MA is inherited in an autosomal recessive pattern. Normally a person has two functional MLYCD genes. In people with MA, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with MA typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of MA do not typically have symptoms.
There are two forms of MA, neonatal-onset and late-onset. Some patients patients diagnosed by expanded newborn screening have remained asymptomatic.
Neonatal-onset: The neonatal-onset form of this disorder is more severe and symptoms typically begin in the first few days of life. Symptoms include lethargy, low muscle tone, enlarged liver and cardiomyopathy (heart muscle disease).
Late-onset: Episodes in late-onset MA may be brought on by illness. Long-term symptoms include developmental delay, low muscle tone and cardiomyopathy (heart muscle disease).
- Incidence: MA is rare, with less than 30 cases reported in the literature.
- New York State Method of Screening (First Tier): Screening for MA is accomplished by measuring the acylcarnitine C3DC by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: None known
- Interpretation/reporting of data: Results are reported as screen negative, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for MA are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of MA.
Diagnostic testing may include urine organic acid analysis, total and free carnitine, MLYCD gene sequencing and MLYCD enzyme activity analysis.
There is not a standard treatment protocol. Supplementation with carnitine or dietary management including careful monitoring of fat intake may be helpful.
Prognosis is not well known because MA is rare.
Malonic aciduria (MA) is a disorder of organic acid metabolism (inherited metabolic disorder). MA is caused by mutations in the MLYCD gene.