Hipervitaminosis B12: Nuestra experiencia y una revisión / Hypervitaminosis B12. Our experience and a review

Los altos niveles de vitamina B12 o cobalamina, también denominado hipervitaminosis B12 es una anormalidad analítica frecuentemente subestimada. De acuerdo con la literatura algunas de las entidades relacionadas con este hallazgo son las neoplasias sólidas (primarias o metastásicas) y las enfermedades hematológicas agudas o crónicas. Otras causas incluyen la afección hepática, la gammapatía monoclonal de significación indeterminada, la insuficiencia renal y, con menor frecuencia, un exceso de consumo de vitamina B12, enfermedades inflamatorias o autoinmunes y los trastornos hematológicos transitorios (neutrofilia y eosinofilia secundaria). Este artículo informa sobre causas de hipervitaminosis B12, nuestra experiencia y hace una revisión de la literatura.

High serum levels of vitamin B12 or cobalamin, also called hypervitaminemia B12, is a frequently underestimated biological abnormality. According to the literature, some of the entities related to this finding are solid neoplasia (primary or metastatic) and acute or chronic hematological diseases. Other causes include liver disorders, monoclonal gammapathy of undetermined significance, renal failure and, less frequently, excess of vitamin B12 intake, inflammatory or autoimmune diseases, and transient hematological disorders (neutrophilia and secondary eosinophilia). This article reports on causes of hypervitaminosis B12, our experience and a review of the literature.

Hampered Vitamin B12 Metabolism in Gaucher Disease?

Abstract Untreated vitamin B12 deficiency manifests clinically with hematological abnormalities and combined degeneration of the spinal cord and polyneuropathy and biochemically with elevated homocysteine (Hcy) and methylmalonic acid (MMA). Vitamin B12 metabolism involves various cellular compartments including the lysosome, and a disruption in the lysosomal and endocytic pathways induces functional deficiency of this micronutrient. Gaucher disease (GD) is characterized by dysfunctional lysosomal metabolism brought about by mutations in the enzyme beta-glucocerebrosidase (Online Mendelian Inheritance in Man (OMIM): 606463; Enzyme Commission (EC) 3.2.1.45, gene: GBA1). In this study, we collected and examined available literature on the associations between GD, the second most prevalent lysosomal storage disorder in humans, and hampered vitamin B12 metabolism. Results from independent cohorts of patients show elevated circulating holotranscobalamin without changes in vitamin B12 levels in serum. Gaucher disease patients under enzyme replacement therapy present normal levels of Hcy and MMA. Although within the normal range, a significant increase in Hcy and MMA with normal serum vitamin B12 was documented in treated GD patients with polyneuropathy versus treated GD patients without polyneuropathy. Thus, a functional deficiency of vitamin B12 caused by disrupted lysosomal metabolism in GD is a plausible mechanism, contributing to the neurological form of the disorder but this awaits confirmation. Observational studies suggest that an assessment of vitamin B12 status prior to the initiation of enzyme replacement therapy may shed light on the role of vitamin B12 in the pathogenesis and progression of GD.

Hypercobalaminemia Induced by an Energy Drink after Total Gastrectomy: A Case Report / Journal of Rural Medicine

We encountered a case of hypercobalaminemia induced by oral intake of an energy drink after total gastrectomy. The patient was referred to our hospital due to findings suspicious for gastric cancer on screening. A 20 mm type 0-IIc lesion was detected in the gastric subcardia on esophagogastroduodenoscopy. Total gastrectomy followed by Roux-en-Y reconstruction was performed. He was discharged without complications. His basal serum vitamin B₁₂ level was initially maintained with monthly intramuscular injections of vitamin B₁₂. After 9 months, his serum vitamin B₁₂ level suddenly increased up to 36-fold higher than the normal range and persisted there for one year without vitamin B₁₂ injections. The patient ultimately reported consuming half a bottle of an energy drink each day during this time period. This case demonstrates the risk of unexpected hypervitaminemia resulting from self-administration of nutritional supplements.

Serum transcobalamin II level in a malarial patient with ceftriaxone-induced haemolyic anaemia.

Cephalosporins have rarely been reported as the cause of immune haemolytic anaemia (IHA). The case history of a patient who had elevated serum transcobalamin II (TCII) levels due to a ceftriaxone-induced haemloytic anaemia is presented in this study. The patient was admitted because of high fever due to P.falciparum. The fever subsided after treatment with anti-malarial drugs. However, two days later, the fever recurred and ceftriazone was given. On the next day, the patient had haemolysis with haemoglobinuria and renal insufficiency which resolved after withdrawal of the drug. Serum TCII levels were elevated during the haemolytic episode and the period of renal impairment. The mechanisms of increased serum TCII are probably due to the acute haemolysis and nephrotoxicityinduced by ceftriaxone, leading to the impaired catabolism and clearance of TCII. Therefore, intravascular THII survival is prolonged. Resulting in elevated serum TCIIlevels.

Persistently elevated serum transcobalamin II in a patient with reactive haemophagocytic syndrome.

A 24-year-old man was admitted to the hospital with a history of prolonged fever, peripheral blood neutropenia and bone marrow showing benign haemophagocytic histiocytosis. He presented with symptoms and manifestations over a brief duration until death, with the progressive development of multi-organ dysfunction. His serum TCII levels were persistently elevated throughout the disease duration in the hospital. Available evidence indicates that macrophages, mononuclear cells and histiocytes can produce TCII. Serum TCII levels in patients with reactive haemophagocytic syndrome are therefore elevated due to the increased be helpful in making the diagnosis in these patients.

Increased circulating levels of transcobalamin II in typhoid fever.

Many previous studies have shown that serum transcobalamin II (TCII) is usually elevated in patients with a stimulated and proliferative reticuloendothelial system resulting from such diseases as multiple myeloma, systemic lupus erythrematosus, dermatomyositis, rheumatoid arthritis and Gaucher’s disease. As reactive macrophage hyperplasia with monocytosis also occurs in patients with typhoid fever, we therefore studied TCII in these patients. The mean value of serum TCII was significantly higher in the typhoid patients’ group, and 15 out of 35 patients had serum TCII values over 2,000 pg/ml. There was no relationship between serum TCII and white blood count, haemoglobin or haematocrit values. The increased serum TCII level in typhoid patients was possibly due to increased synthesis by the proliferative mononuclear cells derived from reticuloendothelial tissue in various organs such as the spleen, liver and mesenteric lymph nodes. This supposition is supported by a previous report that TCII is synthesized in part by mouse peritoneal macrophages, as well as by human monocytes and macrophages which produced and secreted considerable amounts of TCII into the medium. Findings of increased serum TCII in typhoid patients therefore add a new area of information which has never been studied before.

Elevated serum transcobalamin II levels in patients with prolonged fever.

Serum transcobalamin II levels were determined in 70 patients with prolonged fever. Twelve patients were found to have elevated serum TCII levels, i.e., 8 patients with salmonellosis, 3 patients with scrub typhus and 1 patient with pyrexia of unknown origin. There were no relationships between serum TCII levels and white blood cells, lymphocytes or monocytes. The possible mechanism producing increased serum TCIII levels in patients with salmonellosis and scrub typhus is the increased synthesis and release of TCII by the proliferative mononuclear phagocytic cells of the reticuloendothlial tissues such as spleen, liver, bone marrow and lymph nodes. This study gives the additional data that elevated serum TCII may occur not only in inflammatory disorders, autoimmune diseases, lymphoproliferative disorders, malignant histiocytosis and neoplasms, but also in infection with salmonellosis and scrub typhus.

Serum transcobalamin II in childhood histiocytosis syndromes.

It has been shown in a previous report that an extreme high serum TCII level was found in patients with malignant histiocytosis and patients with proliferative histiocytosis. The objective of the present study was to Langerhans cells histiocytosis and 6 patients with malignant histiocytosis. Serum TCII levels in both groups of patients were not significantly different from those of normal subjects. Furthermore, serum vitamin B12 and other transcobalamins levels were also within the normal limits. These findings do not support the results reported earlier in adult patients either with malignant histiocytosis or with proliferative histiocytosis. The suggestion that determination of TCII may be a useful indicator of activity and size of the macrophage/histiocyte system is therefore not proved in childhood histiocytosis syndromes.