Journal of Clinical Pediatrics >

2025 , Vol. 43 >Issue 8: 598 - 603

DOI: https://doi.org/10.12372/jcp.2025.25e0349

Original Article

Thyroxine binding globulin deficiency in three families and review of the literature

  • LI Miaomiao ,
  • PAN Guimei ,
  • LIU Lei ,
  • CHEN Qiong ,
  • LI Yangshiyu ,
  • ZHANG Zixia ,
  • WANG Xi ,
  • DU Mengmeng ,
  • WEI Haiyan ,
  • CHEN Yongxing
Expand
  • 1. Department of Endocrinology and Inborn Error of Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450053, Henan, China
    2. Pediatric Intensive Care Unit, Qingdao Women and Children's Hospital of Qingdao University, Qingdao, 266011, Shandong, China
    3. Pediatric Medical Institute, Children's Hospital Affiliated to Zhengzhou University Henan Children's Hospital, Zhengzhou Children's Hospital, Henan Provincial Key Laboratory for Genetic and Metabolic Disease in Children, Zhengzhou 450018, Henan, China

Received date: 2025-04-03

  Accepted date: 2025-05-26

  Online published: 2025-07-28

Fold

Abstract

Objective To investigate the clinical characteristics and genetic features of thyroid-binding globulin (TBG) deficiency, enhance the accuracy of clinical diagnosis, and avoid misdiagnosis and overtreatment. Methods Members from three different families were subjected to SERPINA7 gene sequencing to explore its genetic basis. Results The variants detected in the three families through whole-exome sequencing occurred in exons, specifically c.712A>G(p.M238V), c.1114delC(p.L372Ffs*23), and c.383-401dup(p.F135Afs*21), with the variants in Family 1 and Family 3 being reported for the first time. Conclusion TBG deficiency does not require special treatment; correct diagnosis and comprehensive disease education are key to the management of this condition. This study identified two new SERPINA7 gene variants, expanding the mutation spectrum of this gene.

Key words： thyroxine binding globulin deficiency; SERPINA7; genetic testing

Cite this article

LI Miaomiao , PAN Guimei , LIU Lei , CHEN Qiong , LI Yangshiyu , ZHANG Zixia , WANG Xi , DU Mengmeng , WEI Haiyan , CHEN Yongxing . Thyroxine binding globulin deficiency in three families and review of the literature[J]. Journal of Clinical Pediatrics, 2025 , 43(8) : 598 -603 . DOI: 10.12372/jcp.2025.25e0349

References

[1] Noguchi T, Yamamori I, Takamatsu J. Hereditary complete thyroxine-binding globulin deficiency: identification by T3 resin uptake test and DNA analysis[J]. Intern Med, 1993 ; 32(1): 6-9.
[2] Connelly KJ, Pierce MJ, Hanna C. Detecting congenital central hypothyroidism by newborn screening: difficulty in distinguishing from congenital thyroxine-binding globulin deficiency[J]. Horm Res Paediatr, 2017, 88(5): 331-338.
[3] Mimoto MS, Refetoff S. Clinical recognition and evaluation of patients with inherited serum thyroid hormone binding protein mutations[J]. J Endocrinol Invest, 2020, 43(1): 31-41.
[4] Chakravarthy V, Ejaz S. Thyroxine-binding globulin deficiency[M]// StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.
[5] Gawandi S, Jothivel K, Kulkarni S. Identification of a novel mutation in thyroxine-binding globulin (TBG) gene associated with TBG-deficiency and its effect on the thyroid function[J]. J Endocrinol Invest, 2022, 45(4): 731-739.
[6] Tojo K, Miura Y, Mori Y. Familial thyroxine-binding globulin deficiency associated with hyperthyroidism[J]. Intern Med, 1995, 34(5): 413-417.
[7] Shirotani T, Kishikawa H, Wake N. Thyroxine-binding globulin variant(tbg-kumamoto): identification of a point mutation and genotype analysis of its family[J]. Endocrinol Jpn, 1992, 39(6): 577-584.
[8] Fang Y, Chen H, Chen Q. Compound hemizygous variants in SERPINA7 gene cause thyroxine‐binding globulin deficiency[J]. Mol Genet Genomic Med, 2021, 9(2): e1571.
[9] Hengeveld RCC, Albersen M, Hadders MAH. A newborn falsely suspected of congenital hypothyroidism due to mutated thyroxine-binding globulin with low binding affinity[J]. Horm Res Paediatr, 2021, 94(1-2): 76-80.
[10] Pappa T, Ferrara AM, Refetoff S. Inherited defects of thyroxine-binding proteins[J]. Best Pract Res Clin Endocrinol Metab, 2015, 29(5): 735-747.
[11] Pappa T, Moeller LC, Edidin DV. A novel mutation in the TBG gene producing partial Thyroxine-binding globulin deficiency (glencoe) identified in 2 families[J]. Eur Thyroid J, 2017, 6(3): 138-142.
[12] Flink IL, Bailey TJ, Gustafson TA. Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA: close homology to the serine antiproteases.[J]. Proc Natl Acad Sci U S A, 1986, 83(20): 7708-7712.
[13] Heo J, Kim S M, Ryu H J. Identification of mutations in the thyroxine-binding globulin (TBG) gene in patients with TBG deficiency in Korea[J]. Endocrinol Metab (Seoul), 2022, 37(6): 870-878.
[14] Chen LD, Lu HJ, Gan YL. Partial thyroxine-binding globulin deficiency in a family with coding region mutations in the TBG gene[J]. J Endocrinol Invest, 2020, 43(12): 1703-1710.
[15] Fang YL, Wang CL, Liang L. Partial thyroxine binding globulin deficiency in test tube infants: report of cases and literature review[J]. Zhonghua Er Ke Za Zhi, 2016 Jun 2; 54(6): 428-432.
[16] Mandel S, Hanna C, Boston B. Thyroxine-binding globulin deficiency detected by newborn screening[J]. J Pediatr, 1993, 122(2): 227-230.
[17] Ferrara AM, Pappa T, Fu J. A novel mechanism of inherited TBG deficiency: mutation in a liver-specific enhancer[J]. J Clin Endocrinol Metab, 2015, 100(1): E173-E181.
[18] Miura Y, Hershkovitz E, Inagaki A, Parvari R, Oiso Y, Phillip M. A novel mutation causing complete thyroxine-binding globulin deficiency (TBG-CD-Negev) among the Bedouins in southern Israel[J]. J Clin Endocrinol Metab. 2000 ; 85(10): 3687-3689.
[19] Soheilipour F, Fazilaty H, Jesmi F. First report of inherited thyroxine-binding globulin deficiency in Iran caused by a known de novo mutation in SERPINA7[J]. Mol Genet Metab Rep, 2016, 8: 13-16.
[20] Torkington P, Harrison RJ, Maclagan NF, Burston D. Familial thyroxine-binding globulin deficiency[J]. Br Med J, 1970, 3(5713): 27-29.
[21] Sklate R, Olcese M, Maccallini G. Novel mutation p. A64D in the Serpina7 gene as a cause of partial Thyroxine-binding globulin deficiency associated with increases affinity in transthyretin by a known p. A109T mutation in the TTR gene[J]. Horm Metab Res, 2013, 45(2): 100-108.
[22] Yamamori I, Mori Y, Miura Y. Gene screening of 23 Japanese families with complete Thyroxine-binding globulin deficiency: identification of a nucleotide deletion at codon 352 as a common cause: identification of a nucleotide deletion at codon 352 as a common cause[J]. Endocr J, 1993, 40(5): 563-569.
[23] 方燕兰, 王春林, 梁黎. 部分性甲状腺激素结合球蛋白缺乏症二例并文献复习[J]. 中华儿科杂志, 2016, 54(6): 428-432.
  Fang Y, Wang C L, Liang L. Partial thyroxine binding globulin deficiency in test tube infants: report of cases and literature review[J]. Zhonghua Erke Zazhi, 2016, 54(6): 428-432.
[24] 王斐, 全会标, 纪群, 等. 完全性甲状腺结合球蛋白缺乏症家系三例及文献复习[J]. 中华内分泌代谢杂志, 2021, 37(7): 653-656.
  Wang F, Quan H B, Ji Q, et al. Three cases of complete thyroxine-binding globulin deficiency in a family and literature review[J]. Zhonghua Neifenmi Daixie Zazhi, 2021, 37(7): 653-656.
[25] Refetoff S, Selenkow H A. Familial thyroxine-binding globulin deficiency in a patient with Turner's syndrome (XO): genetic study of a kindred[J]. N Engl J Med, 1968, 278(20): 1081-1087.
[26] Reutrakul S, Janssen OE, Refetoff S. Three novel mutations causing complete T4-binding globulin deficiency[J]. J Clin Endocrinol Metab, 2001, 86(10): 5039-5044.
[27] Okamoto H, Mori Y, Tani Y, et al. Molecular analysis of females manifesting thyroxine-binding globulin (TBG) deficiency: selective X-chromosome inactivation responsible for the difference between phenotype and genotype in TBG-deficient females[J]. J Clin Endocrinol Metab. 1996, 81(6): 2204-2208.
Options
Outlines

/

〈 〉

Website Copyright © 2018 Journal of Clinical Pediatrics.
Tel: 021-25076489　E-mail: jcperke@126.com
Powered by Beijing Magtech Co. Ltd