Thyroid dyshormonogenesis is mainly caused by <i><scp>TPO</scp></i> mutations in consanguineous community

Cangül, Hakan; Aycan, Zehra; Olivera-Nappa, Álvaro; Sağlam, Hilal; Schoenmakers, Nadia; Boelaert, Kristien; Çeti̇nkaya, Semra; Tarım, Ömer; Böber, Ece; Darendelıler, Feyza; Baş, Veysel Nijat; Demir, Korcan; Aydın, Banu Küçükemre; Kendall, Michaela; Cole, Trevor; Högler, Wolfgang; Chatterjee, Krishna; Barrett, Timothy; Maher, Eamonn R.

doi:10.1111/cen.12127

Cited by 48 publications

(33 citation statements)

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“…Given that iodine intake may alter the phenotype of TPO and DUOX2 mutations causing iodine organification defects (8,43,44,45), it is even possible that iodine deficiency in our region might have increased the expressivity of gene defects. In Turkey, permanent CH due to dyshormonogenesis is mainly caused by TPO mutations (46), but there is no study investigating the genetic background in transient CH.…”

Section: Discussionmentioning

confidence: 99%

Transient Congenital Hypothyroidism in Turkey: An Analysis on Frequency and Natural Course

Kara

Gunindi²,

Yılmaz³

et al. 2016

Jcrpe

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Objective: Prevalence of congenital hypothyroidism (CH) in Turkey at birth was reported to be as high as 1:650 in 2008-2010. Incidence rates of permanent and transient CH separately are unknown due to lack of follow-up data. We aimed to evaluate the impact of transient hypothyroidism on increasing incidence of CH and to determine the natural course and the clinical, biochemical, and imaging characteristics of transient CH.Methods: Baseline and follow-up data of the infants with CH detected at screening in six provinces in the Black Sea Region were analyzed retrospectively during a time period covering the years 2008-2010.Results: Among 138 cases (48% female), 16 (12%) showed transient hyperthyrotropinemia which resolved without intervention. Of the treated 122 cases, 63 (52%) had transient CH. While its frequency was 35% in 2008, it increased to 56% in 2009-2010, following a lowering of the thyroid stimulating hormone cutoff value. The frequency was higher in inland provinces than in coast (67% vs. 43%; p=0.01).Clinical characteristics of permanent and transient cases were similar except female-to-male sex ratios (1.5:1 vs. 0.6:1; p=0.02). L-thyroxine was discontinued in 70% of transient cases before 3 years of age at a median age of 19 (2-36) months. The only indication for early discontinuation of treatment was a low L-thyroxine dose, which was 1.25±0.27 µg/kg/day at withdrawal time.Conclusion: Our regional follow-up data showed that more than half of newborns with primary CH had transient thyroid dysfunction. In the majority of cases, discrimination between transient and permanent CH can be made before age 3 years, as indicated by cessation of L-thyroxine treatment.

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Section: Discussionmentioning

confidence: 99%

Transient Congenital Hypothyroidism in Turkey: An Analysis on Frequency and Natural Course

Kara

Gunindi²,

Yılmaz³

et al. 2016

Jcrpe

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“…The defects are autosomal recessive and include mutations in genes encoding the sodium-iodide symporter (NIS) (SLC5A5 gene), thyroperoxidase (TPO), hydrogen peroxide generation factors [thyroid oxidase and dual oxidase maturation factors (DUOXA1 and DUOX2 genes)], thyroglobulin (Tg) and iodothyronine deiodinases (13).…”

Section: What Are the Causes Of Ch?mentioning

confidence: 99%

Hipotireoidismo congênito: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

Maciel

Kimura²,

Nogueira

et al. 2013

Arq Bras Endocrinol Metab

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Congenital hypothyroidism (CH) is the most common congenital endocrine disorder, with an incidence of 1:2,000 to 1:4,000 live births and it is a leading preventable mental retardation. Neonatal Screening Programs allow early identification of the disease and the adequate treatment of affected children can avoid the complications related to deprivation of the hormone. Most cases of primary congenital hypothyroidism (85%) are due to thyroid dysgenesis (ectopia, hypoplasia or agenesis) while the remaining result from defects in hormone synthesis. Affected children (> 95%) usually have no symptoms suggesting the disease at birth. The most frequent symptoms and signs are prolonged neonatal jaundice, hoarse cry, lethargy, slow movements, constipation, macroglossia, umbilical hernia, large fontanelle, hypotonia and dry skin. Around the world, various strategies are used for the screening of the CH. In Brazil, screening for CH is mandatory by law and usually done by serum TSH in dried blood collected from the heel. The recommended age for performing this test is after 48 hours of life until the 4 th day. Diagnostic confirmation is required dosing TSH and free T 4 or total T 4 in serum. Arq Bras Endocrinol Metab. 2013;57(3):184-92Keywords Congenital hypothyroidism; neonatal screening RESUMO O hipotireoidismo congênito (HC) é o distúrbio endócrino congênito mais frequente, com incidência variando de 1:2.000 a 1:4.000 crianças nascidas vivas e uma das principais causas de retardo mental que pode ser prevenida. Os Programas de Triagem Neonatal para a doença permitem a identificação precoce dos afetados e seu tratamento de modo a evitar as complicações da falta do hormônio. A maioria dos casos de hipotireoidismo congênito é decorrente de disgenesias tireoidianas (85%), entre elas a ectopia, hipoplasia ou agenesia tireoidianas, e os demais resultam de defeitos de síntese hormonal. As crianças afetadas (> 95%) geralmente não apresentam sintomas sugestivos da doença ao nascimento. Os sintomas e sinais mais comuns são: icterícia neonatal prolongada, choro rouco, letargia, movimentos lentos, constipação, macroglossia, hérnia umbilical, fontanelas amplas, hipotonia e pele seca. Várias estratégias são utilizadas para a triagem do HC. No Brasil, esta é obrigatória por lei e geralmente é feita com a dosagem de TSH em sangue seco coletado do calcanhar. A idade recomendada para sua realização é após as 48 horas de vida até o quarto dia. A confirmação diagnóstica é obrigatória com as dosagens de TSH e T 4 livre ou T 4 total. Arq Bras Endocrinol Metab. 2013;57(3):184-92 Descritores Hipotireoidismo congênito; triagem neonatal

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“…2 Classically, thyroid dyshormonogenesis leads to goiter, although exceptional cases with thyroid atrophy have been described, blurring the distinction between dyshormonogenesis and dysgenesis. 3,4 Although pseudodominant inheritance has been reported, 5 thyroperoxidase deficiency, the commonest form of dyshormonogenesis in most populations, 6 is typically inherited in an autosomal recessive fashion and is accordingly more common in populations with a high degree of consanguinity. 3 In contrast to dyshormonogenesis, the mechanisms underlying CH due to thyroid dysgenesis remain largely unknown, and the proportion of patients in whom a genetic cause has been identified remains extremely small.…”

Section: Introductionmentioning

confidence: 99%

“…3,4 Although pseudodominant inheritance has been reported, 5 thyroperoxidase deficiency, the commonest form of dyshormonogenesis in most populations, 6 is typically inherited in an autosomal recessive fashion and is accordingly more common in populations with a high degree of consanguinity. 3 In contrast to dyshormonogenesis, the mechanisms underlying CH due to thyroid dysgenesis remain largely unknown, and the proportion of patients in whom a genetic cause has been identified remains extremely small. Indeed, this condition was traditionally considered as sporadic until a systematic survey in France revealed that 2% of patients identified by neonatal screening had an affected relative.…”

Section: Introductionmentioning

confidence: 99%

Developmental Abnormalities of the Thyroid

Pohlenz

Vliet

Deladoëy

2016

Genetic Diagnosis of Endocrine Disorders

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Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community

Abstract: This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases.

Cited by 48 publications

References 14 publications

Transient Congenital Hypothyroidism in Turkey: An Analysis on Frequency and Natural Course

Transient Congenital Hypothyroidism in Turkey: An Analysis on Frequency and Natural Course

Hipotireoidismo congênito: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

Developmental Abnormalities of the Thyroid

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