methylmalonic acidemia

Methylmalonic acidemia (MMA) is a group of inherited disorders that prevent the body from breaking down proteins and fats (lipids) properly [1]. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to life-threatening [1].

This condition is characterized by an abnormally high level of acid in the blood (acidemia) and body tissues, resulting from the inability to metabolize proteins and fats [2]. Infants with this condition typically have symptoms such as vomiting, dehydration, weak muscle tone (hypotonia), and other complications [3].

MMA can also cause a buildup of acids and other harmful substances in the blood, urine, and other cells, including brain cells [4]. This can lead to severe health issues, including seizures and stroke [5].

It's essential to diagnose MMA as quickly as possible since affected individuals are often very ill, and untreated decompensations can worsen long-term complications [6].

References: [1] Context 1: Description. Methylmalonic acidemia is a group of inherited disorders that prevent the body from breaking down proteins and fats (lipids) properly. [2] Context 2: Methylmalonic acidemia (MMA) is a group of genetic disorders in which the body can’t breakdown (metabolize) proteins and fats properly. [3] Context 1: Affected infants can experience vomiting, dehydration, weak muscle tone (hypotonia ... [4] Context 4: People with this condition are unable to produce an enzyme that is needed to break down and use certain proteins and fats found in food. This causes a buildup of acids and other harmful substances in the blood, urine and other cells, including brain cells. [5] Context 13: Symptoms include seizures and stroke. [6] Context 15: It’s essential to diagnose MMA as quickly as possible since affected individuals are often very ill, and untreated decompensations can worsen long-term complications.

Methylmalonic acidemia (MMA) is a rare genetic disorder that affects the body's ability to break down certain amino acids, leading to the accumulation of toxic substances in the body.

Common Signs and Symptoms:

• Weak muscle tone (hypotonia): People with MMA often have weak muscles, which can lead to poor feeding and loss of appetite [5].
• Lethargy: Excessive tiredness or lethargy is a common symptom of MMA, especially in infants [2][6].
• Vomiting: Vomiting is another frequent symptom of MMA, which can lead to dehydration if not treated promptly [2][3].
• Seizures: Seizures are also a possible symptom of MMA, particularly in severe cases [3][5].
• Intellectual disability: Some people with MMA may experience intellectual disability or developmental delays [4][8].

Other Possible Symptoms:

• Poor appetite and growth: People with MMA may have poor appetite and fail to thrive due to their weakened state [9].
• Eye abnormalities: Eye problems, such as vision impairment, are also possible in individuals with MMA [5].
• Kidney problems: Osteoporosis and kidney stones are potential complications of MMA [4].

Early Warning Signs:

• Failure to thrive: Infants with MMA may fail to gain weight or grow at a normal rate due to their weakened state [6].
• Hepatosplenomegaly: Enlargement of the liver and spleen can be an early sign of MMA [6].

It's essential to note that these symptoms can vary in severity and presentation, depending on the individual case. If you suspect someone has methylmalonic acidemia, it's crucial to consult a medical professional for proper diagnosis and treatment.

References: [1] Not provided (since there is no relevant information) [2] May 17, 2024 [3] Symptoms · Poor feeding and loss of appetite · Vomiting · Weak muscle tone (hypotonia) · Lack of energy (lethargy) · Seizures · Coma. [4] Oct 11, 2022 [5] May 16, 2023 [6] Sep 19, 2022 [7] Apr 20, 2012 [8] by T Chen · 2023 · Cited by 23 — The clinical symptoms of early onset MMA are mainly neuropsychiatric injury, common developmental lag, abnormal mental behavior, hydrocephalus, epilepsy and so ... [9] Some of the first symptoms of a metabolic crisis. Symptoms of a metabolic crisis are poor appetite, nausea, vomiting, diarrhea, extreme sleepiness, irritable ...

Methylmalonic acidemia (MMA) can be diagnosed through various diagnostic tests, which are essential for early detection and management of the condition.

• Newborn screening test: This is a primary method for detecting isolated methylmalonic acidemia in newborns. The test measures the levels of propionylcarnitine (C3) on dried blood spots.
• Blood tests: Blood samples can be used to measure the levels of methylmalonic acid (MMA) and other metabolites, such as homocysteine and methionine. Elevated levels of MMA in the blood are indicative of MMA.
• Urine tests: Urine tests can also detect elevated levels of MMA, which is a key indicator of MMA.
• Genetic testing: Genetic testing can verify the diagnosis of MMA by identifying mutations in the MUT gene or other genes associated with the condition.

According to [1], the standard newborn screening tests sometimes provide the diagnosis of methylmalonic acidemia. However, not all places test for this specific disease, and infants might first experience symptoms before the results of these screening tests are available.

In addition to these diagnostic tests, a thorough medical history and exam are also essential for diagnosing MMA [2].

References: [1] Context result 2 [2] Context result 3

Treatment Options for Methylmalonic Acidemia

Methylmalonic acidemia (MMA) is a rare genetic disorder that affects the body's ability to break down certain amino acids and fats, leading to an accumulation of toxic substances in the blood. While there is no cure for MMA, various treatment options are available to manage the condition.

Medications Used to Treat MMA

Several medications have been used to treat MMA, including:

• Cobalamin (Vitamin B12): Given as an injection, cobalamin therapy has been shown to significantly improve methylmalonyl-CoA mutase activity in patients with cobalamin-responsive MMA [8].
• Levo-carnitine (L-carnitine): A dietary supplement that is also used to treat all patients with methylmalonic acidemia, who apparently have a deficiency of this essential nutrient [2].
• Cobalamin and carnitine: Medication treatment consists of cobalamin given as an injection, carnitine, and antibiotics [9].

Investigational Therapies

Recent studies have explored the use of investigational therapies for MMA, including:

• mRNA-3705: An investigational therapeutic for methylmalonic acidemia (MMA) due to methylmalonyl-CoA mutase (MUT) deficiency [7].
• Other treatments: Various other treatments are being investigated, but more research is needed to determine their efficacy and safety.

Importance of Early Diagnosis and Treatment

Early diagnosis and treatment of MMA can significantly improve outcomes for patients. It is essential for individuals with a family history of the condition or those who exhibit symptoms to consult a healthcare provider for proper evaluation and management.

References:

[2] Levo-carnitine (L-carnitine) is a dietary supplement that is also used to treat all patients with methylmalonic acidemia, who apparently have a deficiency of this essential nutrient. [8] Cobalamin therapy significantly improves methylmalonyl-CoA mutase activity in patients with cobalamin-responsive MMA. [9] Medication treatment consists of cobalamin given as an injection, carnitine, and antibiotics.

Methylmalonic acidemia (MMA) is a group of genetic disorders that can be challenging to diagnose due to its similarity with other metabolic and nutritional deficiency states. The differential diagnosis of MMA includes several conditions that need to be ruled out before making an accurate diagnosis.

Conditions to Consider:

• Acquired vitamin B12 deficiency: This condition can also lead to elevated methylmalonic acid levels in the blood, similar to MMA.
• Vitamin B12-responsive methylmalonic aciduria: Some cases of MMA may respond to vitamin B12 supplementation, making it essential to consider this condition in the differential diagnosis.
• Homocystinuria without methylmalonic acidemia: This condition is characterized by elevated homocysteine levels but normal methylmalonic acid levels. It can be a differential diagnosis for MMA.
• Combined malonic and methylmalonic aciduria: This rare genetic disorder involves the accumulation of both malonic and methylmalonic acids in the body, making it a potential differential diagnosis for MMA.

Other Conditions to Consider:

• Mitochondrial DNA depletion syndrome: This condition can also lead to elevated levels of organic acids, including methylmalonic acid.
• Transcobalamin receptor deficiency: This rare genetic disorder affects the body's ability to absorb vitamin B12, which can lead to elevated methylmalonic acid levels.

Key Points:

• A definitive diagnosis of MMA is based on urine organic acid analysis using gas chromatography/mass spectrometry (GC/MS) [1].
• The differential diagnosis of MMA includes several conditions that need to be ruled out before making an accurate diagnosis.
• Vitamin B12 deficiency and homocystinuria without methylmalonic acidemia are two common conditions that can be considered in the differential diagnosis of MMA.

References:

[1] A definitive diagnosis of the disorder is based on urine organic acid analysis using gas chromatography/mass spectrometry (GC/MS) [6, 7]. [2] Differential Diagnoses · Combined malonic and methylmalonic aciduria · Genetics of Propionic Acidemia (Propionyl CoA Carboxylase Deficiency). [3] Oct 12, 2023 — Combined malonic and methylmalonic aciduria · Nutritional vitamin B12 deficiency · Mitochondrial DNA depletion syndrome · Transcobalamin receptor ... [4] Sep 8, 2022 — Isolated methylmalonic acidemia refers to a group of inborn errors of metabolism associated with elevated methylmalonic acid (MMA) concentration in the blood ... [5] Sep 19, 2022 — Diagnosis of Methylmalonic Acidemia · Cyanotic heart disease · Diabetes mellitus · Endocarditis · Ehlers-Danlos syndrome · Marfan syndrome. [6] May 17, 2024 — Methylmalonic acidemia (MMA) is a group of genetic disorders in which the body can't breakdown (metabolize) proteins and fats properly. This ... [7] The differential diagnosis of this disease includes other metabolic and nutritional deficiency states, such as acrodermatitis enteropathica, other ...