Familial homozygous hypercholesterolemia: When to turn to transplant?

Asai, Akihiro; Kohli, Rohit

doi:10.1111/petr.12561

Cited by 4 publications

(1 citation statement)

References 20 publications

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“…However, it may be more prevalent in other places. A series of 36 cases in Iran [104], where apheresis is not widely available has recently been published and there are several recent case descriptions of successful outcome [105e107]. The genetic and clinical heterogeneity of HoFH is now recognized and should determine the clinical management.…”

Section: Treatment Of Children With Hofh and Licensing Of New Drugsmentioning

confidence: 98%

HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom

et al. 2016

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This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK.

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Section: Treatment Of Children With Hofh and Licensing Of New Drugsmentioning

confidence: 98%

HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom

et al. 2016

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Tendons Involvement in Congenital Metabolic Disorders

Abate

Salini

Andı́a

2016

Advances in Experimental Medicine and Biology

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Congenital metabolic disorders are consequence of defects involving single genes that code for enzymes. Blocking metabolic pathways, the defect leads to the shortage of essential compounds, and/or to the accumulation of huge quantities of precursors, which interfere with normal functions. Only few of these diseases are characterized by a clinically significant tendon involvement.Heterozygous Familial Hypercholesterolaemia results from the inheritance of a mutant low-density lipoprotein receptor gene; patients show high cholesterol levels, precocious coronary artery disease, and may develop tendon xanthomata (mainly in Achilles tendon). The detection of xanthomata is important, because it allows an early diagnosis and treatment of the disorder. Cerebrotendinous Xanthomatosis is a rare genetic metabolic disorder of cholesterol and bile acid metabolism, characterized by accumulation of cholestanol in brain and tendons. Tendon abnormalities are similar to those reported in Heterozygous Familial Hypercholesterolaemia. Alkaptonuria is caused by a deficiency of the enzyme homogentisic acid oxidase. Due to the accumulation of the homogentisic acid, tendons and ligaments are characterized by a typical ochre/yellow pigmentation (ochronosis), with ensuing inflammation, calcification and rupture. In Congenital Hypergalactosemia an increased tendon collagen cross-linking by non-enzymatic galactosylation can be observed. Finally, Congenital Hypophosphatasia may be associated to deposition of hydroxyapatite crystals in rotator cuff, elbow, and Achilles tendons.

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Homozygous familial hypercholesterolaemia: update on management

France

2016

Paediatrics and International Child Health

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Homozygous familial hypercholesterolaemia (HoFH) is an inherited disease causing an approximately fourfold increase in blood low-density lipoprotein cholesterol (LDLC) from birth compared with the age-matched normal population owing to reduced low-density lipoprotein receptor (LDLR) activity. Such elevated cholesterol is associated with accelerated atheromatous disease, particularly of the aortic root and coronary arteries. However, HoFH is clinically heterogeneous, reflecting residual low-density lipoprotein receptor (LDLR) activity. The main objective in treating children may be stated to be the avoidance of irreversible cardiac damage requiring heart transplantation by sufficient lowering of blood cholesterol. Lipoprotein apheresis or plasmapheresis are safe means of lowering cholesterol but may be insufficient on their own. Statin drugs, PCSK9 inhibitors ezetimibe and bile acid sequestrants are relatively ineffective if LDLR activity is lacking, but should be used if effective. Two new drugs, lomitapide and mipomersen, have been licensed specifically for HoFH by some regulatory authorities. They work by reducing LDL production rate. They have been associated with fatty liver in adults. Evidence of safety in children is lacking. An alternative is liver transplantation, which replaces the missing LDLR and normalises cholesterol. Clinicians are faced with a dilemma in choosing between these options or deferring such treatment associated with potential harm. Individual case descriptions are an important means of informing clinical judgement. Management of the two cases described in this issue is discussed in the light of modern developments in transplantation and pharmacotherapy.

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Familial homozygous hypercholesterolemia: When to turn to transplant?

Cited by 4 publications

References 20 publications

HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom

HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom

Tendons Involvement in Congenital Metabolic Disorders

Homozygous familial hypercholesterolaemia: update on management

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