Ege University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey**
İzmir Tepecik Training and Research Hospital, Genetic Diseases Diagnosis Center, İzmir, Turkey
Thyroid receptor alpha (THRA) gene mutation causes thyroid hormone resistance syndrome characterized by near normal thyroid function tests and tissue-specific hypothyroidism.
Case: A 4-year-old male patient was admitted with short stature, motor-mental retardation, and constipation. Motor-mental retardation has been assessed at the age of one year and no etiologic cause was found. In past medical history, he was born at 38 weeks gestational age with a birth weight of 2900 g. His motor-mental milestones were delayed. He had transient hypogammaglobulinemia. Mother and father were first-degree relatives. In his physical examination, height, weight, and head circumference were 17.4 kg (SDS: -0.12), 96.4 cm (SDS: -2.47), and 54.5 cm (SDS: 2.08), respectively. Pubertal stage was A1P1, testes were 2+2 mL palpable. He had edema in the eyelids, face was coarse, and umbilical hernia was found. In the lab exam, Hb was 10.4 g/dL, MCV 88.5 fL, RDW 14.7%, electrolytes, liver and kidney function tests were normal, CK and CK-MB were 396 IU/L (41-277) and 55.3 U/L (0-24), respectively. fT3 was 5.04 pg/mL (2.3-4.2), fT4 0.93 ng/dL (0.89-1.76), and TSH was 3.89 µIU/mL (0.35-5.5); bone age was 2 years. Craniography revealed thickness of the scalp. Phenotypically hypothyroid findings and at moderate elevation of fT3 levels, normochrome normocytic anemia and elevation of CK and CK-MB levels were consistent with primary thyroid hormone resistance. In the mutation analysis, a novel de novo p.G291S heterozygous mutation in the THRA gene was detected. Na-L thyroxin replacement therapy was initiated.
THRA gene mutation should be considered in patients who are clinically hypothyroid with increased/moderately increased fT3, decreased/normal fT4, normal TSH levels, and increased muscle enzymes.