Researchers identified guidelines-consistent panels of 37 and 74 genetic conditions following evidence-based analyses of criteria, including long chain fatty acid oxidation disorders (LCFAODs) such as primary carnitine deficiency, carnitine palmitoyltransferase 2 deficiency, and very long-chain acyl-CoA dehydrogenase deficiency, as published in Genetics in Medicine.
Other guideline-consistent conditions identified were sickle cell disease, cystic fibrosis (CF), spinal muscular atrophy (SMA), Pompe disease, and Duchenne muscular dystrophy. Clear criteria are needed for the design of carrier screening panels to ensure the conditions meet a certain level of quality and are consistent, the authors said.
“The panels identified here are consistent with evidence-based interpretations of ACOG [American College of Obstetricians and Gynecologists] and [American College of Medical Genetics and Genomics] panel design criteria and more effectively identify carriers and [at-risk couples], regardless of their race/ethnicity,” they wrote.
Read more about LCFAOD diagnosis
Currently, the ACOG recommends that only CF and SMA should be screened in all couples regardless of race/ethnicity.
Here, a team of researchers led by Haywood Brown, MD, from the Morsani College of Medicine at the University of South Florida in Tampa used carrier frequencies in more than 460,000 individuals across 11 races/ethnicities to assess the carrier frequency of 176 genetic diseases.
With the aim to identify guidelines-consistent carrier screening panels, they found that 40 conditions had carrier frequencies of 1 in 100 or more, and 75 conditions had carrier frequencies of 1 in 200 or more. Of these conditions, 175 had well-defined phenotypes and 165 met 1 or more criteria and had early-life onsets.
In total, 37 conditions met conservative thresholds of a carrier frequency of at least 1 in 100. Also, 74 conditions met permissive thresholds of a carrier frequency of at least 1 in 200. Both disease panels were therefore identified as being guidelines-consistent.
The 7 criteria suggested by the ACOG included having a well-defined phenotype, an early-life onset, a carrier frequency of at least 1 in 100, a detrimental effect on the quality of life, potential of being diagnosed prenatally, and causing cognitive or physical impairment and need for surgical or medical intervention.
Johansen Taber K, Ben-Shachar R, Torres R, et al. A guidelines-consistent carrier screening panel that supports equity across diverse populations. Genet Med. 2021;24(1):201-213. doi:10.1016/j.gim.2021.09.009