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Familial hypercholesterolemia (FH) is the most common and serious form of inherited hyperlipidaemia. Dominantly inherited with high penetrance, untreated FH leads to premature death from coronary artery disease due to accelerated atherosclerosis from birth. Despite its importance, there is still a major shortfall in awareness, detection and treatment of FH worldwide. International models of care for FH have recently been published, but their effective implementation requires the garnering of more knowledge about the condition. The "Ten Countries Study" aims to investigate diagnostic, epidemiological and service aspects, as well as physician practices and patient experiences of FH in several countries in the Asia-Pacific Region and the Southern Hemisphere. Five observational studies are being undertaken that will systematically investigate the following aspects of FH: the phenotypic predictors of low-density lipoprotein receptor mutations, the point prevalence in available community populations, current knowledge and clinical practices among primary care physicians, availability and utilisation of services and facilities, and patient perceptions and personal experiences of the condition. The information gathered will inform better clinical practice and will enable the development of country-specific models of care for FH.

A total of 86 unrelated Malaysian patients with familial hypercholesterolaemia (FH) were studied for mutations in their low-density lipoprotein receptor (LDL-R) gene. Amongst them, 23 had a LDL-R gene mutation, while none having an Apolipoprotein B-3500 (Apo B-3500) mutation. Patients with the LDL-R gene defect appeared to have a higher level of low-density lipoprotein cholesterol (LDL-C), an increased incidence of xanthomas and coronary heart disease (CHD), but no relationships were found between the type of LDL-R gene mutations and their lipid levels or clinical signs of CHD. In contrast to Western data, our findings seemed to indicate a predominance of mutations in the ligand binding domain and an absence of Apo B-3500 gene mutation. The latter finding may offer a genetic basis as to why Asian patients with familial hypercholesterolaemia have lower LDL-C levels and less premature CHD than their Western counterparts.

The aim of this study was to detect mutations in the genes coding for the low-density lipoprotein receptor and apolipoprotein B in patients of Southeast Asian origin with clinically diagnosed familial hypercholesterolemia (FH) and to relate these findings with the observed lower incidence of coronary heart disease in this part of the world. A total of 86 unrelated patients with FH were selected on clinical grounds, and complete DNA analysis of the low-density lipoprotein (LDL)-receptor and apolipoprotein B (apoB) genes by DGGE and DNA-sequencing was performed. In the majority (73%) of the cohort studied, no mutations could be detected, even after extensive analysis of the LDL-receptor and apoB genes. However, the 22 patients with a mutation had significantly more xanthomas and a higher incidence of coronary heart disease and levels of low-density lipoproteins were also significantly different. There was no correlation between the type of the mutation and lipoprotein levels or clinical signs of atherosclerosis. The fact that the majority of the FH patients studied had no detectable mutation and that this group had a significant milder phenotype, suggests the presence of a third gene in the Southeast Asian population, predominantly leading to a disorder resembling a milder form of FH. A similar, but less frequent, trait has recently been described in a number of European families.

This paper highlights two cases of paediatric familial hyperlipidaemia (hypercholesterolaemia and hypertriglyceridaemia). The first case was an 11 year old Chinese boy, a "homozygous" (Type II) hypercholesterolaemic patient. He had extremely high blood cholesterol level (19.4 mmol/l), severe multiple xanthoma and abnormal resting electrocardiogram. He had repeated heart attacks and died at the age of 15 in spite of early intervention, treatment and follow up. The second case was a 2 1/2 years old girl who had severe hypertriglyceridaemia. She had raised cholesterol (6.2 mmol/l) and extremely high triglycerides (14.8 mmol/l). The patient did not resemble Type I lipoproteinaemia which is classically seen in childhood. On the contrary, the patient exhibited clinical and biochemical manifestations of a Type V lipoproteinaemia which often occurs in adults. Apart from a Type V lipoprotein pattern, the patient had low post hepatic lipase activity (PHLA), Apo C II and Apo E2/E3 phenotype. In addition, the lipid profile of her family members (both the parents and brothers) had raised triglycerides and thus ruled out the Type I lipoprotein inheritance pattern, which is an autosomal recessive condition. The issue of paediatric hyperlipidaemia, their management and treatments are discussed.