Case conference concerning 9-year-old boy having 20 mmol/lcholesterol: from diagnosis to effective treatment

Familial hypercholesterolemia (FHC) is the most common and most severe form of monogenic dyslipidemia with early and rapidly progressing atherosclerosis and its complications [1--4, 12, 14]. Without treatment, the prognosis for patients with FHC is as heavy as for AIDS patients. For the first time the molecular defect - absence or dysfunction of the LDL receptor (LDL-R), the main route for cholesterol catabolism in humans [2, 3, 12, 13] - was described with regard to this genetic disease. The article analyzes a clinical case of the disease in a 9-year-old boy.

семейная гиперхолестеринемия, моногенная дислипидемия, наследование, холестерин, липопротеиды низкой плотности, familial hypercholesterolemia, monogenic dyslipidemia, inheritance, cholesterol, low density lipoprotein

1. Rader D, Cohen J, Hobbs H. Monogenic hypercholesterolaemia: new insights in pathogenesis and treatment. J Clin Invest, 2003, 111: 1795-1803.

2. Descamps OS, Tenoutasse S, Stephenne X, Gies I, Beauloye V, Lebrethon MC, De Beaufort C, De Waele K, Scheen A, Rietzschel E, Mangano A, Panier JP, Ducobu J, Langlois M, Balligand JL, Legat P, Blaton V, Muls E, Van Gaal L, Sokal E, Rooman R, Carpentier Y, De Backer G, Heller FR. Management of familial hypercholesterolemia in children and young adults: consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization. Atherosclerosis, 2011, 218 (2): 272-80.

3. Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, Daniels SR, Gidding SS, de Ferranti SD, Ito MK, McGowan MP, Moriarty PM, Cromwell WC, Ross JL, Ziajka PE; National Lipid Association Expert Panel on Familial Hypercholes-terolemia. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia.J Clin Lipidol, 2011, 5 (3): S1-8.

4. Кухарчук В.В., Малышев П.П., Мешков А.Н. Семейная гиперхолестеринемия: современные аспекты диагностики, профилактики и терапии. Кардиология, 2009, 1: 76-83.

5. Heller DA, de Faire U, Pedersen NL, Dahlen G, and McClearn GE. Genetic and environmental influences on serum lipid levels in twins. N. Engl. J. Med, 328: 1150-1156.

6. Goldstein J, Hobbs H, and Brown M. Familial hypercholesterolemia. In The metabolic and molecular bases of inherited disease. C. Scriver, A. Beaudet, W. Sly, and D. Valle, editors. McGraw-Hill. New York, New York, USA, 2001. 2863-2913.

7. Sun XM et al. 1994. Familial hypercholesterolemia in China. Identification of mutations in the LDL-receptor gene that result in a receptor-negative phenotype. Arterioscler. Thromb., 14: 85-94.

8. Catapano A, Reiner Z, De Backer G et al. EAS/EAS Guidelines for the management of dyslipidemias. The Task Force for the management of dyslipideamias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis, 2011, 217S: S1-S44.

9. Thompson GR LDL apheresis. Atheroslerosis, 2003, 167: 1-13.

10. Khachadurian AK, Uthman SM. Experiences with the homozygous cases of familial hypercholesterolemia. A report of 52 patients. Nutr Metab., 1973, 15: 132-140

11. Bhattacharyya A.K, Connor W.E. Beta-sitosterolaemia and xanthomatosis. A newly described lipid storage disease in two sisters. J. Clin. Invest, 1974, 53: 1033-1043.

12. Nordestgaard BG, Chapman MJ, Humphries SE et al. Familial hypercholesterolaemia is underdiagnosed and untreated in general population:guidance for vlimicians to prevent coronary heart disease. Consensus Statement of the European Atherosclerosis Society. European HeartJournal, 2013.

13. Garcia CK et al. Autosomal recessive hypercholesterolaemia caused by Mutations in a putative LDL receptor adaptor protein. Science, 2001, 292: 1394-1398.

14. Watts GF, Gidding S, Wierzbicki AS, Toth PP, Alonso R, Brown WV, Bruckert E, Defesche J, Lin KK, Livingston M, Mata P, Parhofer KG, Raal FJ, Santos RD, Sijbrands EJ, Simpson WG, Sullivan DR, Susekov AV, Tomlinson B, Wiegman A, Yamashita S, Kastelein JJ. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. IntJ Cardiol., 2014, 171 (3) : 309-25.

15. Lee P, Hegele RA. Current Phase II proprotein convertase subtilisin/kexin 9 inhibitor therapies for dyslipidemia. Expert Opin Invest Drugs, 2013.

16. Mombelli G, Pavanello C et al. Novel therapeutic strategies for the homozygous familial hypercholesterolemia. Recent Pat Cardiovasc Drug Siscovery, 2013, 8 (2): 143-50.