Identification and Treatment of Patients with Homozygous Familial Hypercholesterolaemia: Information and Recommendations from a Middle East Advisory Panel

Abstract

We present clinical practice guidelines for the diagnosis and treatment of homozygous familial hypercholesterolaemia (HoFH) in the Middle East region. While guidelines are broadly applicable in Europe, in the Middle East we experience a range of confounding factors that complicate disease management to a point whereby the European guidance cannot be applied without significant modification. Specifically, for disease prevalence, the Middle East region has an established epidemic of diabetes and metabolic syndrome that can complicate treatment and mask a clinical diagnosis of HoFH. We have also a high incidence of consanguineous marriages, which increase the risk of transmission of recessive and homozygous genetic disorders. This risk is further augmented in autosomal dominant disorders such as familial hypercholesterolaemia (FH), in which a range of defective genes can be transmitted, all of which contribute to the phenotypic expression of the disease. In terms of treatment, we do not have access to lipoprotein apheresis on the same scale as in Europe, and there remains a significant reliance on statins, ezetimibe and the older plasma exchange methods. Additionally, we do not have widespread access to anti-apolipoprotein B therapies and microsomal transfer protein inhibitors. In order to adapt existing global guidance documents on HoFH to the Middle East region, we convened a panel of experts from Oman, Saudi Arabia, UAE, Iran and Bahrain to draft a regional guidance document for HoFH. We also included selected experts from outside the region. This panel statement will form the foundation of a detailed appraisal of the current FH management in the Middle Eastern population and thereby provide a suitable set of guidelines tailored for the region.

The Genetic Spectrum of Familial Hypercholesterolemia (FH) in the Iranian Population

“…Historically, a patient was clinically diagnosed with HoFH, if he/she had untreated LDL-C > 13 mmol/L (500 mg/dL) or treated LDL-C > 8 mmol/L (300 mg/dL), and the presence of TXs before the age of 10 years, or the patient’s parents were diagnosed with HeFH 22 . However, the range of LDL-C levels reported in HoFH patients is broad and can overlap with ranges found in other types of FH 15,22 , which is another challenge for identification. Two cases of Iranian children with HoFH have reported severe septum and complex CHD outcomes 23,24 .…”

“…In 2015, clinical practice guidelines for the diagnosis and treatment of HoFH in the Middle East region was published, which showed several factors such as consanguineous marriages, treatment accessibility and cascade screening limitations that were not found in Western countries 15 . Previous Iranian FH Genetic studies have used limited genetic screening methods based on PCR technology 16–20 .…”

Consensus clinical recommendations for the management of plasma lipid disorders in the Middle East

“…Elevated LDL-C in FH is present from birth and there is evidence that the prognosis of both heterozygous and homozygous FH is improved with early treatment [4]. Detection of FH via clinical assessment alone can be particularly challenging in patients where LDL-C elevation is less marked [29] and the CVD risk levels of patients with FH may not accurately be predicted by the use of multivariate risk scoring (see Section 3) [4]. Therefore, genetic screening should be considered to identify common mutations causing FH in the region for new-borns with LDL-C elevation or clinical signs suggestive of FH.…”

“…A systematic literature review identified 57 mutations in the Middle East and North Africa [30]; Table 1 summarises those reported in Middle Eastern countries. To date, the availability and uptake of genetic testing for FH in the Middle East has been limited [29].…”

“…A number of patient groups should automatically be considered to be at high or very high risk of developing ASCVD, and should receive pharmacological therapy targeting plasma lipids. These include patients with known ASCVD [2,4,21,22], FH (due to a high risk of premature ASCVD, in absence of other risk factors) [4,21,29], T2DM [2,4,21,22] and CKD [2,4,21,22]. For other patients outside of these high-risk groups, the patient's global risk of ASCVD should be estimated using a scoring system (see Section 3.2) [4].…”