HomeGeneticsConditionCombined malonic and methylmalonic aciduria
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Combined malonic and methylmalonic aciduria
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Combined malonic and methylmalonic aciduria

Combined malonic and methylmalonic aciduria (CMAMMA) is a rare genetic condition characterized by the buildup of malonic and methylmalonic acids in the body.

Overview

Combined malonic and methylmalonic aciduria (CMAMMA) is a condition characterized by high levels of certain chemicals, known as malonic acid and methylmalonic acid, in the body. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although both are elevated.

Symptoms

The signs and symptoms of CMAMMA can begin in childhood or adulthood:

  • Childhood onset: Buildup of acids can cause the blood to become too acidic (ketoacidosis), which can damage tissues and organs. Other symptoms include involuntary muscle tensing (dystonia), weak muscle tone (hypotonia), developmental delay, failure to thrive, low blood glucose (hypoglycemia), coma, and an unusually small head size.
  • Adulthood onset: Individuals may experience neurological problems, such as seizures, loss of memory, a decline in thinking ability, or psychiatric diseases.

Frequency

CMAMMA appears to be a rare disease, with approximately a dozen cases reported in the scientific literature.

Causes

Mutations in the ACSF3 gene cause CMAMMA. This gene provides instructions for making an enzyme that plays a role in the formation of fatty acids. The ACSF3 enzyme acts as a malonyl-CoA synthetase and a methylmalonyl-CoA synthetase. Researchers suspect that mutations lead to altered enzymes with little or no function, causing malonic and methylmalonic acids to build up in the body.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. Parents of an affected individual typically carry one copy of the mutated gene but do not show signs or symptoms of the condition.

Frequently Asked Questions

Sequencing of the ACSF3 gene is the primary test; it can be done on a blood sample taken after a short fast to avoid post‑prandial interference. If a variant is found, a second sample may be requested for confirmation. Some labs also use multiplex ligation‑dependent probe amplification (MLPA) to detect larger deletions or duplications.
CMAMMA is autosomal recessive, so both parents are carriers. For future pregnancies, carrier testing of the partner is recommended. Prenatal diagnosis can be performed via chorionic villus sampling (10–12 weeks) or amniocentesis (15–18 weeks) to analyze the fetus’s ACSF3 gene. Preimplantation genetic testing (PGT) during IVF is another option to select unaffected embryos.
Look for sudden vomiting, lethargy, rapid breathing, low blood sugar, or a sweet‑smelling breath that may indicate ketoacidosis. If any of these appear, call emergency services right away, bring the child to the nearest hospital, and have the parents give a quick glucose drink or gel if the child can swallow. Early treatment with IV fluids, glucose, and electrolytes can prevent organ damage.
metabolic dietitian may recommend limiting foods high in methionine and certain fats, while ensuring adequate protein from low‑methionine sources. Some patients benefit from a low‑protein, high‑carbohydrate diet, but the exact plan should be individualized and monitored for growth and blood chemistry. Supplements such as carnitine or vitamin B12 are usually not needed unless a deficiency is documented.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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