Homozygous familial hypercholesterolaemia (HoFH) is the most severe form of FH and usually presents in childhood. It is rare, affecting about 1:300,000 people and occurs when a person inherits 2 faulty copies of the LDL receptor gene (or sometimes other genes which cause FH), one from each parent. As a result, the LDL cholesterol (LDL-C) levels accumulate to very high levels from birth, increasing the risk of life-threatening cardiovascular problems during childhood and early adulthood.

HoFH should be suspected in any child with external signs of high cholesterol eg corneal arcus  (a grey-white ring in the eye), or xanthomas (fatty deposits in the skin). However not all children have external signs and if HoFH is not detected and treated, the dangerously high LDL-C levels accumulate in the blood vessels and on the heart valves placing the young person at risk of heart attacks or strokes. The diagnosis is made by extremely high LDL-C levels (over 13 mmol/L) and/or genetic testing.

Treatment involves aggressive lipid lowering therapies as soon as the diagnosis is made. High dose statin therapy together with ezetimibe may not be enough to bring LDL-C to safer levels and lipid apheresis (filtering LDL-C from the blood) every 1-2 weeks lifelong is usually required. Rarely liver transplant to replace the defective LDL receptors is needed. Recently, PCSK-9 inhibitors and new therapies in clinical trials have been shown to be effective and are likely to change the course of this devastating diagnosis.