Two siblings with acute necrotizing encephalopathy associated with variants of LARS1.
Takeshi UeharaEijun SekiYutaka NonodaTatsuro KumakiYu TsuyusakiNoriko AidaYumi EnomotoKenji IshikuraKenji KurosawaPublished in: American journal of medical genetics. Part A (2024)
Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy of unknown etiology. The underlying mechanisms are highly heterogeneous, often including genetic backgrounds. Variants of LARS1, encoding the leucyl-tRNA synthetase 1, are responsible for infantile liver failure syndrome 1. We describe two siblings with ANE caused by compound heterozygous variants of LARS1. Patient 1 was a 17-month-old girl. She presented with generalized seizure and liver dysfunction due to influenza type A infection. Brain magnetic resonance imaging on day 4 of onset showed diffuse high-intensity signals consistent with ANE. She died on day 10. Patient 2, a younger male sibling of patient 1, had mild to moderate developmental delay and growth failure at the age of 18 months. He showed a markedly elevated level of transaminases triggered by infection with human herpesvirus 6. On day 4 of onset, he had generalized seizures. Brain computed tomography showed a diffuse symmetrical hypodensity consistent with ANE. He died on day 7. Whole exome sequencing identified the compound heterozygous variants in LARS1 (NM_020117.11) as c.83_88delinsAATGGGATA, p.(Arg28_Phe30delinsLysTryAspIle) and c.1283C>T, p.(Pro428Leu) in both siblings. The severe neurologic phenotype, found in our patients, reflects the complicated pathogenesis of LARS1-related disorder.
Keyphrases
- liver failure
- early onset
- copy number
- high intensity
- case report
- computed tomography
- magnetic resonance imaging
- hepatitis b virus
- end stage renal disease
- intellectual disability
- endothelial cells
- white matter
- drug induced
- ejection fraction
- multiple sclerosis
- newly diagnosed
- oxidative stress
- resting state
- respiratory failure
- low grade
- genome wide
- peritoneal dialysis
- chronic kidney disease
- photodynamic therapy
- prognostic factors
- anti inflammatory
- aortic dissection
- intensive care unit
- blood brain barrier
- temporal lobe epilepsy