methylmalonic aciduria and homocystinuria type cblG

Methylmalonic aciduria and homocystinuria type cblG, also known as MACHC, is a rare genetic disorder that affects the body's ability to process certain amino acids, fatty acids, and cholesterol. This condition is characterized by the accumulation of methylmalonic acid and homocysteine in the blood, which can lead to various health problems.

Key Features:

• Metabolic Disorder: MACHC is a metabolic disorder that affects the body's ability to convert certain amino acids, fatty acids, and cholesterol.
• Methylmalonic Acid Accumulation: The condition leads to the accumulation of methylmalonic acid in the blood, which can cause various health problems.
• Homocysteine Buildup: MACHC also causes a buildup of homocysteine in the blood, which can lead to cardiovascular and neurological issues.

Symptoms:

• Megaloblastic Anemia: People with MACHC often experience megaloblastic anemia, characterized by large red blood cells.
• Lethargy and Failure to Thrive: The condition can cause lethargy and failure to thrive in infants and young children.
• Developmental Delay: MACHC may also lead to developmental delay and intellectual deficit in some individuals.

Causes:

• Genetic Mutation: MACHC is caused by a genetic mutation in the MMACHC gene, which codes for an enzyme involved in vitamin B12 metabolism.
• Inherited Disorder: The condition is

Based on the search results, here are the signs and symptoms of methylmalonic aciduria and homocystinuria type cblG:

Common Features:

• Feeding difficulties [5]
• Lethargy [5]
• Seizures [5]
• Poor muscle tone (hypotonia) [5]
• Developmental delay [3, 5]
• Microcephaly (unusually small head size) [5]

Neurological Problems:

• Weak muscle tone (hypotonia) [1]
• Seizures [1, 5]
• Cognitive decline [4]
• Unsteady gait [4]
• Myelopathy [4]
• Behavioral problems [4]

Other Symptoms:

• Failure to thrive [2, 9]
• Recurrent vomiting [7]
• Progressive failure to thrive [7]
• Metabolic crises [7]

These symptoms can develop in infancy or at any age and are a result of the body's inability to properly metabolize vitamin B12 (cobalamin) due to the cblG mutation. It is essential for early diagnosis and treatment to prevent long-term complications.

References: [1] - Context 1 [2] - Context 2 [3] - Context 3 [4] - Context 4 [5] - Context 5 [7] - Context 7 [9] - Context 9

Based on the search results, it appears that there are several diagnostic tests available for methylmalonic aciduria and homocystinuria type cblG.

• Methylmalonic Aciduria and Homocystinuria testing by sequencing of the following genes: This test involves sequencing the genes ABCD4, ACSF3, AMN, CBS, CD320, CUBN, GIF, IVD, LMBRD1, MCEE, MLYCD, MMAA, and MMAB to identify pathogenic variants associated with methylmalonic aciduria and homocystinuria type cblG [4].
• Exome-based NextGen sequencing with CNV analysis: This is a favored testing approach for diagnosing methylmalonic aciduria and homocystinuria type cblG, as it allows for cost-effective reflexing to PGxome or other exome-based testing [5].
• Enzyme analysis of fibroblasts: Definitive diagnosis of methylmalonic aciduria and homocystinuria type cblG is made after enzyme analysis of fibroblasts in search of the specific enzyme abnormality [6].
• Complete blood cell (CBC) counts: CBC counts may also be performed to identify any abnormalities that could indicate methylmalonic aciduria and homocystinuria type cblG [6].

It's worth noting that neonatal screening has allowed for prompt identification of the disease by detection of elevated propionylcarnitine (C3) and low methionine on mass spectrometry-based testing [8]. Molecular testing is also used to confirm suspected cobalamin/propionate/homocysteine metabolism-related disorders in individuals with clinical symptoms and/or laboratory findings [9].

References: [4] - Methylmalonic Aciduria and Homocystinuria testing by sequencing of the following genes: ABCD4, ACSF3, AMN, CBS, CD320, CUBN, GIF, IVD, LMBRD1, MCEE, MLYCD, MMAA ... [5] - Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based ... [6] - Sep 19, 2022 — Definitive diagnosis is made after enzyme analysis of fibroblasts in search of the specific enzyme abnormality. Complete blood cell (CBC) counts ... [8] - by S Kalantari · 2022 · Cited by 25 — Neonatal screening has allowed prompt identification of the disease by detection of elevated propionylcarnitine (C3) and low methionine on mass ... [9] - Aug 22, 2023 — Molecular testing is used to confirm suspected cobalamin/propionate/homocysteine metabolism-related disorders in individuals with clinical symptoms and/or ...

Methylmalonic aciduria and homocystinuria type cblG is a rare genetic disorder that affects the body's ability to process certain amino acids, fatty acids, and cholesterol. The condition is caused by a deficiency in the enzyme methylmalonyl-CoA mutase.

Treatment Overview

The primary goal of treatment for methylmalonic aciduria and homocystinuria type cblG is to manage symptoms and prevent complications. While there is no cure for this disorder, various treatments can help alleviate its effects.

• Vitamin B12 supplementation: Regular doses of hydroxycobalamin (vitamin B12) are essential in treating methylmalonic aciduria and homocystinuria type cblG [8]. This vitamin helps convert methylmalonyl-CoA to succinyl-CoA, thereby reducing the accumulation of toxic compounds.
• Folate supplementation: Some individuals with this disorder may also require folate supplementation to help reduce homocysteine levels [8].
• Betaine supplementation: Betaine has been shown to be effective in reducing homocysteine levels and improving symptoms in some cases [9].

Other Considerations

In addition to vitamin B12, folate, and betaine supplementation, other treatments may be necessary to manage specific symptoms or complications. These can include:

• Volume replacement: In cases of severe metabolic acidosis, volume replacement with isotonic solutions containing high glucose levels may be required [4].
• Levo-carnitine (L-carnitine) supplementation: L-carnitine has been used to treat patients with methylmalonic acidemia, including those with cblG type [5].

Importance of Early Diagnosis and Treatment

Early diagnosis and treatment are crucial in managing the symptoms and preventing complications associated with methylmalonic aciduria and homocystinuria type cblG. Regular monitoring and follow-up care can help ensure that individuals with this disorder receive the necessary support to manage their condition effectively.

References:

[4] Ozempic Could Help Curb Alcoholism. [5] Dionisi‐Vici C, Deodato F, Röschinger W, Rhead W, Wilcken B. ‘Classical’ organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long‐term outcome and effects of expanded newborn screening using tandem mass spectrometry. [8] Cerner Multum Consumer Drug Information. [9] A drug is a chemical substance that produces a biological effect when administered to a living organism.

Differential Diagnosis of Methylmalonic Aciduria and Homocystinuria Type CblG

Methylmalonic aciduria and homocystinuria type cblG is a condition characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, and other systemic symptoms. When diagnosing this condition, it's essential to consider the differential diagnosis, which includes:

• Multiple Sclerosis: This form of homocystinuria without methylmalonic aciduria can be distinguished on the basis of clinical presentation and laboratory findings [6].
• Cyanotic Heart Disease: A congenital heart defect that can present with similar symptoms to methylmalonic aciduria and homocystinuria type cblG.
• Diabetes Mellitus: Uncontrolled diabetes can lead to megaloblastic anemia, which may be mistaken for methylmalonic aciduria and homocystinuria type cblG.
• Endocarditis: A bacterial infection of the heart valves that can cause systemic symptoms similar to those seen in methylmalonic aciduria and homocystinuria type cblG.
• Ehlers-Danlos Syndrome: A genetic disorder affecting connective tissue that can present with similar musculoskeletal symptoms to methylmalonic aciduria and homocystinuria type cblG.
• Marfan Syndrome: A genetic disorder affecting the body's connective tissue that can cause systemic symptoms similar to those seen in methylmalonic aciduria and homocystinuria type cblG.

It's crucial to note that differential diagnosis of methylmalonic aciduria includes acquired cobalamin depletion or inherited cobalamin deficiencies, transient mild methylmalonic acidurias, and other conditions [10].

References:

[6] - The forms of homocystinuria without methylmalonic aciduria can be distinguished on the basis of clinical presentation and laboratory findings. [8] - Diagnosis of Methylmalonic Acidemia · Cyanotic heart disease · Diabetes mellitus · Endocarditis · Ehlers-Danlos syndrome · Marfan syndrome. [10] - Differential diagnosis of methylmalonic aciduria is acquired cobalamin depletion or inherited cobalamin deficiencies, transient mild methylmalonic acidurias ...