Methylmalonyl-CoA mutase deficiency (MUT)
MUT is inherited in an autosomal recessive pattern. Normally a person has two functional MUT genes. In people with MUT, both genes have a mutation and there is a deficiency of the critical enzyme. Each parent of a newborn with MUT 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 MUT do not typically have symptoms.
The symptoms of MUT in which there is a complete absence of methylmalonyl-CoA mutase usually appear within the first few months of life with the rapid onset of lethargy, vomiting and dehydration. On examination, these babies usually have hypotonia, hepatomegaly and encephalopathy. Laboratory studies done at this point will typically show metabolic acidosis, ketosis and ketonuria, hyperammonemia, and hyperglycemia. If untreated, MUT symptoms may include delayed developmental milestones, chronic renal disease, and pancreatitis. The symptoms of MUT in which there is a partial absence of methylmalonyl-CoA mutase are less severe. They typically present in the first months or years of life with feeding difficulties such as anorexia and vomiting, failure to thrive, hypotonia and developmental delay. These babies may have protein aversion and are at risk for metabolic crises.
- Incidence: MUT has an incidence of approximately 1 in 80,000.
- New York State Method of Screening (First Tier): Screening for MUT is accomplished by measuring the acylcarnitines C3 (propionylcarnitine) and C4DC (methylmalonylcarnitine) by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: Newborn screening cannot distinguish between MUT and propionic acidemia or severe maternal vitamin B12 deficiency.
- 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 MUT are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of MUT.
Diagnostic testing may include urine and plasma organic acid analyses, enzyme analysis and genetic testing of the MUT gene.
Management requires a low-protein diet, as well as carnitine supplementation. Individuals with MUT are not responsive to vitamin B12 therapy. It is recommended that children and adults with MUT should avoid going for long periods without food.
If the low-protein diet is started promptly, most children with MUT have normal growth and development and symptoms are prevented. A delay in treatment can not reverse symptoms that are already present. On treatment, the prognosis for babies diagnosed with MUT is good.
Methylmalonyl-CoA mutase deficiency (MUT) is the most common form of methylmalonic acidemia, a disorder of organic acid metabolism. Methylmalonyl-CoA is a product of the breakdown of several amino acids, as well as some fats and cholesterol. Methylmalonyl-CoA mutase breaks down methylmalonyl-CoA, and this enzyme is made by the MUT gene. Mutations in this gene cause partial or complete absence of methylmalonyl-CoA mutase, resulting in accumulation of methylmalonic acid and other damaging substances.