Methylmalonyl-CoA mutase deficiency

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
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Methylmalonyl-CoA mutase deficiency
Synonyms	MUT deficiency
Pronounce	N/A
Specialty	N/A
Symptoms	Metabolic acidosis, failure to thrive, developmental delay
Complications	Neurological damage, renal failure
Onset	Infancy
Duration	Chronic
Types	MUT0, MUT-
Causes	Genetic mutation in the MUT gene
Risks	Consanguinity, family history
Diagnosis	Genetic testing, metabolic screening
Differential diagnosis	Propionic acidemia, methylmalonic acidemia
Prevention	Genetic counseling
Treatment	Dietary management, cobalamin supplementation
Medication	Hydroxocobalamin, L-carnitine
Prognosis	Variable, depends on type and treatment
Frequency	Rare, estimated 1 in 50,000 to 100,000
Deaths	Can be fatal if untreated

Methylmalonyl-CoA mutase deficiency is a rare metabolic disorder that affects the body's ability to break down certain proteins and fats. It is a type of organic acidemia and is caused by a deficiency in the enzyme methylmalonyl-CoA mutase (MUT), which is crucial for the metabolism of certain amino acids and lipids.

Pathophysiology

Methylmalonyl-CoA mutase is an enzyme that catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA, a critical step in the degradation of certain amino acids, such as valine, isoleucine, methionine, and threonine. This reaction is part of the citric acid cycle, which is essential for energy production in cells. In individuals with methylmalonyl-CoA mutase deficiency, the enzyme is either absent or not functioning properly, leading to the accumulation of methylmalonic acid and other toxic substances in the body. This accumulation can cause a variety of symptoms and complications, including metabolic acidosis, developmental delay, and organ damage.

Clinical Presentation

The clinical presentation of methylmalonyl-CoA mutase deficiency can vary widely among affected individuals. Symptoms may appear in the neonatal period or later in life, depending on the severity of the enzyme deficiency. Common symptoms include:

• Poor feeding
• Vomiting
• Lethargy
• Hypotonia
• Developmental delay
• Failure to thrive
• Metabolic acidosis

Diagnosis

Diagnosis of methylmalonyl-CoA mutase deficiency is typically made through a combination of clinical evaluation, biochemical testing, and genetic analysis. Elevated levels of methylmalonic acid in the blood and urine are indicative of the disorder.

Treatment

Treatment for methylmalonyl-CoA mutase deficiency often involves dietary management to limit the intake of certain amino acids that cannot be properly metabolized. In some cases, vitamin B12 (cobalamin) supplementation may be beneficial, particularly in patients with a cobalamin-responsive form of the disorder.

Complications

If left untreated, methylmalonyl-CoA mutase deficiency can lead to serious complications, including:

• Neurological damage
• Chronic kidney disease
• Pancreatitis
• Cardiomyopathy

See also

• Organic acidemia
• Metabolic disorder
• Amino acid metabolism
• Citric acid cycle

The urea cycle, related to amino acid metabolism.

See Also

• Propionic acidemia
• Isovaleric acidemia
• Maple syrup urine disease