transcobalamin II deficiency

Transcobalamin II Deficiency: A Rare Autosomal Recessive Disorder

Transcobalamin II (TC) deficiency, also known as Transcobalamin II deficiency or TCN2D, is a rare autosomal recessive disorder that affects the transport of cobalamin (vitamin B12) within the body. This condition is characterized by a failure to thrive, megaloblastic anemia, and pancytopenia in early infancy.

Key Features:

• Failure to thrive
• Megaloblastic anemia
• Pancytopenia
• Recurrent infections due to immunodeficiency
• Methylmalonic aciduria
• Vomiting and diarrhea

Laboratory Studies:

• Low immunoglobulins and/or deficient specific antibody production
• Abnormalities in the cells responsible for generating or maintaining an antibody response

Causes and Prevalence:

• Caused by biallelic mutations in TCN2 gene
• Rare autosomal recessive disorder with a prevalence of less than 1/1000000.

Clinical Manifestations:

• Classical clinical and laboratory signs present in early infancy, including megaloblastic anemia, failure to thrive, and pancytopenia.
• Neurological complications may also occur.

Treatment and Management:

• Patients often improve with antibiotics but get sick again when these are discontinued.
• Specific treatment for TC deficiency is not available, but supportive care and management of symptoms can help alleviate the condition.

References:

[1] Ratschmann R, Minkov M, Kis A, Hung C, Rupar T, Muhl A, Fowler B, Nexo E, Bodamer OA. Transcobalamin (TC) deficiency--potential cause of bone marrow failure in childhood. J Inherit Metab Dis. 2008 Dec;31 Suppl 2:S287-92.

[2] S Ünal. Transcobalamin II deficiency: a rare autosomal recessive disease characterized by decreased cobalamin availability. Cited by 28, 2019.

[3] MedlinePlus Genetics: 42 Transcobalamin deficiency is a disorder that impairs the transport of cobalamin (also known as vitamin B12) within the body.

Common Signs and Symptoms of Transcobalamin II Deficiency

Transcobalamin II (TC) deficiency is a rare genetic disorder that impairs the transport of vitamin B12 within the body. The absence or malfunctioning of TC leads to severe health complications, which can be life-threatening if left untreated.

• Failure to Thrive: Infants and children with TC deficiency often experience failure to gain weight and grow at the expected rate (failure to thrive) [1].
• Megaloblastic Anemia: A type of anemia characterized by large red blood cells that are unable to function properly, leading to fatigue, weakness, and shortness of breath [2][3].
• Pancytopenia: A condition where there is a decrease in the number of red and white blood cells, as well as platelets, which can lead to infections, anemia, and bleeding problems [4].
• Vomiting and Diarrhea: Frequent episodes of vomiting and diarrhea can occur due to the impaired absorption of nutrients and electrolytes [5][6].
• Lethargy: Infants and children with TC deficiency may appear lethargic or tired due to the lack of essential nutrients and energy [7].
• Recurrent Infections: The impaired immune system can lead to recurrent infections, which can be severe and life-threatening if not treated promptly [8][9].
• Hypogammaglobulinemia: A condition where there is a decrease in the production of antibodies, making it difficult for the body to fight off infections [10].

Early Detection and Treatment are Crucial

It's essential to diagnose TC deficiency early on to prevent long-term health complications. Treatment typically involves vitamin B12 supplements, which can help alleviate symptoms and improve overall health.

References:

[1] - August 18, 2020 [2]

Diagnostic Tests for Transcobalamin II Deficiency

Transcobalamin II (TCII) deficiency is a rare genetic disorder that impairs the transport of vitamin B12 within the body. Diagnosing this condition requires a combination of clinical, biochemical, and molecular genetic data.

• Complete Blood Count (CBC): A CBC test measures various components of blood, including red and white blood cells, to identify any abnormalities. In TCII deficiency, a low white cell count is often observed [5].
• Vitamin B12 Blood Test: This test measures the level of vitamin B12 in the blood. A person with TCII deficiency will have low levels of vitamin B12 [5].
• Deletion/Duplication Analysis: This genetic test identifies any deletions or duplications in the TCN2 gene, which can cause TCII deficiency [6].
• Targeted Variant Analysis: This test analyzes specific variants in the TCN2 gene that are associated with TCII deficiency [7].
• Sequence Analysis of Select Exons: This test examines specific exons (coding regions) of the TCN2 gene to identify any mutations that may cause TCII deficiency [1].
• Sequence Analysis of the Entire Coding Region: This comprehensive genetic test analyzes the entire coding region of the TCN2 gene to identify any mutations or variations that may cause TCII deficiency [43].

Additionally, elevated levels of downstream metabolites, such as methylmalonic acid (MMA) and homocysteine (Hcy), are commonly used as adjuvant diagnostics to confirm a suspected diagnosis of cobalamin deficiency [8].

Treatment Options for Transcobalamin II Deficiency

Transcobalamin II (TCII) deficiency is a rare genetic disorder that affects the transport of vitamin B12 within the body. The good news is that it can be effectively treated with vitamin B12 injections.

• Parenteral Vitamin B12 Injections: According to a study published in 2019, treatment with parenteral vitamin B12 is highly effective in improving clinical and biological signs in patients with TCII deficiency [5].
• Weekly Hydroxocobalamin or Cyanocobalamin Injections: A more recent study from 2021 suggests that IM administration of 1 mg of hydroxocobalamin or cyanocobalamin once a week for a lifetime appears to be the most suitable treatment regime, providing long-term benefits [9].

It's essential to establish an early diagnosis and initiate treatment promptly to prevent complications. Regular monitoring and follow-up appointments with a healthcare provider are also crucial to ensure the effectiveness of the treatment plan.

References:

[5] S Ünal · 2019 · Cited by 28 — Treatment with parenteral vitamin B12 is highly effective on clinical and biological signs. [9] by F Martino · 2021 · Cited by 5 — IM administration of 1 mg of hydroxocobalamin or cyanocobalamin once a week for a lifetime appears to be the most suitable treatment regime.

Understanding Transcobalamin II Deficiency

Transcobalamin II (TCII) deficiency is a rare genetic disorder that affects the body's ability to absorb and utilize vitamin B12. This condition can lead to various health complications, including immunological abnormalities, cytopenia, and neurological dysfunction.

Differential Diagnosis

In cases where TCII deficiency is suspected, it is essential to consider this condition in the differential diagnosis of infants with immunological abnormalities as well as cytopenia and neurological dysfunction [1]. Early recognition and initiation of adequate treatment are critical for controlling the disease and improving prognosis [1].

Clinical Presentation

The first signs of TCII deficiency typically include failure to gain weight and grow at the expected rate (failure to thrive), vomiting, diarrhea, and recurrent infections [2][3]. People with this condition often develop a blood disorder called megaloblastic anemia, which results in a shortage of red blood cells [6].

Diagnostic Criteria

The diagnosis is suggested by the presence of megaloblastic anemia, neurologic abnormalities, failure to thrive, diarrhea, vomiting, and recurrent infections [7]. A complete blood count and serum vitamin B12 level are recommended laboratory evaluations for patients with suspected TCII deficiency [14].

Additional Findings

In some cases, vacuolization in the myeloid lineage in bone marrow aspiration may be an additional finding of TCII deficiency [12]. It is essential to consider this condition in the differential diagnosis of immune deficiency and other related disorders.

References:

[1] S Ünal · 2019 · Cited by 29 — Conclusion: Transcobalamin II deficiency should be considered in the differential diagnosis of infants with immunological abnormalities as well as cytopenia and ...

[2] Oct 1, 2014 — The first signs of transcobalamin deficiency are typically a failure to gain weight and grow at the expected rate (failure to thrive), vomiting, ...

[3] The first signs of transcobalamin deficiency are typically a failure to gain weight and grow at the expected rate (failure to thrive), vomiting, diarrhea, and ...

[6] Oct 1, 2014 — People with transcobalamin deficiency often develop a blood disorder called megaloblastic anemia. Megaloblastic anemia results in a shortage of ...

[7] The diagnosis is suggested by the presence of megaloblastic anemia, neurologic abnormalities, FTT, diarrhea, vomiting, and recurrent infections. Step 1: Immune ...

[12] Suggesting the consideration of transcobalamin II deficiency in the differential diagnosis of immune deficiency. Hemophagocytic lymphohistiocytosis was also detected in one patient.

[14] The recommended laboratory evaluation for patients with suspected vitamin B 12 deficiency includes a complete blood count and serum vitamin B 12 level.