Endocrinological investigations in two cases of MCT8 abnormality with novel mutations in the SLC16A2 gene

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 596-623-Case Reports: Pediatric Endocrinology & Metabolism
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-618
Erina Ono*1, Masamichi Ariga1, Sakiko Oshima1, Mika Hayakawa1, Masayuki Imai1, Yukikatsu Ochiai1, Satoshi Matsushima2, Ichiro Miyata2, Noriyuki Namba3, Keiichi Ozono3 and Hiroyuki Ida2
1Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan, 2The Jikei University School of Medicine, Tokyo, Japan, 3Osaka Univ Grad Schl of Med, Suita Osaka, Japan
Background: Monocarboxylate transporter 8 (MCT8) is a potent thyroid hormone transporter which facilitates T3 uptake into central neurons. In patients with mutations in the MCT8 (SLC16A2) gene, thyroid function tests show elevated FT3, lowered FT4 and borderline-slightly high TSH levels in the blood. This disease is characterized by X-linked severe mental retardation, reduced muscle mass, hypotonia and quadriplegia or spastic paraplegia. We recently experienced two male cases of MCT8 abnormality with novel mutations in the SLC16A2 gene, and performed endocrinological investigations for them.

Clinical cases: Case 1 is an 8-year-old boy. Pregnancy and delivery were uneventful. There was no family history of thyroid disorders or delay in neurological development. Poor weight gain and hypotonia with poor head control were pointed out at age 4 months. Brain MRI showed delayed myelination at age 1 year. At present, severe mental retardation, poor head control, reduced muscle mass, hypotonia and short stature are found. On current thyroid function test, serum levels of TSH, FT3 and FT4 were 2.44 mIU/ml, 4.2 pg/ml and 0.6 ng/dl, respectively. Case 2 is a 20-year-old boy. Pregnancy and delivery were not complicated. There was no family history of thyroid disorders or delay in neurological development. Growth and developmental delay were pointed out, and brain MRI showed delayed myelination at age 1 year. At present, severe mental retardation, inadequate head control, reduced muscle mass, quadriplegia and short stature are found. Recent thyroid function revealed serum levels of TSH, FT3 and FT4 of 7.09 mIU/ml, 6.2 pg/ml and 0.3 ng/dl, respectively.

SLC16A2 gene analysis: SLC16A2 gene analysis was performed for our two patients, because MCT8 abnormality was suspected. A missense hemizygous mutation in exon 4 (p.R445S) of Case 1 and a missense hemizygous mutation in exon 1 (p. G196E) of Case 2 were identified. Those were novel mutations.

Endocrinological studies: Thyroid function tests showed the typical pattern for MCT8 abnormality in both Case 1 and 2. However, euthyroid was detected in early childhood for either case. TRH test revealed the pituitary hypothyroid pattern of TSH in Case 1. Brain MRI and cervical echogram demonstrated atrophy of the pituitary and thyroid glands. In Case 2, GH deficiency and Gonadotropin deficiency were detected, and TRH test revealed the primary hypothyroid pattern of TSH. Brain MRI and cervical echogram demonstrated atrophy of the pituitary gland and enlargement of the thyroid gland.

Conclusion: Our findings suggest that thyroid status of MCT8 abnormality is changeable according as the time of examination, and therefore regular thyroid function test is necessary for suspicious patients of MCT8 abnormality. Additionally, we should take care in that various patterns are found with regard to pituitary dysfunction and the size of thyroid gland in MCT8 abnormality.

Nothing to Disclose: EO, MA, SO, MH, MI, YO, SM, IM, NN, KO, HI

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