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Source publication
Sitosterolemia is a rare atherogenic sterol storage disease with variability in its presentation requiring a high degree of clinical suspicion. We present 8 cases of sitosterolemia from an Amish kindred that, despite a background of decreased genetic and lifestyle variability, still had markedly variable presentations. (Level of Difficulty: Advance...
Citations
... HeFH does not predispose children to becoming overweight or obese, although unhealthy lifestyle choices may exacerbate LDL-C elevation and contribute to excessive weight gain. Physical manifestations, such as xanthoma, xanthelasma, and thickening of the Achilles' tendons, are extremely rare in children and, when present, should prompt investigation for other causes, such as homozygous familial hypercholesterolemia [46], sitosterolemia [47,48], and primary sclerosing cholangitis [49]. Family history can be helpful but is often incomplete, unreliable, or unavailable and fails to identify as many as 30-60% of youth with hypercholesterolemia [50]. ...
Purpose of Review
Familial hypercholesterolemia (FH), a common inherited disorder of LDL-C metabolism that predisposes to premature cardiovascular disease, is underdiagnosed. Despite recommendations for screening all children and initiation of lipid-lowering medication beginning at 8–10 years of age, adherence to guidelines is low. Most individuals with FH are inadequately treated, especially women and children. The purpose of this review is to discuss current literature and recommendations for the diagnosis and treatment of heterozygous FH (HeFH) in the pediatric population.
Recent Findings
Twenty-year outcome data demonstrate lower rates of atherosclerotic cardiovascular disease (ASCVD) related events and death in individuals with FH who were treated with statins from childhood, compared to those who initiated statins in adulthood. While diagnosis rates of FH are slowly improving, most clinicians do not adhere to recommendations for cholesterol screening in youth.
Summary
Identifying youth with FH offers the opportunity for early intervention to prevent ASCVD and identify affected relatives through reverse cascade screening.
Purpose of review
Newborn screening is one of the most successful public health programs of the last century and offers unparalleled access to universal screening for a variety of metabolic and other disorders. Interest in development of newborn screening for lipid disorders has intensified in recent years. Screening newborns for lipid disorders has important implications for the health of the newborn as well as their relatives, and in the case of more common lipid disorders like familial hypercholesterolemia, could have important public health implications.
Recent findings
Recent studies have demonstrated feasibility of measuring biomarkers for heterozygous familial hypercholesterolemia from newborn screening dried blood spot specimens. Another lipid disorder, cerebrotendinous xanthomatosis, is currently amenable to newborn screening utilizing currently available assays. New research in next-generation sequencing as a primary screen in newborns will also identify both common and rare lipid disorders in newborns.
Summary
Historically, newborn screening for lipid disorders was not done for many reasons, but new research has developed testing methods that may successfully identify common and rare lipid disorders. This will impact the health of the newborn but could also impact family members and public health.
Purpose of Review
The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels of plasma plant sterols. This sterol storage condition is caused by biallelic loss-of-function genetic variants in either ABCG5 or ABCG8, leading to increased intestinal absorption and decreased hepatic excretion of plant sterols. Clinically, patients with sitosterolemia usually exhibit xanthomatosis, high levels of plasma cholesterol, and premature atherosclerotic disease, but presentation can be highly heterogeneous. Therefore, recognition of this condition requires a high level of suspicion, with confirmation upon genetic diagnosis or through measurement of plasma phytosterols. Treatment of sitosterolemia with both a plant sterol-restricted diet and the intestinal cholesterol absorption inhibitor ezetimibe can reduce efficiently the levels of plasma plant sterols, consisting in the first-line therapy for this disease.
Recent Findings
Since hypercholesterolemia is often present in individuals with sitosterolemia, it is important to search for genetic variants in ABCG5 and ABCG8 in patients with clinical criteria for familial hypercholesterolemia (FH), but no variants in FH implicated genes. Indeed, recent studies have suggested that genetic variants in ABCG5/ABCG8 can mimic FH, and even when in heterozygosis, they may potentially exacerbate the phenotype of patients with severe dyslipidemia.
Summary
Sitosterolemia is a genetic lipid disorder characterized by increased circulating levels of plant sterols and clinically manifested by xanthomatosis, hematologic disorders, and early atherosclerosis. Awareness about this condition, a rare, but commonly underdiagnosed and yet treatable cause of premature atherosclerotic disease, is imperative.
