MCT8 Deficiency in Infancy: Opportunities for Early Diagnosis and Screening.

IF 4 Q1 GENETICS & HEREDITY
Ilja Dubinski, Belana Debor, Sofia Petrova, Katharina A Schiergens, Heike Weigand, Heinrich Schmidt
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Abstract

Background: Monocarboxylate-transporter-8-(MCT8) deficiency, or Allan-Herndon-Dudley syndrome (AHDS), is a rare X-linked disorder caused by pathogenic variants in the SLC16A2 gene, leading to impaired transport of thyroid hormones, primarily T3 and T4, across cell membranes. The resulting central hypothyroidism and peripheral hyperthyroidism cause neurodevelopmental impairment and thyrotoxicosis. Despite the availability of therapy options, e.g., with triiodothyroacetic acid (TRIAC), diagnosis is often delayed, partly due to normal TSH levels or incomplete genetic panels. MCT8 deficiency is not yet included in newborn-screening programs worldwide.

Case description: We present a case of an infant genetically diagnosed with MCT8 deficiency at 5 months of age after presenting with muscular hypotonia, lack of head control, and developmental delay. Thyroid function testing revealed a normal TSH, low free T4, and significantly elevated free T3 and free T3/T4 ratio. Treatment with TRIAC (Emcitate®) was initiated promptly, with close drug monitoring. Despite persistent motor deficits and dystonia, some developmental progress was observed, as well as reduction in hyperthyroidism.

Discussion/conclusions: This case underscores the importance of early free T3 and fT3/fT4 ratio testing in infants with unexplained developmental delay. Broader inclusion of SLC16A2 in genetic panels and consideration of newborn screening could improve early diagnosis and outcomes in this rare but treatable condition.

Abstract Image

婴儿期MCT8缺乏:早期诊断和筛查的机会。
背景:单羧酸转运蛋白-8-(MCT8)缺乏症或allan - hernton - dudley综合征(AHDS)是一种罕见的x连锁疾病,由SLC16A2基因的致病性变异引起,导致甲状腺激素(主要是T3和T4)跨细胞膜运输受损。由此引起的中枢性甲状腺功能减退和周围性甲状腺功能亢进引起神经发育障碍和甲状腺毒症。尽管有可用的治疗选择,例如使用三碘甲状腺乙酸(TRIAC),但诊断往往被延迟,部分原因是TSH水平正常或基因面板不完整。MCT8缺乏症尚未纳入全球新生儿筛查计划。病例描述:我们报告了一例5个月大的婴儿,在表现为肌肉张力不足、头部控制不足和发育迟缓后,基因诊断为MCT8缺乏症。甲状腺功能检查显示TSH正常,游离T4低,游离T3和游离T3/T4比值明显升高。立即开始使用TRIAC (Emcitate®)治疗,并密切监测药物。尽管存在持续的运动缺陷和肌张力障碍,但仍观察到一些发育进展,以及甲状腺功能亢进的减少。讨论/结论:本病例强调了对不明原因发育迟缓的婴儿进行早期游离T3和fT3/fT4比值检测的重要性。更广泛地将SLC16A2纳入遗传小组,并考虑新生儿筛查,可以改善这种罕见但可治疗疾病的早期诊断和预后。
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来源期刊
International Journal of Neonatal Screening
International Journal of Neonatal Screening Medicine-Pediatrics, Perinatology and Child Health
CiteScore
6.70
自引率
20.00%
发文量
56
审稿时长
11 weeks
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