R Hegarty et al. J Pediatrics; 236: 124-130. Open Access: Study of Acute Liver Failure in Children Using Next Generation Sequencing Technology

Background: “Despite the progress made over the last 40 years the rate of indeterminate cases [of acute liver failure] remains ~30%”

Methods: The authors identified 41 children (<10 yrs) with DNA sample availability who were admitted to King’s College Hospital, London, with ALF of indeterminate etiology (2000-2018). In addition, trio exome sequencing was performed on 4 children admitted during 2019.

Key Findings:

• Homozygous and compound heterozygous variants were identified in 8 out of 41 children (20%) and 4 out of 4 children (100%) in whom targeted and exome sequencing were carried out, respectively
• The genes involved were NBAS (3 children); DLD (2 children); and CPT1A, FAH, LARS1, MPV17, NPC1, POLG, SUCLG1, and TWINK (1 each). Variants in NBAS and mitochondrial DNA maintenance genes were the most common findings.

My take: Genetic testing for underlying metabolic/metabolic disorders is important to further determine the reasons for ALF. Given the potential need for liver transplantation, obtaining these results quickly will be crucial. In addition, interpretation of the results in some cases will be difficult.

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