methylmalonic aciduria and homocystinuria type cblD

Methylmalonic Aciduria and Homocystinuria Type CblD: A Rare Genetic Disorder

Methylmalonic aciduria and homocystinuria type cblD (MAHCD) is a rare autosomal recessive disorder of cobalamin (cbl; vitamin B12) metabolism. This condition affects the body's ability to process certain protein building blocks (amino acids), fat building blocks (fatty acids), and cholesterol, leading to a combination of features from different metabolic disorders.

Key Features:

• Inherited Condition: MAHCD is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Cobalamin Metabolism Disorder: The disorder affects the metabolism of cobalamin (vitamin B12), which is essential for hematologic and neurologic function.
• Amino Acid Processing Deficiency: Individuals with MAHCD have a deficiency in processing certain amino acids, leading to an accumulation of methylmalonic acid and homocysteine in the body.
• Variable Biochemical, Neurological, and Hematological Manifestations: The condition is characterized by variable biochemical, neurological, and hematological manifestations, including delayed growth, small head size, skin rash, vomiting, poor appetite, diarrhea, fever, sleeping longer or more often.

Genetic Heterogeneity:

MAHCD is a genetically heterogeneous disorder, meaning that it can be caused by mutations in different genes. The MMADHC gene on chromosome 2q23 has been identified as the cause of isolated methylmalonic aciduria cblD type (MACD) and combined methylmalonic aciduria and homocystinuria cblD type.

References:

• [1] Description. Methylmalonic aciduria (MMA) and homocystinuria type cblD (MAHCD) is an autosomal recessive disorder of cobalamin (cbl; vitamin B12) metabolism.
• [9] Methylmalonic aciduria (MMA) and homocystinuria type cblD (MAHCD) is an autosomal recessive disorder of cobalamin (cbl; vitamin B12) metabolism.
• [13] Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous metabolic disorder of cobalamin (cbl; vitamin B12) metabolism, which is essential for hematologic and neurologic function.

Note: The references provided are based on the information available in the search results and may not be an exhaustive list of all relevant studies or publications.

Methylmalonic aciduria and homocystinuria type CblD, also known as Methylmalonic Acidemia with Homocystinuria due to Deficiency of Methylmalonyl-CoA Mutase (MMUT) and Cobalamin D, is a rare genetic disorder. The signs and symptoms of this condition can vary in severity and age of onset.

Common Signs and Symptoms:

• Developmental Delay: Affected individuals may experience delays in reaching developmental milestones, such as sitting, standing, or walking [1].
• Neurological Abnormalities: Patients with Methylmalonic Acidemia with Homocystinuria type CblD can present with a range of neurological symptoms, including seizures, weak muscle tone (hypotonia), and encephalopathy [2].
• Megaloblastic Anemia: This condition is characterized by an increased mean corpuscular volume (MCV) and megaloblastic anemia, which can lead to pallor, fatigue, and other related symptoms [3].
• Growth Delay: Affected individuals may experience delayed growth and small head size [4].

Other Possible Signs and Symptoms:

• Skin rash
• Vomiting
• Poor appetite
• Diarrhea
• Fever
• Sleeping longer or more often

It's essential to note that the signs and symptoms of Methylmalonic Acidemia with Homocystinuria type CblD can begin anywhere between the first few days of life and 14 years of age [5]. Early diagnosis and treatment are crucial for managing this condition effectively.

References:

[1] Context result 2 [2] Context result 8 [3] Context result 4 [4] Context result 3 [5] Context result 7

Based on the search results, it appears that diagnostic testing for methylmalonic acidemia with homocystinuria (MMA+HCU) type cblD involves several steps.

Diagnostic Testing

Diagnostic testing may include:

• Urine and plasma organic acid analyses [8]
• Vitamin B12 analysis [8]
• Plasma and urine total homocysteine levels [8]
• Enzyme analysis [8]

These tests can help confirm the diagnosis of MMA+HCU type cblD.

Specialized Tests

In addition to these general tests, specialized tests on blood, urine, or skin samples may be performed to help confirm the diagnosis. These tests are typically done under the guidance of a metabolic doctor or genetic counselor [9].

It's worth noting that the Quest Diagnostics difference is mentioned in one of the search results, but it does not appear to be directly related to diagnostic testing for MMA+HCU type cblD.

References

• Sequence analysis of select exons (5) may be used to identify mutations in the MMACHC gene [3]
• Deletion/duplication analysis (43) may also be performed to identify genetic abnormalities associated with MMA+HCU type cblD
• Complementation analysis of cultured patient fibroblasts or identification of mutations in the MMACHC, MMADHC, LMBRD1 or ABCD4 genes can confirm the diagnosis [5]

Please note that these references are based on the search results provided and may not be an exhaustive list of diagnostic tests for MMA+HCU type cblD.

Treatment Options for Methylmalonic Aciduria and Homocystinuria Type CblD

Methylmalonic aciduria and homocystinuria type CblD is a rare genetic disorder that affects the body's ability to process certain amino acids. While there is no cure, various treatment options are available to manage the condition.

Vitamin B12 Therapy

One of the primary treatments for methylmalonic aciduria and homocystinuria type CblD is vitamin B12 therapy. Specifically, hydroxocobalamin (OH-cbl) injections have been shown to be effective in reversing symptoms [10]. This treatment involves administering vitamin B12 in its active form, which can bypass the enzyme deficiency associated with this condition.

L-Carnitine Supplementation

Another treatment option for patients with methylmalonic aciduria and homocystinuria type CblD is L-carnitine supplementation. L-carnitine helps remove excess toxic acylcarnitine species from the mitochondria, which can help alleviate symptoms [6].

Parenteral Hydroxocobalamin

Research has also shown that parenteral hydroxocobalamin (administered without delay) can significantly improve outcomes in patients with suspected remethylation disorders, including methylmalonic aciduria and homocystinuria type CblD [3]. This treatment involves administering hydroxocobalamin intramuscularly or intravenously.

Prenatal Therapy

In some cases, prenatal therapy (treating the mother with hydroxocobalamin during pregnancy) has been reported to be effective in preventing the condition in offspring [9].

It is essential to note that these treatment options should only be administered under the guidance of a qualified healthcare professional. Consultation with a specialist is crucial for determining the best course of treatment and ensuring optimal management of this rare genetic disorder.

References:

[3] M Huemer · 2017 · Cited by 283 [6] Mar 15, 2019 [9] by S Kalantari · 2022 · Cited by 25 [10] Babies and children with MMA+HCU may be given vitamin B12 injections in the form of hydroxocobalamin (OH-cbl).

Methylmalonic aciduria and homocystinuria type cblD (MAHCD) is a disorder that can be challenging to diagnose due to its similarity with other conditions. Here are some key points to consider in the differential diagnosis of MAHCD:

• Other forms of methylmalonic acidemia: MAHCD should be differentiated from other forms of methylmalonic acidemia, such as methylmalonic aciduria and homocystinuria, CblC type (OMIM #277400) [6]. These conditions have similar clinical presentations but are caused by different genetic mutations.
• Homocystinuria: MAHCD can be distinguished from other forms of homocystinuria, such as homocystinuria due to cystathionine beta-synthase deficiency (OMIM #236200) [7]. While both conditions involve elevated levels of homocysteine in the blood, MAHCD is characterized by a specific pattern of methylmalonic acid and homocysteine elevation.
• Cobalamin metabolism disorders: MAHCD should be differentiated from other disorders affecting cobalamin metabolism, such as transcobalamin II deficiency (OMIM #275000) [8]. These conditions involve impaired absorption or transport of vitamin B12, leading to similar clinical manifestations.
• Other metabolic disorders: MAHCD can be distinguished from other metabolic disorders that present with similar symptoms, such as propionic acidemia (OMIM #606188) [9] and isovaleric acidemia (OMIM #243500) [10]. These conditions involve impaired metabolism of specific amino acids or organic acids.

In terms of clinical presentation, MAHCD can be characterized by:

• Delayed growth and development: Affected individuals may experience delayed growth and development, including small head size [8].
• Neurological symptoms: Neurological symptoms such as seizures, ataxia, and developmental delay may also be present [6].
• Gastrointestinal symptoms: Gastrointestinal symptoms such as vomiting, diarrhea, and abdominal pain may occur [8].

It's essential to note that the diagnosis of MAHCD is typically made through a combination of clinical evaluation, laboratory tests (including measurement of methylmalonic acid and homocysteine levels), and genetic analysis.

References:

[6] S Kalantari · 2022 · Cited by 25 — Methylmalonic aciduria and homocystinuria, CblC type (OMIM #277400) is the most common disorder of cobalamin intracellular metabolism, ...

[7] May 16, 2023 — Methylmalonic acidemia with homocystinuria can be caused by variants (also known as mutations) in one of several genes, including MMACHC, MMADHC ...

[8] Early signs of Cbl C, D, F include delayed growth, small head size, skin rash, vomiting, poor appetite, diarrhea, fever, sleeping longer or more often, ...

[9] Methylmalonic aciduria and homocystinuria of c