Gao Jinzhi, Hu Xiaolin, Hu Wei, Sun Xuan, Chen Ling
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Transl Pediatr. 2022 Jun;11(6):1050-1057. doi: 10.21037/tp-21-574.
Trichohepatoenteric syndrome (THES) is a rare autosomal recessive genetic disease caused by pathogenic mutations in or gene. The presentation is variable, including intractable diarrhea, woolly hair abnormality, immune dysfunction, intrauterine growth restriction (IUGR), facial dysmorphism, and sometimes liver and skin abnormalities. Although four Chinese children affected with THES syndrome 1 have been described in Singapore, Taiwan (China) and Malaysia, to our knowledge, this is the first report of a patient with THES in Mainland China, harboring classical platelets features, clinical course, and novel mutations in gene.
The male infant had symmetrical IUGR, and was born at 37 weeks with a birth weight of 1,480 g. He presented with feeding difficulties and vomiting from the 12 day after birth during the stay in neonatal intensive care unit, and had excessive diarrhea from the 21st day after birth. From the 35 day after birth, even slightly hypotonic oral rehydration solution caused watery stools. The blood glucose level was lower than 3.3 mmol/L even when the glucose infusion rate was up to 14 mg/kg/min on the parenteral alone, which has not been reported in previous literature. Normal α-granules were observed occasionally in THES platelets. Whole-exome sequencing analysis identified compound heterozygous mutations (c.4130C > G: p.S1377X) and (Exon11-13 del) in the gene, which had been inherited from his father and mother, respectively. To our knowledge, the above mutations have not been described in any database or previous literature. Total parenteral nutrition was employed as mainstay of therapy, and hydrocortisone (1 mg/kg/dose, every 4 hours) was used to maintain blood glucose levels. The patient's final prognosis was poor after discharged from the hospital.
This case presented with mild platelet abnormality and intractable hypoglycemia, which extends the known mutation and phenotype of THES. The clinical features of Chinese patient are consistent with other ethnicity. Molecular diagnosis is useful for patients with unexplained intractable diarrhea, which puts an end to a long diagnostic odyssey.
毛发肝肠综合征（THES）是一种罕见的常染色体隐性遗传病，由 或 基因的致病性突变引起。其表现多样，包括顽固性腹泻、羊毛状毛发异常、免疫功能障碍、宫内生长受限（IUGR）、面部畸形，有时还伴有肝脏和皮肤异常。尽管在新加坡、中国台湾和马来西亚已报道了 4 例患有 THES 综合征 1 的中国儿童，但据我们所知，这是中国大陆首例关于 THES 患者的报道，该患者具有典型的血小板特征、临床病程及 基因的新突变。
该男婴患有对称性宫内生长受限，37 周出生，出生体重 1480 克。在新生儿重症监护病房住院期间，出生后第 12 天出现喂养困难和呕吐，出生后第 21 天开始出现严重腹泻。出生后第 35 天，即使是轻度低渗口服补液盐也会导致水样便。即使仅通过肠外途径给予葡萄糖输注速率高达 14 毫克/千克/分钟时，血糖水平仍低于 3.3 毫摩尔/升，此前文献中未见此报道。在 THES 血小板中偶尔观察到正常的α颗粒。全外显子测序分析在 基因中鉴定出复合杂合突变（c.4130C > G：p.S1377X）和（外显子 11 - 13 缺失），分别遗传自其父亲和母亲。据我们所知，上述突变在任何数据库或先前文献中均未被描述。采用全肠外营养作为主要治疗方法，并使用氢化可的松（1 毫克/千克/剂量，每 4 小时一次）维持血糖水平。患者出院后的最终预后较差。
该病例表现为轻度血小板异常和顽固性低血糖，扩展了已知的 THES 突变和表型。中国患者的临床特征与其他种族一致。分子诊断对不明原因的顽固性腹泻患者有用，结束了漫长的诊断历程。
