Transthyretin

Serum transport protein that is produced in humans mainly in the choroidal plexus and liver. Transthyretin is responsible for the transport of thyroid hormones (thyroxine) and retinol-binding protein.

In its physiological form, transthyretin has a so-called β leaflet structure. The presence of this structure is a prerequisite for the formation of amyloid deposits. Both the physiologically present protein form and mutations can cause amyloidosis.

Mutations in the TTR gene (> 80 so-called amyloidogenic mutations in the transthyretin gene are known) can cause a lack of physiological transthyretin. Pathological transthyretin can cause transthyretin-type amyloidosis (see below hereditary systemic amyloidosis, skin symptoms are rare as in all systemic amyloidoses) as well as hyperthyroxinemia.

Under certain circumstances, the physiologically present transthyretin is also able to deposit amyloid, e.g. in the connective tissue of the heart. Such a condition leads to non-hereditary systemic amyloidosis.

In serum electrophoresis, transthyretin migrates before the albumin fraction (prealbumin). It is involved in the binding of thyroxine and retinol and has a molar mass of about 55 kDa.

Transthyretin is reduced in chronic active inflammatory states. Transthyretin is therefore also called anti-acute phase protein (see below C-reactive protein).

1. Ferreira AC et al (2012) Familial amyloidotic polineuropathy and systemic lupus. Lupus 21:1455-1458
2. Hagenacker T et al (2014) First report of a rare mutation in a Polish patient with painful late-onset transthyretin amyloidosis. J Neurol Sci 346:331-332
3. Harkany Tet al (2002) Cutaneous lymphatic amyloid deposits in Hungarian-type familial transthyretin amyloidosis: a case report. Br J Dermatol 146:674-679
4. Magy N et al (2003) A transthyretin mutation (Tyr78Phe) associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis. Amyloid 10:29-33
5. White JT et al (2001) Support for the multigenic hypothesis of amyloidosis: The binding stoichiometry of retinol-binding protein, vitamin A, and thyroid hormone influencestransthyretin amyloidogenicity in vitro. Proc Natl Acad Sci 98: 13019-13024