Tag Archives: genome

Rapid Genetic Testing in Liver Failure

Posted on by

D Bonser et al. J Pediatr 2023; 260: 113534. Rapid Genome Sequencing Diagnosis in Pediatric Patients with Liver Dysfunction

In this retrospective study with 18 pediatric patients (2019-2021) who presented with pediatric acute liver dysfunction, the authors examined the yield of rapid whole genome sequencing (rWGS). Key findings:

  • Median turnaround was 8 days. In patients with a diagnostic study, an initial report was received in a median of 4 days compared to 10 days with a non-diagnostic study.
  • 7 patients (39%) had diagnostic results including two with ornithine transcarbamylase deficiency, one with Wilson’s disease, one with PFIC type 1, one with infantile liver failure syndrome 2 (due to NBAS gene), one with GSD type 4, and one with infantile liver failure syndrome 1 (due to LARS gene).
  • Five of these patients with abnormal rWGS had liver transplantation evaluation/listing after the test results were received

One annoying aspect of the report is the authors’ attempt to suggest that the diagnostic yield should have been higher if they excluded four patients subsequently thought to have liver dysfunction due to environmental exposures. In a retrospective study, it is easy to second-guess and say that the test could have been used more selectively.

My take: This study shows that rapid whole genome sequencing is a very valuable part of the evaluation of children with severe liver dysfunction. Turnaround times have improved considerably.

Related blog posts

Villefranche-Sur-Mer, France
Cassis, France
Cassis, France

Genomic Sequencing At Birth

Posted on by

The Economist (5/13/22): Full-genome screening for newborn babies is now on the cards (Behind a paywall).

This article delves into the topic of genome screening at birth and its potential role in supplanting current newborn screening.

Rationale: “Doctors have described more than 7,000 rare diseases, generally defined as those affecting fewer than one in 2,000 people. So, though individually unusual, such illnesses are collectively a serious problem—a long-tail of need which is hard to treat because patients are few in number and their symptoms often picked up too late.”

Background: “A government-owned company called Genomics England … will soon start a pilot project intended to sequence the genomes of 200,000 babies. That could presage a national programme.”

Key points:

  • “On May 4th, at a meeting held in London by Genomics England, Rick Scott, the organisation’s chief medical officer, said discussions with parents and doctors had led his team to conclude that people want any genomic-screening programme for newborns to look for a far narrower set of conditions than BabySeq sought. The most appealing tests were for variants associated with a high probability of childhood illness, and which would benefit from early treatment.”
  • “One particular finding, according to David Bick, a clinical geneticist who advises Genomics England, is that parents want certainty. They feel it is no use being told that a child is “fairly likely” to have a condition. Rather, they want a pretty clear “yes” or “no”.”
  • “Many also do not want to know of adult-onset illnesses that their children may one day suffer. This means rejecting tests which might indicate a newborn’s risk, later in life, of contracting cancer, diabetes or Alzheimer’s disease.”
  • Potential problems: learning about degenerative diseases & mental health problems without suitable treatments, data security, mutations with variable phenotypes (variable age of onset and severity)

My take: Genomic screening could broaden the benefits of newborn screening but identifying all of an individual’s genetic flaws is likely to be more detrimental than beneficial at this point.

Related blog posts:

Bandelier National Monument, New Mexico. Caves in the “tuff” volcanic rock.