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Deficiency of malonyl-CoA decarboxylase

MedGen UID:
91001
Concept ID:
C0342793
Disease or Syndrome
Synonyms: Malonic acidemia; Malonic aciduria; Malonyl-CoA Decarboxylase Deficiency; MCD deficiency
SNOMED CT: Deficiency of malonyl-CoA decarboxylase (124594007); Malonyl-CoA decarboxylase deficiency (124594007); Deficiency of malonyl-coenzyme A decarboxylase (124594007); Malonic aciduria (361203007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): MLYCD (16q23.3)
 
Monarch Initiative: MONDO:0009556
OMIM®: 248360
Orphanet: ORPHA943

Definition

Malonyl-CoA decarboxylase deficiency is an uncommon inherited metabolic disease. The characteristic phenotype is variable, but may include developmental delay in early childhood, seizures, hypotonia, diarrhea, vomiting, metabolic acidosis, hypoglycemia, ketosis, abnormal urinary compounds, lactic acidemia, and hypertrophic cardiomyopathy (Sweetman and Williams, 2001). [from OMIM]

Additional description

From MedlinePlus Genetics
Malonyl-CoA decarboxylase deficiency is a condition that prevents the body from converting certain fats to energy. The signs and symptoms of this disorder typically appear in early childhood. Almost all affected children have delayed development. Additional signs and symptoms can include weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low blood sugar (hypoglycemia). A heart condition called cardiomyopathy, which weakens and enlarges the heart muscle, is another common feature of malonyl-CoA decarboxylase deficiency.  https://medlineplus.gov/genetics/condition/malonyl-coa-decarboxylase-deficiency

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Methylmalonic aciduria
MedGen UID:
343266
Concept ID:
C1855119
Disease or Syndrome
Increased concentration of methylmalonic acid in the urine.
Elevated urine suberic acid level
MedGen UID:
1738538
Concept ID:
C5421685
Finding
The concentration of suberic acid in the urine, normalized for urine concentration, is above the upper limit of normal.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Left ventricular noncompaction cardiomyopathy
MedGen UID:
866782
Concept ID:
C4021133
Disease or Syndrome
Left ventricular non-compaction (LVNC) is characterized by prominent left ventricular trabeculae and deep inter-trabecular recesses. The myocardial wall is often thickened with a thin, compacted epicardial layer and a thickened endocardial layer. In some patients, LVNC is associated with left ventricular dilatation and systolic dysfunction, which can be transient in neonates.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Chronic constipation
MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Pachygyria
MedGen UID:
504794
Concept ID:
CN001193
Finding
Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Ketosis
MedGen UID:
7206
Concept ID:
C0022638
Disease or Syndrome
Presence of elevated levels of ketone bodies in the body.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDeficiency of malonyl-CoA decarboxylase
Follow this link to review classifications for Deficiency of malonyl-CoA decarboxylase in Orphanet.

Recent clinical studies

Etiology

Malvagia S, Papi L, Morrone A, Donati MA, Ciani F, Pasquini E, la Marca G, Scholte HR, Genuardi M, Zammarchi E
Ann Hum Genet 2007 Nov;71(Pt 6):705-12. Epub 2007 May 29 doi: 10.1111/j.1469-1809.2007.00373.x. PMID: 17535268

Diagnosis

Lee SH, Ko JM, Song MK, Song J, Park KS
Mol Genet Genomic Med 2020 Sep;8(9):e1379. Epub 2020 Jun 30 doi: 10.1002/mgg3.1379. PMID: 32602666Free PMC Article
Malvagia S, Papi L, Morrone A, Donati MA, Ciani F, Pasquini E, la Marca G, Scholte HR, Genuardi M, Zammarchi E
Ann Hum Genet 2007 Nov;71(Pt 6):705-12. Epub 2007 May 29 doi: 10.1111/j.1469-1809.2007.00373.x. PMID: 17535268

Therapy

Haan EA, Scholem RD, Croll HB, Brown GK
Eur J Pediatr 1986 Apr;144(6):567-70. doi: 10.1007/BF00496037. PMID: 3709568

Prognosis

Malvagia S, Papi L, Morrone A, Donati MA, Ciani F, Pasquini E, la Marca G, Scholte HR, Genuardi M, Zammarchi E
Ann Hum Genet 2007 Nov;71(Pt 6):705-12. Epub 2007 May 29 doi: 10.1111/j.1469-1809.2007.00373.x. PMID: 17535268

Clinical prediction guides

Lee SH, Ko JM, Song MK, Song J, Park KS
Mol Genet Genomic Med 2020 Sep;8(9):e1379. Epub 2020 Jun 30 doi: 10.1002/mgg3.1379. PMID: 32602666Free PMC Article
Gregg AR, Warman AW, Thorburn DR, O'Brien WE
J Inherit Metab Dis 1998 Jun;21(4):382-90. doi: 10.1023/a:1005302607897. PMID: 9700595

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated C3-DC Acylcarnitine, Malonic Acidemia, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, Malonic Acidemia: Elevated C3-DC, 2022

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