Methylmalonyl-CoA mutase deficiency: Difference between revisions

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

Latest revision as of 04:19, 8 April 2025

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
W8MD medical weight loss NYC and sleep center NYC

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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

Neurological damage
Chronic kidney disease
Pancreatitis
Cardiomyopathy

@@ Line 1: / Line 1: @@
-'''Methylmalonyl-CoA mutase deficiency''' is a rare [[genetic disorder]] that affects the body's ability to metabolize certain proteins and fats. This condition is also known as '''Methylmalonic Acidemia''' or '''MMA''' for short. It is an [[inborn error of metabolism]] that can lead to a variety of health problems, including developmental delay, failure to thrive, and life-threatening metabolic crises.
+{{SI}}
+{{Infobox medical condition
-==Causes==
+| name                    = Methylmalonyl-CoA mutase deficiency
-Methylmalonyl-CoA mutase deficiency is caused by mutations in the [[MUT gene]]. This gene provides instructions for making an enzyme called methylmalonyl-CoA mutase. This enzyme is involved in the breakdown of certain [[amino acids]] and [[lipids]]. Mutations in the MUT gene reduce or eliminate the activity of this enzyme, which disrupts the normal breakdown of these substances and leads to a buildup of a substance called methylmalonic acid in the body.
+| image                   = [[File:Protein_MUT_PDB_2XIJ.png|250px]]
+| caption                 = Structure of the [[Methylmalonyl-CoA mutase]] enzyme
-==Symptoms==
+| synonyms                = MUT deficiency
-The symptoms of Methylmalonyl-CoA mutase deficiency can vary widely, but they often appear in the first year of life. They may include:
+| field                   = [[Medical genetics]]
+| symptoms                = [[Metabolic acidosis]], [[failure to thrive]], [[developmental delay]]
-* [[Failure to thrive]]
+| complications           = [[Neurological damage]], [[renal failure]]
-* [[Developmental delay]]
+| onset                   = [[Infancy]]
-* [[Vomiting]]
+| duration                = [[Chronic]]
-* [[Dehydration]]
+| types                   = [[MUT0]], [[MUT-]]
-* [[Lethargy]]
+| causes                  = [[Genetic mutation]] in the [[MUT gene]]
-* [[Seizures]]
+| risks                   = [[Consanguinity]], [[family history]]
-* [[Coma]]
+| diagnosis               = [[Genetic testing]], [[metabolic screening]]
+| differential            = [[Propionic acidemia]], [[methylmalonic acidemia]]
-In severe cases, the condition can lead to life-threatening metabolic crises.
+| prevention              = [[Genetic counseling]]
+| treatment               = [[Dietary management]], [[cobalamin supplementation]]
-==Diagnosis==
+| medication              = [[Hydroxocobalamin]], [[L-carnitine]]
-Methylmalonyl-CoA mutase deficiency is typically diagnosed through [[newborn screening]] tests. These tests look for elevated levels of methylmalonic acid in the blood or urine. If these levels are high, additional genetic testing may be done to confirm the diagnosis.
+| prognosis               = Variable, depends on type and treatment
+| frequency               = Rare, estimated 1 in 50,000 to 100,000
-==Treatment==
+| deaths                  = Can be fatal if untreated
-There is currently no cure for Methylmalonyl-CoA mutase deficiency. Treatment is focused on managing the symptoms and preventing metabolic crises. This may involve a special diet low in certain proteins and fats, medications to reduce the levels of methylmalonic acid in the body, and in some cases, [[organ transplantation]].
+}}
+'''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.
-==Prognosis==
+== Pathophysiology ==
-The prognosis for individuals with Methylmalonyl-CoA mutase deficiency varies. Some individuals may have a mild form of the condition and live into adulthood with appropriate management, while others may have a severe form of the condition and experience life-threatening metabolic crises.
+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]]
+[[File:Urea_cycle_2.png|left|thumb|The urea cycle, related to amino acid metabolism.]]
+== See Also ==
+* [[Propionic acidemia]]
+* [[Isovaleric acidemia]]
+* [[Maple syrup urine disease]]
+{{Metabolic disorders}}
 [[Category:Genetic disorders]]
 [[Category:Metabolic disorders]]
 [[Category:Rare diseases]]
-{{medicine-stub}}