Delayed Myelination Pattern and an Abnormal Thyroid Profile Caused by a Novel Mutation in the SLC16A2 Gene
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SCIENTIFIC LETTER
Delayed Myelination Pattern and an Abnormal Thyroid Profile Caused by a Novel Mutation in the SLC16A2 Gene Indar Kumar Sharawat 1 & Renu Suthar 2
&
Arushi Gahlot Saini 2 & Sameer Vyas 3
Received: 15 April 2020 / Accepted: 21 July 2020 / Published online: 6 August 2020 # Dr. K C Chaudhuri Foundation 2020
To the Editor: A 5-and a ½-y-old boy presented with delayed attainment of developmental milestones and intermittent twisting postures of the body from early infancy. He had progressively increasing stiffness in the limbs and episodes of back arching. There was no history suggestive of seizures, abnormal body odor, skin rashes, constipation, diaper staining, and fluctuation in his symptoms. He was born to a nonconsanguineous couple without any adverse perinatal event. Family history was non-contributory, and he has an 8-mo-old neurologically normal younger sister. Examination revealed severe developmental delay, marked wasting, stunting (weight- 12 kg at -7.1 Z score, and length- 99 cm at -4.8 zscore), and small head (49.2 cm at -2.7 Z score), dental carries, horizontal gaze nystagmus, perioral dyskinesia, cervical and appendicular dystonia, axial hypotonia with decreased muscle mass and preserved muscle stretch reflexes. An MRI of the brain showed delayed myelination pattern (Fig. 1). Investigations revealed normal TSH (2.43 μU/L; normal: 0.35–5.5), low T4 (1.8 ng/dl; normal: 4.5–12.7), and elevated T3 (2.54 ng/dl; normal: 0.6–1.8) levels. Free T4 levels were reduced (0.5 ng/dl, normal 0.86–1.4) and free T3 levels were elevated (7.61 pg/ml, normal 3.3–4.80). Clinical exome sequencing using next-generation sequencing using the Illumina sequencing platform showed a novel likely pathogenic hemizygous, missense variation in exon 3 of the SLC16A2 gene (c.604G > A) suggesting the diagnosis of Allan-Herndon Dudley syndrome (NM_006517). The variant * Renu Suthar [email protected] 1
Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh Uttarakhand India
2
Pediatric Neurology Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh 160012 India
3
Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh India
was found to be deleterious by bioinformatics algorithms such as Polyphen, LRT_pred, SIFT and Mutation Taster. Sanger sequencing confirmed the variant. Maternal thyroid profile showed low free serum T4 (0.74 ng/dl, range 0.89–1.76), normal free serum T3 (3.55 pg/ml, range 2.3–4.2) and normal serum TSH (1.92 μIU/ml, range 0.55–4.78). He was started on syndopa, baclofen, tetrabenazine, and trihexyphenidyl with minimal benefit. Allan–Herndon–Dudley syndrome (AHDS) is a rare Xlinked inherited disorder caused by a disease-causing variation in the SLC16A2 gene which encodes monocarboxylate transporter 8 (MCT-8) protein [1]. MCT-8 is a specific thyroid hormone transporter crucial for the transport of T3 and T4 in the brain. The thyroid hormone (TH
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