A case series highlighting structured hematological, biochemical and molecular approach to clinical oral iron refractoriness in children: A pressing need for a 3-tier system for classification of variants in TMPRSS6 gene

被引：5
作者：
Sharma, Pankaj [1 ]
Bhatia, Prateek [1 ]
Singh, Minu [1 ]
Das, Reena [2 ]
Jain, Richa [1 ]
Bansal, Deepak [1 ]
Attri, Savita Verma [3 ]
Trehan, Amita [1 ]
机构：
[1] Dept Pediat, Pediat Hematol Oncol Unit, Chandigarh, India
[2] Post Grad Inst Med Educ & Res, Dept Hematol, Chandigarh, India
[3] Adv Pediat Ctr, Dept Pediat, Pediat Biochem, Chandigarh, India
来源：
BLOOD CELLS MOLECULES AND DISEASES | 2021年 / 89卷
关键词：
URIDA; Iron; TMPRSS6; SNPs; HEPCIDIN;
D O I：
10.1016/j.bcmd.2021.102569
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
In current study, we discuss clinical oral iron refractoriness cases and highlight need for a classification system to define TMPRSS6 gene variants. Out of 231 cases of microcytic hypochromic anemia screened (Sept 2019-Dec 2020), 17 cases (7.35%) with unexplained iron refractoriness (URIDA) phenotype were enrolled after ruling out secondary causes and compliance related issues. 11 (65%) had absent/negligible response (0-0.4 g/dl Hb rise) while 6 (35%) partial (0.5-0.9 g/dl Hb rise) response to initial iron trial at 4-8 weeks. Of these 17 cases, inappropriate hepcidin levels (normal-high) were noted in 11/15 (73%) tested. TSAT/Hepcidin ratio was low in 13/15 (87%). Genetic analysis of TMPRSS6 gene by NGS revealed variations in 15/17 (88%) cases. 10/15 cases with variations harbored a common splice site INDEL that was noted to be pathogenic SNP (MAF-0.19) on casecontrol association study in combination with other known missense SNPs with an odds ratio of 6.38 and relative risk 2.66 (p- < 0.01).
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页数：10
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