What is cobalamin disease?

Cobalamin C disease (cblC), also known as methylmalonic aciduria with homocystinuria, is an inherited disease characterized by hypotonia, lethargy, intellectual and developmental disabilities, seizures, vision problems, and blood-related problems.

What causes methylmalonic acidemia?

Methylmalonic acidemia has an autosomal recessive pattern of inheritance. Methylmalonic acidemia is caused by a defect in the vitamin B12-dependent enzyme methylmalonyl CoA mutase.

What causes Transcobalamin deficiency?

Mutations in the TCN2 gene cause transcobalamin deficiency. The TCN2 gene provides instructions for making a protein called transcobalamin. This protein attaches (binds) to cobalamin and transports the vitamin to cells throughout the body.

How common is methylmalonic acidemia?

This condition may occur in 1 in 25,000 to 48,000 people but the precise incidence is not known. What is methylmalonic acidemia? Methylmalonic acidemia (MMA) refers to a group of inherited disorders in which the body is unable to process certain proteins and fats (lipids) properly.

How is cobalamin absorbed?

After ingestion, the low stomach pH cleaves cobalamin from other dietary protein. The free cobalamin binds to gastric R binder, a glycoprotein in saliva, and the complex travels to the duodenum and jejunum, where pancreatic peptidases digest the complex and release cobalamin.

What is cobalamin metabolism?

Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism.

Can you live with MMA?

Less severe forms of isolated MMA permit patients to grow into adulthood and lead relatively normal lives unaffected by MMA if symptoms are managed properly. Nonetheless, small missteps can still lead to significant acidosis episodes and possible death.

What are the symptoms of MMA?

Symptoms of a decompensation event include poor feeding, vomiting, trouble breathing, and lack of energy (lethargy). These can occur at different ages and can range from mild to severe. Methylmalonic acidemia is caused by changes in several different genes and is inherited in an autosomal recessive fashion.

Can you take vitamin B12 with polycythemia?

Don’t attempt vitamin B12 therapy without close supervision by your healthcare provider. High numbers of red blood cells (polycythemia vera): The treatment of vitamin B12 deficiency can unmask the symptoms of polycythemia vera.

How is Transcobalamin deficiency diagnosed?

Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene.

Is methylmalonic acidemia inherited?

Methylmalonic acidemia is an inherited disorder in which the body is unable to process certain proteins and fats (lipids) properly. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to life-threatening.

Why is methylmalonic acid high in b12?

Normal Absorption of Vitamin B In humans, only two enzymatic reactions are known to be dependent on vitamin B12. In the first reaction, methylmalonic acid is converted to succinyl-CoA using vitamin B12 as a cofactor (Figure 1). Vitamin B12 deficiency, therefore, can lead to increased levels of serum methylmalonic acid.

What is the pathophysiology of cobalamin deficiency?

Cobalamin deficiency is observed with several diseases, including: Inflammatory bowel disease, GI lymphoma, intestinal dysbiosis, exocrine pancreatic insufficiency, short bowel syndrome, pancreatitis, as well as in cases of gastrinoma, as this can affect both gastric and pancreatic secretion of intrinsic factor.

What does it mean if your cobalamin is high?

Elevated levels of serum cobalamin may be a sign of a serious, even life-threatening, disease. Hematologic disorders like chronic myelogeneous leukemia, promyelocytic leukemia, polycythemia vera and also the hypereosinophilic syndrome can result in elevated levels of cobalamin.

What causes methylmalonic acidemia (cobalamin disorders)?

Methylmalonic acidemia (cobalamin disorders) is caused by changes in either the MMAA or MMAB _ gene. The _MMAA and MMAB genes give your body instructions for proteins that are needed to process vitamin B-12, which helps the enzyme methylmalonyl CoA mutase (mut) to work.

What is the role of cobalamin in the human body?

Cobalamin is an essential cofactor for certain enzyme systems, nucleic acid synthesis, amino acid metabolism and hematopoiesis. Intrinsic factor is required for absorption of cobalamin in the ileum.