Universal Familial Hypercholesterolemia Screening in Children

Study Overview
=================
Brief Summary
-----------------
30 million individuals globally with undiagnosed familial hypercholesterolemia (FH) are at a substantial cardiovascular disease (CVD) risk, which could be normalized by early diagnosis and treatment. Effective screening strategies are urgently needed, but the data on universal FH screening (uFHs) is scarce. The investigators aim to assess the overall performance of the uFHs program in Slovenia and to compare the common elements to the pilot uFHs program in Lower Saxony (LS; Germany).

Detailed Description
-----------------
The study will include pediatric patients (or their siblings and parents in Slovenian cohort) undergoing the universal hypercholesterolemia screening; those with elevated cholesterol at universal cholesterol screening at primary care level are referred to the lipidology specialist at the UMC Ljubljana (Slovenia) or Kinderkrankenhaus auf der Bult (Lower Saxony, Germany). For those with elevated cholesterol levels, the familial hypercholesterolemia genetic diagnostics is done centrally in UMC Ljubljana. Only those will be included from whom a signed informed consent by themselves or by their parents/guardians will be obtained prior to the genetic diagnosis of familial hypercholesterolemia.

Official Title
-----------------
Universal Screening for Familial Hypercholesterolemia in Children - a Practical Approach

Conditions
-----------------
Familial Hypercholesterolemia, Polygenic Hypercholesterolaemia

Intervention / Treatment
-----------------
* Diagnostic Test: Genetic analysis
* Diagnostic Test: Lipid levels measurement


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Elevated total cholesterol (cohort 1) or LDL-cholesterol (cohort 2) at universal screening program in children. Completed FH genetic analysis (cohort 3). Parent or sibling of child with confirmed familial hypercholesterolemia (cohort 4). Exclusion Criteria: Children with hypercholesterolemia not referred through the screening program. FH genetic analysis not completed.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children with hypercholesterolemia (Slovenia)<br>Children (aged 5 years) with total cholesterol measurement at primary care pediatricians at the programed visit prior to school entry. | Diagnostic Test: Lipid levels measurement<br>* Measurements of lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, TG) using standard methods.<br>|
| Children with hypercholesterolemia (Lower Saxony, Germany)<br>Children (aged 2-6 years) with LDL-cholesterol measurement during the compulsory routine check-ups and at any voluntary visits to the primary care pediatricians. | Diagnostic Test: Lipid levels measurement<br>* Measurements of lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, TG) using standard methods.<br>|
| Children referred for FH genetic analysis (Slovenia and LS)<br>Children referred for familial hypercholesterolemia genetic analysis to the tertiary center, according to the screening algorithm. | Diagnostic Test: Genetic analysis<br>* After obtaining written consent from patients, DNA is isolated, and genetic analysis of the know familial hypercholesterolemia disease-causing genes (LDLR, APOB, PCSK9) is performed.<br>Diagnostic Test: Lipid levels measurement<br>* Measurements of lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, TG) using standard methods.<br>|
| Parents and siblings of children with confirmed FH (Slovenia)<br>Parents or siblings of index cases with completed familial hypercholesterolemia genetic analysis, according to the screening algorithm. | Diagnostic Test: Genetic analysis<br>* After obtaining written consent from patients, DNA is isolated, and genetic analysis of the know familial hypercholesterolemia disease-causing genes (LDLR, APOB, PCSK9) is performed.<br>Diagnostic Test: Lipid levels measurement<br>* Measurements of lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, TG) using standard methods.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of universal familial hypercholesterolemia screening | The investigators aim to assess the overall performance (number of cases per 1000/screened; rate of implementation) of the universal screening for familial hypercholesterolemia. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genotype-phenotype correlations in children with familial hypercholesterolemia | The investigators will assess the phenotypic characteristics in relation to genotypes; specificity and sensitivity of genetic analyses will be determined. | 36 months | 
| Prevalences of heterozygous and homozygous familial hypercholesterolemia | Number of genetically confirmed cases are compared to the number of live-born children in same period. | 36 months | 
| Cost-effectiveness analysis of universal screening for familial hypercholesterolemia | The costs per new genetically confirmed case are estimated considering the costs for all the three steps of the screening algorithm. | 36 months | 
| Comparison of universal and pilot familial hypercholesterolemia screening | The investigators aim to compare the common elements of the pilot universal hypercholesterolemia program in Lower Saxony (LS; Germany) to the Slovenian national universal familial hypercholesterolemia screening. | 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cascade, familial hypercholesterolemia, FH, screening, universal, pediatric