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Deficiency of iodide peroxidase(TDH2A)

MedGen UID:
226940
Concept ID:
C1291299
Disease or Syndrome
Synonyms: Congenital Hypothyroidism, TPO-Related; HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 2A; IODIDE PEROXIDASE DEFICIENCY; TDH2A; Thyroid dyshormonogenesis 2A; THYROID HORMONOGENESIS, GENETIC DEFECT IN, 2A; THYROID PEROXIDASE DEFICIENCY
SNOMED CT: Deficiency of iodinase (124204003); Deficiency of iodide peroxidase (124204003)
 
Gene (location): TPO (2p25.3)
 
Monarch Initiative: MONDO:0010133
OMIM®: 274500

Definition

Approximately 10% of patients with congenital hypothyroidism harbor inborn errors of metabolism in one of the steps for thyroid hormone synthesis in thyrocytes (Vono-Toniolo et al., 2005). The most prevalent cause of thyroid dyshormonogenesis is TPO deficiency (Park and Chatterjee, 2005). Defects in TPO cause a severe form of congenital hypothyroidism characterized by a complete and immediate release of accumulated radioiodide from the thyroid after sodium perchlorate administration (Bakker et al., 2000). This release of radioiodide represents total iodine organification defect (TIOD), a disruption of the process by which iodide present in the thyroid is oxidized by hydrogen peroxide and bound to tyrosine residues in thyroglobulin (TG; 188450) to form iodotyrosine. [from OMIM]

Additional description

From MedlinePlus Genetics
Congenital hypothyroidism is a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital). The thyroid gland is a butterfly-shaped tissue in the lower neck. It makes iodine-containing hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). People with congenital hypothyroidism have lower-than-normal levels of these important hormones.

Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. In 80 to 85 percent of cases, the thyroid gland is absent, severely reduced in size (hypoplastic), or abnormally located. These cases are classified as thyroid dysgenesis. In the remainder of cases, a normal-sized or enlarged thyroid gland (goiter) is present, but production of thyroid hormones is decreased or absent. Most of these cases occur when one of several steps in the hormone synthesis process is impaired; these cases are classified as thyroid dyshormonogenesis. Less commonly, reduction or absence of thyroid hormone production is caused by impaired stimulation of the production process (which is normally done by a structure at the base of the brain called the pituitary gland), even though the process itself is unimpaired. These cases are classified as central (or pituitary) hypothyroidism.

Signs and symptoms of congenital hypothyroidism result from the shortage of thyroid hormones. Affected babies may show no features of the condition, although some babies with congenital hypothyroidism are less active and sleep more than normal. They may have difficulty feeding and experience constipation. If untreated, congenital hypothyroidism can lead to intellectual disability and slow growth. In the United States and many other countries, all hospitals test newborns for congenital hypothyroidism. If treatment begins in the first two weeks after birth, infants usually develop normally.

Congenital hypothyroidism can also occur as part of syndromes that affect other organs and tissues in the body. These forms of the condition are described as syndromic. Some common forms of syndromic hypothyroidism include Pendred syndrome, Bamforth-Lazarus syndrome, and brain-lung-thyroid syndrome.  https://medlineplus.gov/genetics/condition/congenital-hypothyroidism

Clinical features

From HPO
Goiter
MedGen UID:
42270
Concept ID:
C0018021
Disease or Syndrome
An enlargement of the thyroid gland.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Thyroid defect in oxidation and organification of iodide
MedGen UID:
336419
Concept ID:
C1848800
Finding
Decreased circulating T4 concentration
MedGen UID:
1611997
Concept ID:
C4531078
Finding
A reduction below the normal concentration of thyroxine in the blood. Thyroxine (also known as T4) is the main hormone secreted by the thyroid gland into the blood. It can be converted into the active form triiodothyronine (also known as T3).

Professional guidelines

PubMed

Krude H, Kühnen P, Biebermann H
Best Pract Res Clin Endocrinol Metab 2015 Jun;29(3):399-413. Epub 2015 Apr 26 doi: 10.1016/j.beem.2015.04.004. PMID: 26051299
Duntas LH, Papanastasiou L, Mantzou E, Koutras DA
Exp Clin Endocrinol Diabetes 1999;107(6):356-60. doi: 10.1055/s-0029-1212126. PMID: 10543412

Recent clinical studies

Etiology

Wu J, Li J, Yan Z, Yu X, Huang H
Osteoporos Int 2024 Jul;35(7):1213-1221. Epub 2024 Apr 12 doi: 10.1007/s00198-024-07083-8. PMID: 38607417
Meng LH, Chen CH, Liu Y, Liang XH, Zhou J, Xian J, Li L, Zhang J, Huang ZX, Qin YF
J Trace Elem Med Biol 2022 Mar;70:126918. Epub 2021 Dec 22 doi: 10.1016/j.jtemb.2021.126918. PMID: 34954562
Rayman MP
Proc Nutr Soc 2019 Feb;78(1):34-44. Epub 2018 Sep 13 doi: 10.1017/S0029665118001192. PMID: 30208979
Wiersinga WM
Clin Endocrinol (Oxf) 2013 Aug;79(2):145-51. Epub 2013 May 11 doi: 10.1111/cen.12222. PMID: 23581474
Pearce EN, Braverman LE
Best Pract Res Clin Endocrinol Metab 2009 Dec;23(6):801-13. doi: 10.1016/j.beem.2009.06.003. PMID: 19942155

Diagnosis

Refetoff S, Dumitrescu AM
Best Pract Res Clin Endocrinol Metab 2007 Jun;21(2):277-305. doi: 10.1016/j.beem.2007.03.005. PMID: 17574009
Kumar PG, Anand SS, Sood V, Kotwal N
Indian Pediatr 2005 Dec;42(12):1233-5. PMID: 16424561
Glaser B
Pediatr Endocrinol Rev 2003 Dec;1 Suppl 2:199-204; discussion 204. PMID: 16444159
Grüters A, Biebermann H, Krude H
Horm Res 2003;59 Suppl 1:24-9. doi: 10.1159/000067841. PMID: 12566717
Delahunty C, Simpson J, Richard K, Coughtrie M, Williams F, Murphy N, Matthews T, Visser T, Hume R
Dev Med Child Neurol Suppl 2001 Mar;86:26-7. doi: 10.1111/j.1469-8749.2001.tb04144.x. PMID: 11268721

Therapy

Rayman MP
Proc Nutr Soc 2019 Feb;78(1):34-44. Epub 2018 Sep 13 doi: 10.1017/S0029665118001192. PMID: 30208979
Wiersinga WM
Clin Endocrinol (Oxf) 2013 Aug;79(2):145-51. Epub 2013 May 11 doi: 10.1111/cen.12222. PMID: 23581474
Köhrle J, Gärtner R
Best Pract Res Clin Endocrinol Metab 2009 Dec;23(6):815-27. doi: 10.1016/j.beem.2009.08.002. PMID: 19942156
Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J
Nature 2006 Jan 26;439(7075):484-9. Epub 2006 Jan 8 doi: 10.1038/nature04330. PMID: 16400329
Wijeyaratne CN, Jayasinghe A, de Silva DG, Parkes AB, Lazarus JH, Premawardhana LD
Ceylon Med J 2005 Mar;50(1):20-3. doi: 10.4038/cmj.v50i1.1585. PMID: 15881560

Prognosis

Wu Q, Wang Y, Chen P, Wei J, Lv H, Wang S, Wu Y, Zhao X, Peng X, Rijntjes E, Wang Y, Schomburg L, Shi B
J Clin Endocrinol Metab 2022 Aug 18;107(9):e3603-e3611. doi: 10.1210/clinem/dgac410. PMID: 35789269
Belay A, Joy EJM, Chagumaira C, Zerfu D, Ander EL, Young SD, Bailey EH, Lark RM, Broadley MR, Gashu D
Nutrients 2020 May 27;12(6) doi: 10.3390/nu12061565. PMID: 32471236Free PMC Article
Bruellman RJ, Watanabe Y, Ebrhim RS, Creech MK, Abdullah MA, Dumitrescu AM, Refetoff S, Weiss RE
J Clin Endocrinol Metab 2020 May 1;105(5):1564-72. doi: 10.1210/clinem/dgz297. PMID: 31867598Free PMC Article
Gärtner R
J Trace Elem Med Biol 2009;23(2):71-4. Epub 2009 Feb 25 doi: 10.1016/j.jtemb.2009.01.001. PMID: 19398053
Meller J, Becker W
Eur J Nucl Med Mol Imaging 2002 Aug;29 Suppl 2:S425-38. Epub 2002 May 15 doi: 10.1007/s00259-002-0811-8. PMID: 12192542

Clinical prediction guides

Carcelén JN, Marchante-Gayón JM, Rodríguez-González P, Ballesteros A, González JM, Cocho de Juan JÁ, García Alonso JI
Analyst 2022 Mar 28;147(7):1329-1340. doi: 10.1039/d1an02203b. PMID: 35262098
Rayman MP
Proc Nutr Soc 2019 Feb;78(1):34-44. Epub 2018 Sep 13 doi: 10.1017/S0029665118001192. PMID: 30208979
Wiersinga WM
Clin Endocrinol (Oxf) 2013 Aug;79(2):145-51. Epub 2013 May 11 doi: 10.1111/cen.12222. PMID: 23581474
Duntas LH
J Clin Endocrinol Metab 2010 Dec;95(12):5180-8. Epub 2010 Sep 1 doi: 10.1210/jc.2010-0191. PMID: 20810577
Corvilain B, Contempré B, Longombé AO, Goyens P, Gervy-Decoster C, Lamy F, Vanderpas JB, Dumont JE
Am J Clin Nutr 1993 Feb;57(2 Suppl):244S-248S. doi: 10.1093/ajcn/57.2.244S. PMID: 8427197

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