Table 1
HoFH satisfies conditions for screening.
| SCREENING CRITERIA | EVIDENCE |
|---|---|
| HoFH is an important public health problem |
|
| HoFH natural history is well understood |
|
| There is a suitable, acceptable diagnostic test |
|
| Treatment recommendations and acceptable treatments exist |
|
| Facilities for diagnosis and treatment exist |
|
| Cost is acceptable to society |
|
Table 2
Risk-Benefit considerations of incorporating HoFH into newborn screening [33].
| POTENTIAL BENEFITS | POTENTIAL RISKS |
|---|---|
| Would increase identification of a condition that causes premature CVD, facilitating early treatment | Evaluation and care plan for phenotype positive/gene negative patients not established |
| HoFH treatment is highly beneficial | There is little data on HoFH treatment prior to 5 years of age; side effects of most treatments in infancy are unknown. |
| Identifying HoFH in an infant allows relatives to be screened, improving the health of family members | Screening children to benefit family members shifts emphasis away from health interests of the child alone [34]. |
| Adding HoFH to NBS could simultaneously incorporate screening for severe HeFH | Patients with milder forms of HeFH would not be identified unless genetic screening performed. |
| Adding HoFH to NBS does not require an additional blood sample, since NBS is already done at birth | |
| Assays for testing HoFH on the NBS are already available and reagents are low cost | Proposed screening methods not fully validated; full downstream costs of screening and diagnosis are not known. |
Table 3
Select disorders screenable in the newborn period and their estimated prevalence.
| DISORDER | ESTIMATED PREVALENCE IN US POPULATION |
|---|---|
| Heterozygous familial hypercholesterolemia | 1 in 300 |
| Phenylketonuria* | 1 in 16,200 |
| Maple Syrup Urine Disease* | 1 in 150,000 |
| Homozygous familial hypercholesterolemia (high prevalence estimate) | 1 in 160,000 |
| Homozygous familial hypercholesterolemia (low prevalence estimate) | 1 in 400,000 |
| Glutaric Acidemia Type 2* | 1 in 465,000 |
| Carnitine Palmitoyltransferase Deficiency Type 1A* | 1 in 500,000 |
[i] *Disorder currently listed on the Recommended Uniform Screening Panel. This is the list of disorders that the Secretary of the Department of Health and Human Services recommends states screen for as a part of their standard universal newborn screening programs. (https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp).
Figure 1
Opportunities to identify HoFH over the life course.
Table 4
Facilitating HoFH care.
| MEASURES | RATIONALE |
|---|---|
| Provide education to family medicine physicians, pediatricians, internists, obstetricians, nurse practitioners and physician assistants regarding the value of screening for HoFH in proper settings and recognition of physical findings | Both HeFH and HoFH are under-diagnosed and under-treated. |
| Guarantee health care coverage for all HoFH patients | HoFH is a rare disease with high lifetime cost for life-saving health care. |
| Create a separate diagnostic code for HoFH | Allows tracking of those with the condition. |
| Establish referral networks nationwide for HoFH care that include shared care between home facilities and specialized care sites | Will improve delivery of evidence-based health care nationally; facilitates the development of a HoFH registry and research. |
| Educate the public about the value of 1) Lipid testing to identify actionable LDL-C levels and to improve cardiovascular health and 2) Genetic testing for Tier 1 conditions, including FH, to improve acceptability; remove discriminatory barriers in society to such testing | Overcome barriers to the public’s understanding of FH as a condition and the understanding that lipid control is important for long term health. |