Gil-Margolis Merav, Mozer-Glassberg Yael, Tobar Ana, Ashkenazi Shai, Zeharia Avraham, Marom Daphna
Pediatrics A, Schneider Children's Medical Center of Israel.
Institue of Pediatric Gastroenterology, Nutrition and Liver, Schneider Children's Medical Center of Israel.
Harefuah. 2018 Jan;157(1):52-57.
Bi-allelic mutations in the TRMU gene cause reversible infantile liver failure. Little is known about extra-hepatic manifestations in these patients.
Two infants, aged 4 and 5 months, presented with progressive life threatening liver failure, characterized by lactic acidosis, highly elevated alpha-fetoprotein and recurrent hypoglycemia. Both showed significant extra-hepatic findings, including: hypothyroidism, macrocytic anemia and microcephaly. Both were of Jewish Yemenite descent and homozygous for Y77H mutation in the TRMU gene.
TRMU bi-allelic mutations cause severe life-threatening liver failure. Extra-hepatic involvement is common and should be evaluated. Spontaneous resolution and recovery occurs in most patients with a remarkably good long-term prognosis. Liver failure in a Jewish-Yemenite infant should prompt early genetic testing for TRMU Y77H mutation. Pediatricians should be aware of this disease and the common mutation in Israel.
Nineteen additional patients were described in the literature, of whom 13 were from Israel; 6/19 (31%) manifested extra-hepatic involvement, namely: myopathic weakness, cardiomyopathy, renomegaly and proteinuria, bulbar dysfunction, cerebral white matter changes and abnormal growth including microcephaly. Mortality was 24% (5/21). Survivors (16/21, 76%) showed complete recovery and resolution of clinical, laboratory and histologic abnormalities. Most Israeli patients (10/15) were of Jewish-Yemenite ancestry. Homozygous Y77H genotype was exclusive to this patient subgroup and was associated with a 100% survival and recovery rate.
TRMU基因的双等位基因突变会导致可逆性婴儿肝衰竭。关于这些患者的肝外表现知之甚少。
两名年龄分别为4个月和5个月的婴儿出现进行性危及生命的肝衰竭，其特征为乳酸酸中毒、甲胎蛋白高度升高和反复低血糖。两人均有明显的肝外表现，包括：甲状腺功能减退、大细胞性贫血和小头畸形。两人均为也门裔犹太人，且TRMU基因Y77H突变纯合。
TRMU双等位基因突变会导致严重危及生命的肝衰竭。肝外受累很常见，应进行评估。大多数患者会自发缓解和康复，长期预后非常好。也门裔犹太婴儿出现肝衰竭应尽早进行TRMU Y77H突变的基因检测。儿科医生应了解这种疾病以及以色列常见的突变。
文献中还描述了另外19名患者，其中13名来自以色列；19例中有6例（31%）表现出肝外受累，即：肌病性肌无力、心肌病、肾肿大和蛋白尿、延髓功能障碍、脑白质改变以及包括小头畸形在内的生长异常。死亡率为24%（5/21）。幸存者（16/21，76%）临床、实验室和组织学异常均完全恢复。大多数以色列患者（10/15）为也门裔犹太人。纯合Y77H基因型为此患者亚组所特有，且与100%的生存率和康复率相关。
