Impacto da mutação C681X no tratamento de hipercolesterolemia familiar homozigótica: um relato de caso
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Apr 15, 2023
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Resumo
Objetivo: Relatar o impacto da mutação C681X no tratamento de hipercolesterolemia familiar homozigótica. Detalhamento do caso: Paciente, sexo masculino, 17 anos, com história de colesterol alto (LDL-c: 760 mg/dl), xantomas tuberosos e arcos corneanos desde os sete anos. Teste genético confirmou mutação homozigótica da C681X no receptor de LDL, sem alterações cardiovasculares. Pai, mãe, irmão apresentaram hipercolesterolemia com LDL-c >190mg/dl. Avó e tio maternos faleceram de infarto agudo do miocárdio antes dos 50 anos. Iniciou tratamento com Atorvastatina 40mg/dia e Ezetimibe 10mg/dia. Posteriormente, foi alterado Atorvastatina pela Rosuvastatina 40 mg/dia. Aos 11 anos, iniciou terapia tripla com Mipomersen 200mg, apresentou resposta adequada após 1 ano. O medicamento foi suspenso devido baixa segurança para sua idade, vindo elevar os níveis de LDL-c. Aos 13 anos utilizou Evolocumab (inibidor da PCSK9), na posologia de 140mg, associado a Rosuvastatina e a Ezetimibe. Depois de um ano, em terapia tripla, os resultados foram CT: 561 mg/dL;HDL-c: 27 mg/dL; LDL-c: 512 mg/dL; e TG: 110 mg/dL. Considerações finais: Paciente retornou após 3 anos sem ir às consultas, em uso de Atorvastatina 40mg/dia, Ezetimibe 10mg/dia e Evolocumab 140mg a cada 15 dias, sem controle adequado. Foi realizado ajuste da medicação e encaminhado paraseguimento multiprofissional.
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Como Citar
FadulS. S., ValenteA. A. M. O., LimaF. M., & PimentelL. dos S. (2023). Impacto da mutação C681X no tratamento de hipercolesterolemia familiar homozigótica: um relato de caso. Revista Eletrônica Acervo Saúde, 23(4), e11904. https://doi.org/10.25248/reas.e11904.2023
Seção
Estudos de Caso
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Referências
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21. KHACHADURIAN AK. The Inheritance of Essential Familial Hypercholesterolemia. The American journal of medicine, 1964; 37: 402–407.
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25. MILLAR JS, et al. Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production. Arteriosclerosis, thrombosis, and vascular biology, 2005; 25(3): 560–565.
26. MOLFETTA GA, et al. Mutational screening in the LDLR gene among patients presenting familial hypercholesterolemia in the Southeast of Brazil. Genetics and molecular research: GMR, 2017; 16(3): 1 0.4238/gmr16039226.
27. NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE (NICE). Familial hypercholesterolaemia: identification and management. London: NICE, 2019 Oct. (NICE Clinical Guidelines, No. 71).
28. NOHARA A, et al. Homozygous Familial Hypercholesterolemia. J Atheroscler Thromb., 2021; 28(7): 665-678.
29. PEREIRA AC, et al. I Diretriz Brasileira de Hipercolesterolemia Familiar (HF). Arquivos Brasileiros de Cardiologia, 2012; 99(2 suppl 2): 1–28.
30. RAAL FJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet, 2015; 385(9965): 341–350.
31. RAAL FJ, et al. Pediatric experience with mipomersen as adjunctive therapy for homozygous familial hypercholesterolemia. Journal of clinical lipidology, 2016; 10(4): 860–869.
32. RAAL FJ, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation, 2011; 124(20): 2202-7.
33. SANTOS RD, et al. Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia. The New England journal of medicine, 2020; 383(14): 1317–1327.
34. SCHWARZOVÁ L. Molekulár nígenetika hypercholesterolemie [Molecular genetics of hypercholesterolemia]. Vnitrnilekarstvi, 2016; 62(11): 877–881.
35. STEIN EA, et al. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation, 2013; 128(19): 2113–2120.
36. STEIN EA, et al. Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations. Journal of theAmerican College of Cardiology, 2017; 70(9): 1162–1170.
37. TROMP TR, et al. Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. Lancet, 2022; 399(10326): 719-728.
38. VARGHESE MJ. Familial hypercholesterolemia: A review. Annals of pediatric cardiology, 2014; 7(2): 107–117.
39. WERUTSKY CA. As bases moleculares das hipercolesterolemias familiares no Brasil: o Rio Grande do Sul [tese]. Ribeirão Preto: Faculdade de Medicina de Ribeirão Preto; 2006.
2. ALBERTO FL, et al. The Lebanese mutation as an important cause of familial hypercholesterolemia in Brazil. Brazilian Journal of Medical and Biological Research, 1999; 32(6): 739-45.
3. ALVES RJ, et al. Hipercolesterolemia familiar homozigótica e heterozigótica grave: epidemiologia, diagnóstico e tratamento. Revista da Sociedade de Cardiololgia do Estado de São Paulo, 2021; 31(1): 14-22.
4. BEHESHTI SO, et al. Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects. Journals of the American College of Cardiology, 2020; 75(20): 2553-66.
5. BEN-OMRAN T, et al. Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia. Advances in therapy, 2019; 36(7): 1786–1811.
6. BERBERICH AJ e HEGELE RA. Lomitapide for the treatment of hypercholesterolemia. Expert opinion on pharmacotherapy, 2017; 18(12): 1261–1268.
7. BRAAMSKAMP MJAM, et al. Efficacy and safety of rosuvastatin therapy in children and adolescents with familial hypercholesterolemia: Results from the CHARON study. J of clin lip, 2015; 9(6): 741–750.
8. CHORA JR, et al. Analysis of publicly available LDLR, APOB, and PCSK9 variants associated with familial hypercholesterolemia: application of ACMG guidelines and implications for familial hypercholesterolemia diagnosis. Genetics in medicine: official journal of the American College of Medical Genetics, 2018; 20(6): 591–598.
9. COIMBRA EM. Hipercolesterolemia familiar: das técnicas depurativas à terapêutica biológica. [Dissertação]. Lisboa. Universidade de Lisboa: Faculdade de Farmácia, Lisboa, 2020.
10. CUCHEL M, et al. European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. European heart journal, 2014; 35(32): 2146–2157.
11. DUARTE RAS. Hipercolesterolemi Familiar: uma nova abordagem no tratamento. [dissertação]. Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto, 2017.
12. FALUDI AA, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose – 2017. Arquivos Brasileiros de Cardiologia, 2017; 109(2, supl 1): 1-76.
13. FOODY JM e VISHWANATH R. Familial hypercholesterolemia/autosomal dominanthy percholesterolemia: Molecular defects, the LDL-C continuum, and gradients of phenotypic severity. Journal of clinical lipidology, 2016; 10(4): 970–986.
14. FRANCE M, et al. HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom. Atherosclerosis, 2016; 255: 128–139.
15. GIDDING SS, et al. American Heart Association Atherosclerosis, Hypertension, and Obesity in Young Committee of Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and Council on Lifestyle and Cardiometabolic Health. The Agenda for Familial Hypercholesterolemia: A Scientific Statement From the American Heart Association. Circulation, 2015; 132(22): 2167-2192.
16. GOSSIOS T, et al. Multimodal Treatment of Homozygous Familial Hypercholesterolemia. Current pharmaceutical design, 2018; 24(31): 3616–3621.
17. HARADA P, et al. Familial hypercholesterolemia prevalence in an admixed racial society: Sex T and race matter. The ELSA-Brasil. Atherosclerosis, 2018; (277): 273-77.
18. HARADA-SHIBA M, et al. Guidelines for Diagnosis and Treatment of Familial Hypercholesterolemia 2017. Journalofatherosclerosisandthrombosis, 2018; 25(8): 751–770.
19. IZAR, MCO et al. Atualização da Diretriz Brasileira de Hipercolesterolemia Familiar – 2021. Arquivo Brasileiro de Cardiologia, 2021; 117(4): 782-844.
20. KARR S. Epidemiology and management of hyperlipidemia. The American journal of managed care, 2017; 23(9 Suppl): S139–S148.
21. KHACHADURIAN AK. The Inheritance of Essential Familial Hypercholesterolemia. The American journal of medicine, 1964; 37: 402–407.
22. LEHRMAN MA, et al. The Lebanese allele at the low-density lipoprotein receptor locus. Nonsense mutation produces truncatedreceptor that is retained in endoplasmic reticulum. The Journal of biological chemistry, 1987; 262(1): 401–410.
23. MACH F, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European heart journal, 2020; 41(1): 111-188.
24. MAIO A, DOWD FJ. Familial Hypercholesterolemia. In: ENNA SJ, BYLUND DB (ed). xPharm: The Comprehensive Pharmacology Reference. Amsterdã: Elsevier, 2010; 6.
25. MILLAR JS, et al. Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production. Arteriosclerosis, thrombosis, and vascular biology, 2005; 25(3): 560–565.
26. MOLFETTA GA, et al. Mutational screening in the LDLR gene among patients presenting familial hypercholesterolemia in the Southeast of Brazil. Genetics and molecular research: GMR, 2017; 16(3): 1 0.4238/gmr16039226.
27. NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE (NICE). Familial hypercholesterolaemia: identification and management. London: NICE, 2019 Oct. (NICE Clinical Guidelines, No. 71).
28. NOHARA A, et al. Homozygous Familial Hypercholesterolemia. J Atheroscler Thromb., 2021; 28(7): 665-678.
29. PEREIRA AC, et al. I Diretriz Brasileira de Hipercolesterolemia Familiar (HF). Arquivos Brasileiros de Cardiologia, 2012; 99(2 suppl 2): 1–28.
30. RAAL FJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet, 2015; 385(9965): 341–350.
31. RAAL FJ, et al. Pediatric experience with mipomersen as adjunctive therapy for homozygous familial hypercholesterolemia. Journal of clinical lipidology, 2016; 10(4): 860–869.
32. RAAL FJ, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation, 2011; 124(20): 2202-7.
33. SANTOS RD, et al. Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia. The New England journal of medicine, 2020; 383(14): 1317–1327.
34. SCHWARZOVÁ L. Molekulár nígenetika hypercholesterolemie [Molecular genetics of hypercholesterolemia]. Vnitrnilekarstvi, 2016; 62(11): 877–881.
35. STEIN EA, et al. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation, 2013; 128(19): 2113–2120.
36. STEIN EA, et al. Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations. Journal of theAmerican College of Cardiology, 2017; 70(9): 1162–1170.
37. TROMP TR, et al. Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. Lancet, 2022; 399(10326): 719-728.
38. VARGHESE MJ. Familial hypercholesterolemia: A review. Annals of pediatric cardiology, 2014; 7(2): 107–117.
39. WERUTSKY CA. As bases moleculares das hipercolesterolemias familiares no Brasil: o Rio Grande do Sul [tese]. Ribeirão Preto: Faculdade de Medicina de Ribeirão Preto; 2006.