Related Experiment Video
Updated: Aug 8, 2026
Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
Published on: September 9, 2012
Mild transcobalamin I (haptocorrin) deficiency and low serum cobalamin concentrations
1Department of Medicine, New York Methodist Hospital, 506 Sixth Street, Brooklyn, NY 11215, USA. rac9001@nyp.org
Insights
Mild Transcobalamin I/haptocorrin (TC I/HC) deficiency is a common cause of unexplained low cobalamin and often runs in families. Severe TC I/HC deficiency may also be more frequent than previously thought.
Area of Science:
- Biochemistry
- Clinical Diagnostics
- Genetics
Background:
- Low cobalamin concentrations are prevalent, with unidentified causes in many cases.
- Transcobalamin I/haptocorrin (TC I/HC) deficiency is considered rare but warrants systematic investigation in unexplained low cobalamin.
- Understanding the prevalence and genetic basis of TC I/HC deficiency is crucial for diagnosing cobalamin-related disorders.
Purpose of the Study:
- To investigate the prevalence of Transcobalamin I/haptocorrin (TC I/HC) deficiency in patients with unexplained low serum cobalamin.
- To determine if mild TC I/HC deficiency is associated with low cobalamin levels and if it has a familial pattern.
- To assess the frequency of severe TC I/HC deficiency in patients with low cobalamin.
Main Methods:
- Radioimmunoassay (RIA) was used to measure total TC I/HC levels in patient subgroups with varying cobalamin concentrations.
- Comparative analysis was performed between patient groups and control groups with normal cobalamin levels.
- Family studies and additional biochemical evaluations were conducted for patients identified with low TC I/HC concentrations.
Main Results:
- Mild TC I/HC deficiency was observed in 15% of patients with low cobalamin, including those with unexplained low levels.
- The prevalence of mild TC I/HC deficiency was significantly lower in patients with malabsorptive causes of low cobalamin and in control groups.
- Severe TC I/HC deficiency was identified in 0.6% of patients with low cobalamin, and familial cases of mild deficiency were noted in several families.
Conclusions:
- Mild TC I/HC deficiency is a frequent finding in patients with low serum cobalamin, particularly when the cause is unexplained.
- The biochemical phenotype of mild TC I/HC deficiency is consistent with the heterozygous state of severe TC I/HC deficiency, suggesting a shared genetic basis.
- Both mild and severe forms of TC I/HC deficiency should be considered in the diagnostic workup of patients presenting with unexplained low cobalamin levels.
Background:
Low cobalamin concentrations are common, but their causes are often unknown. Transcobalamin I/haptocorrin (TC I/HC) deficiency, viewed as a rare cause, has not been examined systematically in patients with unexplained low serum cobalamin.
Methods:
Total TC I/HC was measured by RIA in three subgroups of 367, 160, and 38 patients with different categories of low cobalamin concentrations and three comparison subgroups of 112, 281, and 119 individuals with cobalamin concentrations within the reference interval. Additional studies, including family studies, were done in selected patients found to have low TC I/HC concentrations.
Results:
Low TC I/HC concentrations suggestive of mild TC I/HC deficiency occurred in 54 of 367 (15%) patients with low cobalamin identified by clinical laboratories and 24 of 160 (15%) patients whose low cobalamin was unexplained after absorption and metabolic evaluation, but in only 2 of 38 patients with malabsorptive causes of low cobalamin concentrations (5%). The prevalence was only 3% (8 of 281 plasma samples) to 5% (6 of 112 sera) in patients with cobalamin concentrations within the reference interval and 3% (4 of 119) in healthy volunteers. Three patients with low cobalamin (0.6%) had severe TC I/HC deficiency with undetectable TC I/HC. Presumptive heterozygotes for severe TC I/HC deficiency in two families had the findings of mild TC I/HC deficiency; mild deficiency was also found in at least three of seven studied families of patients with mild TC I/HC deficiency.
Conclusions:
Mild TC I/HC deficiency is frequently associated with low cobalamin, is often familial, and its biochemical phenotype appears identical to the heterozygous state of severe TC I/HC deficiency. Severe TC I/HC deficiency also appears to be more common than suspected. Both diagnoses should be considered in all patients with unexplained low serum cobalamin.
Related Concept Videos
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:27Disorders of Erythrocytes
Erythrocyte disorders can be broadly categorized into two main types: anemic and polycythemic conditions.
A low oxygen-carrying capacity of the blood due to the loss, lower production, or destruction of erythrocytes is termed anemia. Hemorrhagic anemia, for example, occurs when bleeding from an external wound or internal ulcer reduces erythrocyte counts.
On the other...
01:24Disorders of Hemostasis
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
01:30Vitamins
01:29Pulmonary Tuberculosis I
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
01:23Hypothyroidism II: Pathophysiology