Background: Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates and infants with the prevalence of 1:2,500 to 4,000 newborns. It can be classified into primary and central hypothyroidism. Thyroglubulin (Tg) deficiency is one of the cause of primary hypothyroidism. Thyroglobulin is synthesized only in thyroid gland and required for the biosynthesis of thyroid hormone. The gene thyroglobulin (TG) is composed of 48 exons and located at 8q24.2-8q24.3. More than 50 mutations have been identified in the human TG gene. Patient with TG mutation can be characterized by goitrous congenital hypothyroidism with absent or low levels of serum Tg. Case: A 15-day-old male newborn was referred to our hospital with elevated TSH (65.72 uIU/mL) in neonatal screening test. He was born at 38 weeks 6 days of GA with 3.4kg of birth weight. His weight, height, and head circumference were 3.9 kg (20 percentile), 54.8 cm (70 percentile), and 35 cm (25 percentile), respectively. Follow-up thyroid function test (TFT) showed more elevated TSH levels (＞100.0 mIU/L). Serum total T3, free T4, and Tg levels were 73.17 ng/dL, 0.228 ng/dL, and 5.53 ng/mL, respectively. Thyroid sonography revealed increased size and blood flow of thyroid gland in the normal position. He started taking levothyroxine 40 ug (10 ug/kg) daily under the diagnosis of CH. After the medication, serum levels of free T4, total T3, and TSH became normalized and Tg level turned into less than 1 ng/mL. Euthyroid state was maintained with medication during follow-up period. For the specific genetic diagnosis, Sanger sequencing of gene TSHR (TSH receptor) and diagnostic exome sequencing (DES) of 23 genes associated with CH were performed at his age of 34 months using his and his parents\' DNAs extracted from blood. Two mutations of gene TG were found, One was previously reported c.3790 T＞C (p.Cys1264Arg) missense mutation in exon 17 inherited from his mother and the other one was novel c.4057C＞T (p.Gln1353*) nonsense mutation in exon 19 inherited from his father. Now he is 5.5 years old and taking levothyroxine 75ug (4 ug/kg) daily. His intelligence is good with weight of 22.2kg (80 percentile) and height of 117.8 cm (90 percentile). Conclusion: Here we report a case of primary congenital hypothyroidism with Tg deficiency caused by compound heterozygous mutations of TG gene.