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Thyroglobulin synthesis defect(TDH5)

MedGen UID:
87430
Concept ID:
C0342196
Disease or Syndrome
Synonyms: HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 5; TDH5; Thyroid dyshormonogenesis 5; THYROID HORMONOGENESIS, GENETIC DEFECT IN, 5
SNOMED CT: Thyroglobulin synthesis defect (63127008); Hypothyroidism due to thyroglobulin biosynthetic defect (63127008); Genetic defect in thyroid hormonogenesis V (63127008); Hypothyroidism due to thyroglobulin synthesis defect (63127008)
 
Gene (location): DUOXA2 (15q21.1)
 
Monarch Initiative: MONDO:0010137
OMIM®: 274900

Definition

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.

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 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. [from MedlinePlus Genetics]

Clinical features

From HPO
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
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.

Professional guidelines

PubMed

Fugazzola L, Muzza M, Weber G, Beck-Peccoz P, Persani L
Ann Endocrinol (Paris) 2011 Apr;72(2):82-6. Epub 2011 Apr 20 doi: 10.1016/j.ando.2011.03.004. PMID: 21511237
Schlumberger M, Lacroix L, Russo D, Filetti S, Bidart JM
Nat Clin Pract Endocrinol Metab 2007 Mar;3(3):260-9. doi: 10.1038/ncpendmet0449. PMID: 17315034
LaFranchi S
Thyroid 1999 Jul;9(7):735-40. doi: 10.1089/thy.1999.9.735. PMID: 10447022

Recent clinical studies

Etiology

Kızılcan Çetin S, Aycan Z, Şıklar Z, Dizbay Sak S, Ceylaner S, Özsu E, Berberoğlu M
J Clin Res Pediatr Endocrinol 2024 Sep 5;16(3):340-343. Epub 2022 Dec 1 doi: 10.4274/jcrpe.galenos.2022.2022-8-20. PMID: 36453602Free PMC Article

Diagnosis

Kızılcan Çetin S, Aycan Z, Şıklar Z, Dizbay Sak S, Ceylaner S, Özsu E, Berberoğlu M
J Clin Res Pediatr Endocrinol 2024 Sep 5;16(3):340-343. Epub 2022 Dec 1 doi: 10.4274/jcrpe.galenos.2022.2022-8-20. PMID: 36453602Free PMC Article
Dias VM, Campos AP, Chagas AJ, Silva RM
J Pediatr Endocrinol Metab 2010 Aug;23(8):815-26. doi: 10.1515/jpem.2010.131. PMID: 21073124
van de Graaf SA, Cammenga M, Ponne NJ, Veenboer GJ, Gons MH, Orgiazzi J, de Vijlder JJ, Ris-Stalpers C
Biochimie 1999 May;81(5):425-32. doi: 10.1016/s0300-9084(99)80091-1. PMID: 10403171

Prognosis

Dias VM, Campos AP, Chagas AJ, Silva RM
J Pediatr Endocrinol Metab 2010 Aug;23(8):815-26. doi: 10.1515/jpem.2010.131. PMID: 21073124

Clinical prediction guides

Kızılcan Çetin S, Aycan Z, Şıklar Z, Dizbay Sak S, Ceylaner S, Özsu E, Berberoğlu M
J Clin Res Pediatr Endocrinol 2024 Sep 5;16(3):340-343. Epub 2022 Dec 1 doi: 10.4274/jcrpe.galenos.2022.2022-8-20. PMID: 36453602Free PMC Article

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