Allan–Herndon–Dudley syndrome (AHDS) caused by a novel SLC16A2 gene mutation showing severe neurologic features and unexpectedly low TRH-stimulated serum TSH

Boccone, Loredana; Mariotti, Stefano; Dessì, Valentina; Pruna, Dario; Meloni, Antonella; Loudianos, Georgios

doi:10.1016/j.ejmg.2010.08.001

Cited by 35 publications

(52 citation statements)

References 23 publications

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“…1B) Nevertheless, it was only a partial resistance since TSH levels (and subsequently FT 4 levels) were remarkably suppressed in response to the gradual elevation in T 3 levels during low-and especially highdose LT 3 treatment (Table 1). Furthermore, basal T 3 imposed some suppressing effect on TSH elevation during TRH stimulation test, an observation that was reported by others (17,28). In the human pituitary gland, MCT8 is expressed in the folliculostellate cells rather than the TSH-producing cells (29).…”

Section: Discussionmentioning

confidence: 52%

A child with a deletion in the monocarboxylate transporter 8 gene: 7-year follow-up and effects of thyroid hormone treatment

Zung

Visser²,

Uitterlinden³

et al. 2011

European Journal of Endocrinology

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Objective: The monocarboxylate transporter 8 (MCT8; SLC16A2) has a pivotal role in neuronal triiodothyronine (T 3 ) uptake. Mutations of this transporter determine a distinct X-linked psychomotor retardation syndrome (Allan-Herndon-Dudley syndrome (AHDS)) that is attributed to disturbed thyroid hormone levels, especially elevated T 3 levels. We describe the genetic analysis of the MCT8 gene in a patient suspected for AHDS and the clinical and endocrine effects of L-thyroxine (LT 4 ) or liothyronine (LT 3 ) treatment intending to overcome the T 3 uptake resistance through alternative transporters. Methods: The six exons of the MCT8 gene were amplified individually by PCR. As multiple exons were missing, the length of the X-chromosomal deletion was determined by a dense SNP array, followed by PCR-based fine mapping to define the exact borders of the deleted segment. The clinical and endocrine data of the patient during 6.5 years of LT 4 treatment and two periods (3 months each) of low-and high-dose LT 3 were evaluated. Results: A partial deletion of the MCT8 gene (comprising five of six exons) was detected, confirming the suspected AHDS. MCT8 dysfunction was associated with partial resistance to T 3 at the hypothalamus and pituitary level, with normal responsiveness at the peripheral organs (liver and cardiovascular system). Thyroid hormone administration had no beneficial effect on the neurological status of the patient. Conclusion: We identified a 70 kb deletion encompassing exons 2-6 of the MCT8 gene in our AHDS patient. Both LT 4 and LT 3 administration had no therapeutic effect. Alternatively, treatment of AHDS patients with thyroid hormone analogs should be considered.

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Section: Discussionmentioning

confidence: 52%

A child with a deletion in the monocarboxylate transporter 8 gene: 7-year follow-up and effects of thyroid hormone treatment

Zung

Visser²,

Uitterlinden³

et al. 2011

European Journal of Endocrinology

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“…A prominent and common feature in MCT8 deficient patients is the failure to thrive, which may require in some cases a gastric feeding tube. Possible reasons for low weight and muscle wasting are difficulty swallowing on neurological basis, and increased metabolism due to the thyrotoxic state of peripheral tissues caused by the high serum T 3 levels [82,[85][86][87].…”

Section: Clinical Features and Course Of The Disordermentioning

confidence: 99%

Syndromes of Reduced Sensitivity to Thyroid Hormone

Weiss

Dumitrescu

Refetoff

2010

Genetic Diagnosis of Endocrine Disorders

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“…At the age of 4, the patient started having dyskinetic episodes lasting a few seconds, which occurred during both awake and sleep states without apparent triggers. These attacks have already been reported in other patients, 13,[15][16][17] which were described as paroxysmal kinesigenic dyskinesia episodes that may occur as a response to an emotional or physical trigger. 13 The hallmark of AHDS is the typical thyroid function profile consisting of elevated FT3, normal/low or low FT4 and normal or slightly elevated TSH.…”

Section: Discussionmentioning

confidence: 90%

“…Our case differs in this regard from other cases described, in which the patients' cardiac results were not diagnostic. 16,24 On the other hand, and according to what has previously been published, 11,12,17 the normal growth and the correlation between bone age and chronological age suggest that MCT8 does not play a crucial role in the transport of T3 to bone cells. 11,12,17 Despite T3 deficiency at the neuronal level, a state of peripheral hyperthyroidism may be explained by the possible presence of TH transports in those tissues.…”

Section: Discussionmentioning

confidence: 96%

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Severe neurological abnormalities in a young boy with impaired thyroid hormone sensitivity due to a novel mutation in the MCT8 gene

Rego

Lado

Rodríguez

et al. 2017

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Monocarboxylate transporter 8 (MCT8) is an active and specific thyroid hormone transporter into neurons. MCT8 mutations cause an X-linked condition known as Allan-Herndon-Dudley syndrome and are characterized by impaired psychomotor development and typical abnormal thyroid function. we describe a 10-year-old boy with severe cognitive disability, axial hypotonia, spastic quadriplegia and sporadic dyskinetic episodes. He initially presented with thyroid dysfunction (high FT3, low rT3, low FT4 and normal TSH) and generalized retardation of the cerebral and cerebellar myelination in brain magnetic resonance imaging. The clinical and laboratory findings led to sequencing of the SLC16A2/MCT8 gene, which identified a novel missense mutation in exon 5. The study of peripheral markers of thyroid function suggests a paradoxical state of thyrotoxicosis in some peripheral tissues. Our patient had a typical clinical presentation at birth but because of the rarity of his disease his diagnosis was not made until the age of 7. The delay can also be explained by the omission of the free T3 assay in the first thyroid evaluation performed. This case therefore highlights the possible benefit of including the T3 assay in the study of patients with severe psychomotor disability of unknown etiology, thus eliminating extra costs for unnecessary complementary diagnostic tests.

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Allan–Herndon–Dudley syndrome (AHDS) caused by a novel SLC16A2 gene mutation showing severe neurologic features and unexpectedly low TRH-stimulated serum TSH

Cited by 35 publications

References 23 publications

A child with a deletion in the monocarboxylate transporter 8 gene: 7-year follow-up and effects of thyroid hormone treatment

A child with a deletion in the monocarboxylate transporter 8 gene: 7-year follow-up and effects of thyroid hormone treatment

Syndromes of Reduced Sensitivity to Thyroid Hormone

Severe neurological abnormalities in a young boy with impaired thyroid hormone sensitivity due to a novel mutation in the MCT8 gene

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