| Abstract | Porodična hiperkolesterolemija (FH) je autosomno dominantno nasljedna bolest uzrokovana mutacijama gena LDLR. U rjeđim slučajevima, bolest uzrokuju mutacije gena APOB ili PCSK9. Mutacije se mogu očitovati nedovoljnom sintezom receptora ili poremećajem njegove funkcije. Rezultat navedenoga je nedovoljna razgradnja lipoproteina niske gustoće (LDL) i porast njegove koncentracije u plazmi što dovodi do rane i ubrzane aterogeneze. Incidencija heterozigotnog oblika FH iznosi 1:200 do 1:250, što je čini najčešćom nasljednom bolešću. Teži, homozigotni oblik bolesti je puno rjeđi, a incidencija mu je 1:1 000 000. Početak pojave simptoma proporcionalan je koncentraciji LDL-a u krvi. U heterozigota se najčešće javljaju u ranijoj odrasloj dobi u obliku koronarne bolesti dok se odlaganje kolesterola oko tetiva (tendinozni ksantomi), iznad zglobova (tuberozni ksantomi) i u kožu vjeđa (ksantelazme) rijetko javlja prije odrasle dobi. U homozigota se ksantomi javljaju već u prvim godinama života, a kardiovaskularna bolest se obično manifestira prije desete godine života. Prepoznavanje FH u dječjoj dobi vrlo je važno s obzirom da razvoj bolesti traje od rođenja, a promjene na krvnim žilama vide se već i u djece. S obzirom na visoku učestalost, predstavlja veliki javnozdravstveni problem. Komplikacije bolesti mogu se spriječiti prepoznavanjem zahvaćenih obitelji, kaskadnim probirom i provođenjem preventivnih mjera već u dječjoj dobi. Bolest se u djece najčešće prepozna slučajno, nalazom povišene koncentracije LDL-a ili nakon što se bolest potvrdi u člana obitelji, a u rjeđim slučajevima nakon razvoja ranih kliničkih pokazatelja ateroskleroze. Dijagnoza se može potvrditi fenotipski ili analizom gena LDLR. Ako je nalaz negativan, gensku analizu treba proširiti na gene za apoB i PCSK9. Osnova liječenja je održavanje koncentracije LDL-a ispod 3,5 mmol/L. To se prvenstveno postiže regulacijom prehrane i tjelesnom aktivnošću, uz prevenciju pušenja i pretilosti. Obično se oko osme godine života započinje liječenje statinima. U novije vrijeme koristi se i ezetimib koji inhibira apsorpciju kolesterola u crijevima. U homozigota se rano primjenjuje afereza lipoproteina, a u najtežim slučajevima može se učiniti i transplantacija jetre. Uz terapiju osnovne bolesti, važne su i redovite kontrole koje uključuju procjenu progesije kardiovaskularne bolesti. |
| Abstract (english) | Familial hypercholesterolemia (FH) is an inherited autosomal dominant disease caused by mutations of LDLR gene. The disease is in fewer cases caused by mutations of genes APOB or PCSK9. Mutations can be manifested by insufficient receptor synthesis or functionality disorders. This results in the insufficient low-density lipoprotein (LDL) breakdown and the increase of its plasma levels which leads to early and rapid atherogenesis. The incidence of FH in heterozygotes amounts to 1:200 to 1:250, which makes it the most common hereditary disease. More severe, homozygous form of disease is much rarer, with its incidence being 1:1 000 000. The onset of symptoms is proportional to LDL blood concentrations. In heterozygotes, the symptoms most often appear in early adulthood in the form of coronary disease, while cholesterol deposits around tendons (tendon xanthomas), above joints (tuberous xanthomas), and in the eyelids (xanthelasma) rarely occur before adulthood. In homozygotes, xanthomas appear in the first years of life, while the cardiovascular disease is usually manifested before the tenth year of life. It is very important to recognize FH in childhood considering that disease development starts from birth, and blood vessel changes can be seen even in children. Due to the high incidence, FH represents an important public health issue. However, the complications of the disease can be prevented by the identification of affected families, cascade screening, and enforcement of preventive measures already at a young age. The disease in children is most commonly established by chance, after identifying high LDL blood concentrations or after a family member gets diagnosed, or, in rare cases, after the development of early clinical manifestations of atherosclerosis. The diagnosis can be confirmed phenotypically or with LDLR gene analysis. If the test is negative, the analysis should be extended to genes for apoB and PCSK9. The basis of treatment is maintaining LDL concentrations below 3,5 mmol/L. That is primarily achieved by diet and regular physical activity, with smoking and obesity prevention. Usually, around the eighth year of life treatment with statins begins. Since recently ezetimibe is used which inhibits intestinal cholesterol absorption. In homozygotes, lipoprotein apheresis is implemented early, and in the most severe cases liver transplantation may be performed. Beside the treatment, it is important that patients have regular follow-ups that include cardiovascular disease progression assessment. |
