|30 kb deletion testing||Known pathogenic mutation, common in IKD patients||Low complexity, rapid assay. When found homozygous indicates IKD.||Rare mutation, whose presence is more likely to indicate carrier status (i.e. “false positive”) and where the absence will still not avoid possible IKD (“false negative”)|
|Psychosine testing||Appears to be associated with active disease in KD patients||Rapid test that when elevated indicates IKD.||Requires MS/MS equipment with higher sensitivity than that typically used in NBS labs but testing can be regionalized while still ensuring rapid turnaround time.|
|GALC Genotyping||With 30kbDel, it is traditionally considered the “gold standard” 2nd tier testing in KD-NBS, but there may still be GALC deletions missed, leading to false negative results.||Can identify those infants at highest risk for IKD. Provides some reassurance to those who are carriers, have only enzyme lowering polymorphisms, or known “mild” mutations.||
Instrumentation and expertise required are beyond the capabilities of most NBS labs.|
Many GALC mutations identified through KD-NBS are of uncertain clinical significance. Database of all known KD genotypes not available to support genotype interpretations.