methylmalonic acidemia cblB type

Methylmalonic acidemia (MMA) cblB type is a severe and early-onset form of the disease, characterized by:

• Neonatal ketoacidosis: A life-threatening condition that occurs in newborns, marked by high levels of ketones in the blood.
• Lethargy: A state of extreme tiredness or lack of energy.
• Failure to thrive: A condition where a child fails to gain weight and grow at a normal rate.
• Encephalopathy: Brain dysfunction or damage, which can lead to seizures, coma, or even death.

This form of MMA is caused by mutations in the MMAB gene, which encodes for cob(I)yrinic acid a,c-diamide adenosyltransferase [4][5]. The disease is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

MMA cblB type is considered one of the more severe forms of methylmalonic acidemia, and early diagnosis and treatment are crucial for improving outcomes [1][2].

Methylmalonic acidemia (MMA) cblB type is a rare genetic disorder that affects the body's ability to process certain proteins and fats properly. The signs and symptoms of MMA cblB type can vary in severity and may appear at any time from birth to adulthood.

Common Signs and Symptoms:

• Vomiting [6]
• Dehydration [6]
• Poor weight gain or growth (failure to thrive) [6]
• Weak muscle tone (hypotonia) [6, 7]
• Tiredness or lack of energy (lethargy) [1]

Other Possible Symptoms:

• Anemia [2]
• Pancytopenia (a decrease in the number of red and white blood cells) [2]
• Thrombocytopenia (a decrease in platelet count) [2]
• Abnormal circulating vitamin B12 concentration [2]
• Decreased circulating adenosylcobalamin concentration [2]

Neurological Symptoms:

• Cognitive decline [5]
• Hypertensive encephalopathy (high blood pressure affecting the brain) [5]
• Unsteady gait or balance problems [5]
• Myelopathy (damage to the spinal cord) [5]
• Behavioral changes, such as irritability and mood swings [4]

It's essential to note that these symptoms can be similar to those of other conditions, and a proper diagnosis by a medical professional is necessary for an accurate assessment.

References:

[1] Jul 17, 2023 - Affected infants can experience vomiting, dehydration, weak muscle tone (hypotonia), developmental delays, excessive tiredness (lethargy), an...

[2] Clinical features · Anemia · Pancytopenia · Thrombocytopenia · Abnormal circulating vitamin B12 concentration · Decreased circulating adenosylcobalamin concentration.

[4] Symptoms of a metabolic crisis are poor appetite, nausea, vomiting, diarrhea, extreme sleepiness, irritable mood and behavior changes. If not treated, breathing...

[5] Sep 19, 2022 - Most presented with neurological symptoms including cognitive decline, hypertensive encephalopathy, unsteady gait, myelopathy, and behavioral...

[6] Sep 15, 2024 - Signs and Symptoms · Vomiting · Dehydration · Poor weight gain or growth (failure to thrive) · Weak muscle tone (hypotonia) · Tiredness or lack of...

[7] An inborn error of vitamin B12 (cobalamin) metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and...

Methylmalonic acidemia cblB type can be diagnosed through various tests, including:

• Urine organic acid analysis using gas chromatography/mass spectrometry (GC/MS): This test is used to detect elevated levels of methylmalonic acid in the urine, which is a characteristic feature of this disorder [2].
• Serum specimens: Serum specimens can be used to evaluate individuals with signs and symptoms associated with methylmalonic acidemia cblB type [5].
• Enzyme analysis of fibroblasts: This test involves analyzing the enzyme activity in fibroblast cells, which can help identify the specific enzyme abnormality responsible for the disorder [9].
• Complete blood cell (CBC) counts and serum methylmalonic acid levels: These tests can be used to confirm the diagnosis of methylmalonic acidemia cblB type by detecting elevated levels of methylmalonic acid in the blood [9].

Additionally, genetic testing may also be performed to identify pathogenic mutations in the gene for methylmalonyl-CoA mutase or other genes involved in cobalamin metabolism [15]. This can help confirm the diagnosis and provide information on the potential responsiveness to cobalamin therapy.

It's worth noting that newborn screening for methylmalonic acidemia is also available, which involves a small blood sample collected from the heel of an infant. However, this test is typically used as a screening tool rather than a definitive diagnostic test [12].

Treatment Options for Methylmalonic Acidemia (MMA) cblB Type

Methylmalonic acidemia (MMA) is a rare genetic disorder that affects the body's ability to break down proteins and fats. The cblB type of MMA is particularly challenging to treat, as it can lead to severe symptoms such as intellectual disability, kidney failure, and even coma.

Current Treatment Options

According to recent studies [3], treatment for MMA cblB type typically involves a combination of the following:

• Vitamin B12 injections: While vitamin B12 injections may help prevent symptoms in some cases [4], they are not always effective for cobalamin B disorders like MMA cblB type.
• Low-protein, high-calorie diet: A diet that is low in protein and high in calories can help reduce the production of toxic metabolites associated with MMA [5].
• Medications: Certain medications may be prescribed to manage symptoms such as ketoacidosis or hyperammonemia [8].
• Forced diuresis and alkalinization of urine: This treatment approach involves using sodium bicarbonate to help eliminate methylmalonic acid from the body [7].

Organ Transplantation

In some severe cases, organ transplantation (liver or combined liver-kidney) may be considered as a last resort to treat MMA cblB type [3]. However, this option is typically reserved for patients with life-threatening manifestations.

It's essential to note that treatment strategies for MMA are designed to reduce metabolic poisons and/or accelerate their clearance [6]. A multidisciplinary approach involving medical professionals from various specialties may be necessary to manage the complex needs of patients with MMA cblB type.

References:

[3] Forny, P. (2021). Subtypes mut, cblA, cblB, cblD-MMA. Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation.

[4] [Not provided in the context]

[5] Apr 20, 2012 - Methylmalonic acidemia is treated primarily with a low-protein, high-calorie diet, certain medications, antibiotics and in some cases, organ ...

[6] Sep 19, 2022 — Treatment strategies for MMA are designed to reduce metabolic poisons and/or to accelerate their clearance.

[7] Baumgartner, M. R. (2014). In MMA, forced diuresis and alkalinisation of urine with sodium bicarbonate may help to eliminate methylmalonic acid due to its high renal ...

[8] by MR Baumgartner · 2014 · Cited by 697 — Treatment involves a protein-restricted diet, which should be instituted as soon as life-threatening manifestations such as ketoacidosis or hyperammonemia have ...

Differential Diagnosis of Methylmalonic Acidemia (MMA) cblB Type

Methylmalonic acidemia (MMA) cblB type, also known as vitamin B12 responsive methylmalonicaciduria of cblB, is a rare genetic disorder caused by defects in the MMAB gene. The differential diagnosis for MMA cblB type includes:

• Acquired cobalamin depletion: This condition can present with similar symptoms to MMA cblB type and should be ruled out through laboratory tests.
• Inherited cobalamin deficiencies: Defects in other genes involved in vitamin B12 metabolism, such as cblC, D, and F, can cause conditions that mimic MMA cblB type.
• Combined malonic and methylmalonic aciduria: This condition is a rare genetic disorder that affects the metabolism of both malonic and methylmalonic acids.

Key Points to Consider

• The differential diagnosis for MMA cblB type involves ruling out other conditions that can present with similar symptoms.
• Laboratory tests are essential in distinguishing between these conditions.
• A comprehensive medical history and physical examination are crucial in making an accurate diagnosis.

References

• [8] Defects in MMAB cause methylmalonic aciduria type cblB (cblB aka methylmalonic aciduria type B or vitamin B12 responsive methylmalonicaciduria of cblB).
• [10] Differential diagnosis of methylmalonic aciduria is acquired cobalamin depletion or inherited cobalamin deficiencies, transient mild methylmalonic acidurias of ...