3.3 Clinical implication of GS
Of the 23 cases with positive diagnoses, nine families experienced a change in clinical management and received information that impacted family planning. No changes to clinical care were noted in five families and clinical utility data was unavailable for six families.
Therapeutically, by knowing the molecular etiology of the patients, four families received potential targeted treatments. Patient iw138 in Family WGSI045XH was diagnosed with Pyruvate dehydrogenase E1-alpha deficiency (OMIM 312170). Her treatment was changed from levocarnitine to a ketogenic diet. Patient iw266 in Family WGSI086XH started methylene blue treatment after she was diagnosed by Methemoglobinemia (OMIM 250800) with compound heterozygous variants in CYB5R3 gene. For diseases with currently no known effective treatment options, GS helped to point out the possible therapies. Family WGSI010XH, diagnosed by a newly reported mitochondrial disorder caused by biallelic HPDLvariants(Sun et al., 2021), received “mito cocktail” treatment. Patient iw323 from Family WGSI104XH received omeprazole and acetylcysteine treatment by the local hospital as they found research on proton pump inhibitors as a potential therapy for NGLY1 deficiency [PMID: 28512024]. After receiving the molecular diagnosis, two families (WGSI028XH and WGSI058XH) stopped the unnecessary levocarnitine medicine.
Five families reported that GS diagnosis results altered their family planning. Three families (WGSI010XH, WGSI015XH and WGSI036HR) welcomed healthy children with the help of preimplantation diagnosis and prenatal diagnosis. Two families (WGSI058XH and WGSI095XH) reported they were planning for the next pregnancy.