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URL of this page: https://medlineplus.gov/genetics/condition/inherited-thyroxine-binding-globulin-deficiency/

Inherited thyroxine-binding globulin deficiency

Description

Inherited thyroxine-binding globulin deficiency is a genetic condition that typically does not cause health problems.

Thyroxine-binding globulin is one of three major proteins in the bloodstream that carries hormones made by the thyroid gland, a butterfly-shaped tissue in the lower neck. Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Thyroxine is the primary hormone produced by the thyroid gland. In the bloodstream, thyroxine and other thyroid hormones are typically attached (bound) to thyroxine-binding globulin and similar proteins. A shortage (deficiency) of thyroxine-binding globulin reduces the total amount of thyroxine in the blood.

Researchers have identified two forms of inherited thyroxine-binding globulin deficiency: the partial form and the complete form. The partial form reduces the amount of functioning thyroxine-binding globulin. The complete form causes a more significant loss of functioning thyroxine-binding globulin. These conditions typically do not cause problems with thyroid function and are usually identified when bloodwork is performed to rule out other conditions.

Although inherited thyroxine-binding globulin deficiency typically does not cause health problems, it can be mistaken for more serious thyroid disorders, such as hypothyroidism. Therefore, it is important to correctly diagnose the condition to avoid unnecessary treatments.

Frequency

The partial form of inherited thyroxine-binding globulin deficiency, which is the most common form, occurs in approximately 1 in 4,000 infants.

Causes

Variants (also called mutations) in the SERPINA7 gene cause inherited thyroxine-binding globulin deficiency. This gene provides instructions for making thyroxine-binding globulin. Some variants in the SERPINA7 gene lead to a shortened version of thyroxine-binding globulin, which does not function as it should. Other variants change a single protein building block (amino acid) in thyroxine-binding globulin. These variants reduce the amount of functional thyroxine-binding globulin that is available to bind to thyroid hormones.

Some cases of thyroxine-binding globulin deficiency are not inherited but are acquired during a person’s lifetime. Acquired thyroxine-binding globulin deficiency can have several causes, including malnutrition, kidney disease, liver disease, and an increased level of male sex hormones (androgens). Acquired thyroxine-binding globulin deficiency can also occur as a side effect of treatment with certain medications.

Inheritance

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), a variant in the only copy of the gene in each cell is sufficient to cause the condition. In females (who have two copies of the X chromosome), one altered copy of the gene may reduce the amount of thyroxine-binding globulin. However, these individuals often have thyroxine-binding globulin levels that are still within the normal range. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Other Names for This Condition

  • TBG deficiency
  • TBGQTL
  • Thyroxine-binding globulin quantitative trait locus

Additional Information & Resources

Genetic Testing Information

Patient Support and Advocacy Resources

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Chakravarthy V, Ejaz S. Thyroxine-Binding Globulin Deficiency. 2023 Jul 4. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK544274/ Citation on PubMed
  • Fang Y, Chen H, Chen Q, Wang C, Liang L. Compound hemizygous variants in SERPINA7 gene cause thyroxine-binding globulin deficiency. Mol Genet Genomic Med. 2021 Feb;9(2):e1571. doi: 10.1002/mgg3.1571. Epub 2021 Feb 7. Citation on PubMed
  • Knobel M, Medeiros-Neto G. An outline of inherited disorders of the thyroid hormone generating system. Thyroid. 2003 Aug;13(8):771-801. doi: 10.1089/105072503768499671. Citation on PubMed
  • Mandel S, Hanna C, Boston B, Sesser D, LaFranchi S. Thyroxine-binding globulin deficiency detected by newborn screening. J Pediatr. 1993 Feb;122(2):227-30. doi: 10.1016/s0022-3476(06)80117-4. Citation on PubMed
  • Okamoto H, Mori Y, Tani Y, Nakagomi Y, Sano T, Ohyama K, Saito H, Oiso Y. Molecular analysis of females manifesting thyroxine-binding globulin (TBG) deficiency: selective X-chromosome inactivation responsible for the difference between phenotype and genotype in TBG-deficient females. J Clin Endocrinol Metab. 1996 Jun;81(6):2204-8. doi: 10.1210/jcem.81.6.8964852. Citation on PubMed
  • Pappa T, Ferrara AM, Refetoff S. Inherited defects of thyroxine-binding proteins. Best Pract Res Clin Endocrinol Metab. 2015 Oct;29(5):735-47. doi: 10.1016/j.beem.2015.09.002. Epub 2015 Sep 30. Citation on PubMed
  • Schussler GC. The thyroxine-binding proteins. Thyroid. 2000 Feb;10(2):141-9. doi: 10.1089/thy.2000.10.141. Erratum In: Thyroid 2000 Apr;10(4):372. Citation on PubMed

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