[MIM 143 890, 144 010, 602 247, 603 776, 603 813]

Dyslipidemia with elevated levels of LDL due to a defect of endocytosis of LDL.

Codominant transmission of genes mutations of

-        the LDLR gene (19p13.2) coding for the LDL receptor; occurs with or  without hypertriglyceridemia

-        the APOB gene (2p24) coding for apolipoprotein B100 (type B)

-        or the PCSK9 gene coding for a proprotein convertase involved in degradation of the lipoprotein receptor responsible for elimination of excess LDL-C

Two clinical forms are described:

-        heterozygous form: 1: 500; usually discovered during a lipid check-up, in the presence of coronary artery disease or of extravascular deposits (xanthomas, corneal arcus)

-        homozygous: 1/106 ; presence, in a child under 2 years of age,  of extravascular deposits of cholesterol (cutaneous or tendinous xanthomas) and of an arteriopathy (coronary artery disease, acquired aortic stenosis) before the age of 10 years.

A third clinical form (recessive transmission of a mutation of the  LDL RAP1 and ABCG5/ANCG8 genes) is very rare: xanthomas and early atherosclerosis, severe hypercholesterolemia, but parents are normolipidemic.

Treatment:

-        heterozygous form: low fat diet, statins (if > 8 years), inhibitor of intestinal absorption of cholesterol or resins (cholestyramine if < 8 years, with vitamin D supplements); in case of resistance to those treatments: aliracumab orally (monoclonal antibody inhibiting the proproteinconvertase PCSK9)

-        homozygous recessive forms: diet is not effective; treatment by apheresis on beads of polyacrylamide (DALI®) or liver transplantation (to be completed before the occurrence of cardiovascular sequelae) .

Secondary hypercholesterolemia, unrelated to any genetic abnormality, can be observed in case of: obesity, hypothyroidism, glycogen storage disease, chronic cholestasis, nephrotic syndrome, steroid treatment, anorexia nervosa, oral contraception

Anesthetic implications: 

early atheromatosis with hypertension; full cardiac assessment in case of xanthomas; in case of coronary lesions, management similar to an adult coronary patient. Avoid using a prolonged infusion of propofol in case of hypertriglyceridemia.

References : 

• Girardet J-P. 
  Prise en charge des hypercholestérolémies de l’enfant. 
  Arch Pédiatr 2006 ; 13 : 104-10.
• Lefort B, Giraud C, Saulnier J-P, Bott L, Gambert C, Sosner P, Hankard R. 
  Traitement d’une hypercholestérolémie familiale homozygote par LDL-aphérèse chez un enfant de 4 ans.
  Arch Pédiatr 2009 ; 16 : 1554-8.

Updated: February 2024