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Researchers recommend NBAS sequencing in ALF

Researchers in Germany found mutations present in neuroblastoma amplified sequence that helped to identify the origin of acute liver failure in children and recommend the method be performed in any patient with the event, particularly those affected by febrile infection.

“In our study, we initially focused on the genetic similarities in these children to determine a possible cause for their disease,” Tobias B. Haack, MD, PhD, of the Technische Universität München and the Helmholtz Zentrum Munich in Germany, said in a press release.

Tobias B. Haack

Haack and colleagues, including Georg F. Hoffmann, MD, and Holger Prokisch, PhD, performed multiple analyses, beginning with whole exome sequencing. In this process, they performed the sequencing on genomic DNA from five patients with recurrent acute liver failure (RALF).

Holger Prokisch

“Using a frequency filter of minor allele frequency < 0.1% in our in-house database and public databases, we identified six, seven, three, and nine compound heterozygous or homozygous variants in [four of the] individuals,” according to the research. Neuroblastoma amplified sequence (NBAS) was the only gene where researchers identified biallelic mutations.

The researchers further studied 15 other individuals with unresolved RALF and ALF from four additional clinical centers using Sanger sequencing. Of these, six individuals from five families were identified with compound heterozygous mutations in NBAS. Altogether, the 11 individuals were found to carry at least one missense mutation on one allele, according to the research.

“This is the first time that we have been able to establish a link between this gene and liver disease,” Prokisch said in the release. “This discovery could also be interesting for other illnesses.”

Further testing revealed that when the mutations were present in the NBAS gene, only small amounts of the NBAS protein were created. NBAS is involved in cell transport processes that pack proteins in vesicles and transport them across cell compartments, according to the release.

“We were able to show that the faulty protein is more susceptible to heat,” Prokisch said. “This means that when an individual has a fever, there are fewer proteins available for coordinating the transport processes. This, in turn, can have a negative impact on metabolic processes in the liver in an acute situation.”

The researchers said their study results will enable them to focus on the NBAS gene in children with ALF or RALF that is predicated by fever.

“Diagnosis already triggers a specific therapeutic path. Over the years, we have been able to empirically develop a therapy that uses specific drugs as well as sugar and fat infusions [and] these can be immediately administered once a patient is diagnosed,” Hoffmann said in the press release. “We can now use the latest findings to further improve our therapeutic approach.” – by Melinda Stevens

Disclosure: Healio.com/Hepatology was unable to confirm the authors’ financial relationships at the time of publication.

Photo Credits: Uli Benz / TU München and Helmholtz Zentrum München.