inhibition of fatty acid synthesis as a result of malonyl-CoA accumulation is responsible for at least some of the clinical manifestations of the disorder.

Diagnostic methods
The diagnosis of malonic aciduria can be made by detecting elevated levels of organic acids (in particular malonic and methylmalonic acid) in the urine and high levels of malonylcarnitine in the blood. The diagnosis is confirmed by demonstrating reduced enzyme activity in cultured skin fibroblasts. Identification of the MLYCD gene mutation may also be useful for diagnosis and for genetic counselling.

Antenatal diagnosis
Screening of newborns may be possible through detection of elevated blood levels of malonylcarnitine using electrospray ionisation tandem mass spectrometry (ESI-MS/MS). Prenatal screening is theoretically possible through enzyme or DNA analysis of amniocytes or chorionic villus samples.

Management and treatment
The principle treatment is dietary, with patients being recommended to follow a low fat/high carbohydrate diet. Carnitine supplements may also be recommended.

Prognosis
The prognosis for patients is variable but the disease can be lethal in the neonatal period.

Visit the Orphanet disease page for more resources.

Symptoms

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.

Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Pachygyria
Fewer and broader ridges in brain
0001302
1%-4% of people have these symptoms
Delayed CNS myelination
0002188
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Left ventricular noncompaction cardiomyopathy
0011664
Neonatal respiratory distress
Infantile respiratory distress
Newborn respiratory distress
Respiratory distress, neonatal

[ more ]

0002643
Seizure
0001250
Percent of people who have these symptoms is not available through HPO
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Autosomal recessive inheritance
0000007
Chronic constipation
Infrequent bowel movements
0012450
Constipation
0002019
Diarrhea
Watery stool
0002014
Elevated urine suberic acid level
0033213
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
Hypoglycemia
Low blood sugar
0001943
Ketosis
High levels of ketone bodies
0001946
Lactic acidosis
Increased lactate in body
0003128
Metabolic acidosis
0001942
Methylmalonic aciduria
0012120
Short stature
Decreased body height
Small stature

[ more ]

0004322
Vomiting
Throwing up
0002013

Diagnosis

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.

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.

    Organizations

    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

      Learn more

      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 Malonyl-CoA decarboxylase deficiency. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • 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.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • 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 Malonyl-CoA decarboxylase deficiency. Click on the link to view a sample search on this topic.