1例希特林缺陷病合并丙酮酸激酶缺乏症的临床特征和基因特点

Clinical and Genetic Variation Characteristics of A Child with Citrin Deficiency and Pyruvate Kinase Deficiency

目的探讨希特林缺陷病合并丙酮酸激酶缺乏症患儿的临床表型及基因型特点。方法总结本院1例希特林缺陷病合并丙酮酸激酶缺乏症患儿诊断、治疗及随访。结果患儿出生后即出现重度溶血性贫血、高胆红素血症、棘形红细胞增多。血串联质谱检测显示瓜氨酸增高,遂予以无乳糖奶粉喂养、输血等治疗。患儿1月龄后再次出现重度贫血。全外显子组测序检测结果显示:该患儿携带PKLR基因c.1418T>A/c.1248_1269delinsGCTCCCT复合杂合突变和SLC25A13基因c.852_855delTATG纯合突变,因此被诊断为希特林缺陷病合并丙酮酸激酶缺乏症。患儿需要约1.5月/次的反复输血治疗,生长发育正常,但伴肝脾肿大、血清铁蛋白增高,2岁开始口服祛铁治疗。结论希特林缺陷病合并丙酮酸激酶缺乏症的案例在临床上非常罕见,患儿出生后表现重度贫血,棘形红细胞数目明显增加,输血依赖,需要早期干预。

Objective To investigate the clinical and genetic characteristics of a child with Citrin deficiency and pyruvate kinase deficiency.Methods We summarized the diagnosis,treatment and follow-up of the patient with Citrin deficiency and pyruvate kinase deficiency in Women and Children's Hospital,School of Medicine,Xiamen University.Results The patient was born with severe hemolytic anemia,hyperbilirubinemia,and acanthocytosis.Tandem mass analysis of blood sample showed that the concentration of Citrulline(Cit)increased.He was accepted with lactose free milk feeding and blood transfusion.Severe anemia occurred again after 1 month.Whole exome sequencing results showed that this child carried c.1418 T>A plus c1248_1269 delinsGCTCCCT compound heterozygous mutation in PKLR and c.852_855 delTATG homozygous mutation in SLC25A13.Consequently,he was diagnosed with Citrin deficiency and pyruvate kinase deficiency.The patient needed to receive blood transfusion for once about every 45 days.Meanwhile,we found his serum ferritin was increased with hepatosplenomegaly.Oral iron removal treatment was began at the age of 2.Conclusion It is very rare for an individual to suffer from both Citrin deficiency and pyruvate kinase deficiency.Anemia was the first manifestation after birth with increased acanthocytosis significantly.Early intervention is very important.