The Spectrum of Familial Hypercholesterolemia (FH) in Saudi Arabia: Prime Time for Patient FH Registry

Abstract

Background:Familial hypercholesterolemia (FH) is a life-threatening inherited condition. Untreated patients have the risk to develop raised plasma levels of cholesterol, atherosclerosis and cardiovascular disease (CVD). If diagnosed and treated early in life, the pathological consequences due to atherosclerosis could be avoided and patients with FH can have an anticipated normal life. Mounting evidence suggests that FH is underdiagnosed and undertreated in all populations. The underlying molecular basis of FH is the presence of mutations in one or more genes in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) or proprotein convertase subtilisin/kexin 9 (PCSK9). However, their prevalence is largely unknown in Saudi Arabia but given the high rates of consanguinity, the prevalence appears to be higher. Furthermore, the high prevalence of obesity and diabetes mellitus in Saudi Arabia increases the vascular disease burden in FH cases by adding additional CVD risk factors.Objective:This article explores the spectrum of FH-causing mutations in the highly consanguineous Saudi community, the need for establishing the Saudi FH registry, the challenges in creating gene databases, and cascade screening.Conclusion:The establishment of FH registry and genetic testing should raise awareness not only among healthcare professionals, but the general population as well. It also helps to provide the best treatment regimen in a cost effective manner to this under-recognised population of FH patients.

Assessment of physicians’ awareness and knowledge of familial hypercholesterolemia in Saudi Arabia: Is there a gap?

“…A strong pre-registry campaign (e.g. in the media) can achieve these objectives, and could identify any cultural barriers hindering the establishment of a registry [ 36 ]. Also, the results of this registry can be fed back to physicians in the form of publications, audits, and conferences to engender a more personalized approach to improving patient care.…”

“…FH registry can help in determining the genetic predisposition of such condition which would help in providing an early intervention. Also, it will enable identifying the most common disease-causing mutations among the Saudi population and identify population specific novel mutations helping in future rapid molecular diagnosis [ 36 ]. The researchers can access de-identified data of FH database through research ethics committees or the consultative body to determine the burden of disease, and health outcomes.…”

“…The researchers can access de-identified data of FH database through research ethics committees or the consultative body to determine the burden of disease, and health outcomes. In addition, the careful documentation of FH cases can provide statically improved studies, meta-analytical studies, scientific collaborations, and international clinical trials to take place in Saudi Arabia [ 36 ]. Further studies on the natural history of the disease within the Saudi population can be conducted based on the results of this registry; subsequently, this would provide strategic evidence for therapies and suggest methods for economic improvement in healthcare.…”

“…Further studies on the natural history of the disease within the Saudi population can be conducted based on the results of this registry; subsequently, this would provide strategic evidence for therapies and suggest methods for economic improvement in healthcare. Furthermore, a comprehensive FH database will support and justify universal screening of FH in children (ages 2–9 years) in Saudi Arabia as has been implemented in other countries [ 36 ].…”

Whole Exome Sequencing Reveals Multiple Mutations in Uncommon Genes of Familial Hypercholesterolaemia

“…7 In Saudi Arabia, there are inadequate numbers of reports available for prevalence and molecular characteristics of FH. 4,[8][9][10][11][12][13][14][15] The disease may have a higher prevalence in Saudi Arabia than in other neighboring countries because consanguineous marriages exceeding 55% 16,17 and due to the lack of national registries and genetic screening programmes for FH, the disease is under diagnosed and under estimated. In the present study, we performed WES of FH patient, shown to be negative for LDLR mutation.…”