Recurrent acute liver failure due to NBAS deficiency: phenotypic spectrum, disease mechanisms, and therapeutic concepts

Abstract

Mutations in NBAS cause a complex disease with a wide clinical spectrum ranging from isolated RALF to a multisystemic phenotype. Thermal susceptibility of the syntaxin 18 complex is the basis of fever dependency of ALF episodes. NBAS deficiency is the first disease related to a primary defect of retrograde transport. Identification of NBAS deficiency allows optimized therapy of liver crises and even prevention of further episodes.

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

“…[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. [3]…”

“…and Staufner et al . [12] have examined 16 patients with NBAS mutation. They showed that phenotypic spectrum of NBAS deficiency ranges between isolated recurrent acute liver failure and multisystemic disease, which includes short stature, skeletal dysplasia, optic atrophy, and immunological abnormalities.…”

“…Hepatic phenotype episodes usually start with massive increase in alanine transaminase (ALT) and aspartate transaminase (AST), followed by severe coagulopathy and mild-to-moderate jaundice. [12] However, hypoglycemia, hyperammonemia, and hepatic encephalopathy are transiently observed in some patients. Extrahepatic phenotype of NBAS mutation presents with the following: Short stature, osteopenia, dysmorphism, autoimmune disease, optic atrophy, brain atrophy, and delayed development.…”

“…[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. A review of the literature is also provided.…”

Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society

“…Antipyretic therapy and induction of anabolism including glucose and parenteral lipids may ameliorate the course of liver crises in certain patients as has been noted in NBAS deficiency. 34 Liver transplantation may be indicated in some cases and has been performed in patients with mitochondrial disease. Survival after liver transplantation in some mitochondrial patients approaches that of transplanted patients without mitochondrial disease -although some patients may fare worse (POLG-related disease).…”