“Cascade Screening” is an effective method of locating ADH carriers: it makes use of genealogy and tracks down and tests relatives of known cases. Since FH is a genetically inherited disease the advantages here should be obvious, and as expected, the molecular hit-rate is high. However, this efficiency is not attractive to the pharmaceutical industry, even if systemically possible, because the majority of carriers have milder consequences of the mutations than previously thought, as we see in the authors’ own data. It is no surprise then that industry-funded authors prefer clinical screening. Here is the concluding sentence to the 2nd report: “One must treat the phenotype not the genotype, and LDL-cholesterol should be lowered as early as possible to recommended levels regardless of information on mutation.” Again, FH is a genetically inherited disease and to prefer the phenotypic appearance of a disease to the genotypic print of that diseaseis the same as having a detective prefer circumstantial evidence when a forensic chain of facts is available.
Here is a summary of Cascade Screening in the United States: “There are currently no systematic approaches to the identification of FH patients or to cascade screening of their relatives in the United States. In addition, our health care system lacks key structural elements to facilitate the collection of national longitudinal data to measure and track the clinical progress of diagnosed patients.” ~ Am Heart J. 2014 December; 168(6): 807–811. doi:10.1016/j.ahj.2014.09.001., “Reducing the burden of disease and death from familial hypercholesterolemia: A call to action” — Joshua W. Knowles, et al.
“Ms. Sturm observed that it has been shown, based on data from other countries, that FH cascade screening – systematic family tracing – can be cost effective, and further, that cascade screening that combines genetic testing plus lipid testing is more cost-effective than a lipid panel alone. However, she said, while detection of pathogenic LDLR, APOB, or PCSK9 provides an unequivocal diagnosis of FH, such genetic testing has not been systematically incorporated in the US, and there are no US guidelines recommending genetic testing in FH. In the US, therefore, genetic testing is not the standard of care, even though it is considered the diagnostic gold standard. Ms. Sturm noted that in the US, clinical genetic testing is available via multiple commercial laboratories, but these vary in clinical sensitivity, cost, and health insurance billable allowances. Physicians who want genetic testing to confirm index cases and screen family members are often deterred by the knowledge that a genetic test for FH can be ordered but not necessarily reimbursed. In addition, cardiologists and other clinicians may be confused about when to order a genetic test.” ~ Amy Sturm MS, CGC (Clinical Associate Professor and Certified Genetic Counselor, Division of Human Genetics; Associate Professor, Internal Medicine; Ohio State University), Proceedings of the FH Foundation’s inaugural Familial Hypercholesterolemia Summit: Awareness to Action Annapolis, Maryland — September 18th & 19th, 2013