Biallelic Mutations in NBAS Cause Recurrent Acute Liver Failure with Onset in Infancy

Abstract

Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever.

Neuroblastoma amplified sequence gene mutation: A rare cause of recurrent liver failure in children

“…and Staufner et al . [12] taken together with the observation in our patient suggest that most patients had onset in the first 2 years of life, with episodic liver failure in these patients precipitated by intercurrent febrile illness, and liver function recovering completely with conservative management in the interval. However, our patient mostly presented with recurrent episodes of hepatitis (liver crisis without liver failure) during intercurrent febrile illness.…”

“…[1] ILFS type 2 is caused by a mutation in the NBAS gene on the chromosome 2p24. [2] ILFS type 1 is caused by mutation in the Leucyl-tRNA synthetase (LARS) gene on the chromosome 5q32.…”

“…[1] ILFS type 2 is an autosomal recessive disorder diagnosed by mutations in the NBAS mutation gene found by whole-exome sequencing. [2] We report the case of a 4-year-old girl presenting with recurrent hepatitis found to have NBAS mutation.…”

Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function

“…C17orf89 transcript abundance in control and patient lines was measured as described previously (Haack et al, 2015). …”

ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment

“…One example of an unmet medical need is idiopathic liver disease, which remains a challenge in both pediatric and adult hepatology. We and others have shown the utility of whole-exome sequencing in the diagnosis of such patients (2)(3)(4)(5)(6). Children with unexplained liver disease who are the offspring of a consanguineous union are excellent candidates for recessive disease-causing mutations.…”