Merav Gil-Margolis1, Yael Mozer-Glassberg2,3, Ana Tobar4,3, Shai Ashkenazi5,3, Avraham Zeharia6,3, Daphna Marom1,3. 1. Pediatrics A, Schneider Children's Medical Center of Israel. 2. Institue of Pediatric Gastroenterology, Nutrition and Liver, Schneider Children's Medical Center of Israel. 3. Sackler Faculty of Medicine, Tel Aviv University. 4. Institute of Pathology, Rabin Medical Center, Petach Tikwa. 5. Unit of Pediatric Infectious Diseases, Schneider Children's Medical Center of Israel. 6. Pediatric Day Department, Schneider Children's Medical Center of Israel.
Abstract
INTRODUCTION: Bi-allelic mutations in the TRMU gene cause reversible infantile liver failure. Little is known about extra-hepatic manifestations in these patients. BACKGROUND: 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. CONCLUSIONS: 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. DISCUSSION: 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.
INTRODUCTION: Bi-allelic mutations in the TRMU gene cause reversible infantile liver failure. Little is known about extra-hepatic manifestations in these patients. BACKGROUND: 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. CONCLUSIONS: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 TRMUY77H mutation. Pediatricians should be aware of this disease and the common mutation in Israel. DISCUSSION: 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.
Authors: Chaya N Murali; Claudia Soler-Alfonso; Kathleen M Loomes; Amit A Shah; Danielle Monteil; Carmencita D Padilla; Fernando Scaglia; Rebecca Ganetzky Journal: Mol Genet Metab Date: 2021-01-14 Impact factor: 4.797
Authors: Júlia Sala-Coromina; Lucía Dougherty-de Miguel; Javier de Las Heras; Amaia Lasa-Aranzasti; Elena Garcia-Arumi; Lidia Carreño; Jose Antonio Arranz; Clara Carnicer; María Unceta-Suárez; Angel Sanchez-Montañez; Laura Gort; Frederic Tort; Mireia Del Toro Journal: Mol Genet Metab Rep Date: 2020-12-15