• cholesterol
• diagnosis
• hyperlipidemias
• lipids
• lipoproteins

Sulaiman presents a best practice review for primary/monogenic dyslipidaemia, their clinical presentation and best use of molecular genetics for earlier diagnosis.1 This review is important in the context of such patients, with multisystem issues, presenting to non-lipidology specialties to enable more timely diagnosis of dyslipidaemia-associated inherited metabolic disease (IMD). Efficient diagnosis ensures appropriate medical management (particularly important where disease-specific medications exist) and attenuates long-term sequelae.

Clinical guidelines, and best practice reviews such as this, are often not followed.2 3 There may be a significant delay from clinical presentation to diagnosis of such IMDs. This is due to the diversity of symptoms and the breath of specialties to which such patients present, most notably and often in the first instance Primary Care. Patients may be asymptomatic with the incidental finding of abnormal lipids the only prompt for further investigation. Patients with non-specific or variable symptoms may progress down a winding road of referrals and inappropriate investigation, which can take years. Even patients with classical signs of primary dyslipidaemia, for example, eruptive or tuberous xanthoma and premature cardiovascular disease, will take time to be investigated and thus diagnosed in the absence of specialist knowledge or availability of multigene panel testing for monogenic dyslipidaemic mutations.

As suggested by the author, such a tool (a multigene panel) would expedite diagnosis for some of these rarer diseases.1 The diagnostic yield of these dyslipidaemia next-generation sequencing panels will depend on a range of factors, such as pretest probability, the number of disorders and genes represented in the panel, analytical performance, such as coverage metrics, detection of non-coding and regulatory variants, availability of deletion/duplication (copy number variant) analysis in conjunction with sequencing and clinical interpretation of the findings.

Clinical Chemistry laboratories producing test results are well positioned to proactively direct and advise the non-lipidologist …