Bempedoic acid: new evidence and recommendations on use.

PURPOSES OF REVIEW: Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide. Recognizing the importance of dyslipidemia treatment in the prevention of cardiovascular events has become a part of standard clinical practice. Desired values of LDL cholesterol (LDL-C) have become lower and lower in the last few decades, as evidenced by the most recent guidelines. Therefore, efforts to lower LDL cholesterol concentrations with conventional therapies and combinations of lipid-lowering therapy may not be successful in a high proportion of patients. RECENT FINDINGS: Bempedoic acid is a novel agent, first in-class ATP Citrate Lyase (ACL) inhibitor, which targets biosynthesis of the cholesterol in the liver. Considering the results of phase 3 studies, it has been approved for sole use for dyslipidemia treatment for patients who are statin-intolerant or in combination with statin-ezetimibe for those suffering from familial hypercholesterolemia or ASCVD and unable to reach targeted LDL-C values. SUMMARY: Bempedoic acid has proven beneficial for further reduction of LDL cholesterol for targeted groups of patients. It is not only efficient but also a well tolerated, affordable, and available agent whose place in lipid-lowering management is yet to be fully understood with new data collected from ongoing clinical research. In this review we suggest the place of bempedoic acid in lipid-lowering management.

Present and Future of Dyslipidaemia Treatment-A Review.

One of the greatest burdens on the healthcare systems of modern civilization is cardiovascular diseases (CVDs). Therefore, the medical community is looking for ways to reduce the incidence of CVDs. Simple lifestyle changes from an unhealthy to a healthy lifestyle are the cornerstone of prevention, but other risk factors for cardiovascular disease are also being currently targeted, most notably dyslipidaemia. It is well known that lowering serum lipid levels, and in particular lowering elevated LDL-cholesterol, leads to a reduction in major cardiovascular events. Although the focus to date has been on LDL-cholesterol levels and lowering them with statin therapy, this is often not enough because of increased concentrations of other lipoprotein particles in the serum and residual cardiovascular risk. Since lowering LDL-cholesterol levels is successful in most cases, there has been a recent focus on lowering residual cardiovascular risk. In recent years, new therapeutic options have emerged that target triglyceride-rich lipoproteins, lipoprotein (a) and apolipoproteins C and B. The effects of these drugs on serious adverse cardiovascular events are not yet known, but recent studies with some of these drugs have shown significant results in lowering total lipid levels. The aim of this review is to present the current therapeutic options for the treatment of dyslipidaemia and to describe the newly approved drugs as well as the drugs that are still in development. Although at this stage we cannot say with certainty whether these agents will be approved and widely used, it is safe to say that our views on the treatment of dyslipidaemia are certainly changing.

Achievement of ESC/EAS LDL-C treatment goals after an acute coronary syndrome with statin and alirocumab.

AIMS: European guidelines set low-density lipoprotein cholesterol (LDL-C) treatment goals <1.4 mmol/L after acute coronary syndrome (ACS), and <1.0 mmol/L for patients with recurrent cardiovascular events ≤2 years. Many ACS patients do not achieve these goals on statin alone. We examined actual goal achievement with alirocumab and projected achievement with ezetimibe, either added to optimized statin therapy. METHODS AND RESULTS: The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18 924 patients with recent ACS and hyperlipidaemia despite high-intensity or maximum-tolerated statin therapy. This subanalysis comprised 17 589 patients with LDL-C ≥1.4 mmol/L at baseline who did not receive ezetimibe treatment. High-intensity statin treatment was used in 88.8%. Median (interquartile range) baseline LDL-C was 2.3 (1.9-2.7) mmol/L. With alirocumab, 94.6% of patients achieved LDL-C <1.4 mmol/L at ≥1 post-baseline measurement vs. 17.3% with placebo. Among 2236 patients with a previous cardiovascular event within 2 years (before the qualifying ACS), 85.2% vs. 3.5%, respectively, achieved LDL-C <1.0 mmol/L. Among patients not treated with ezetimibe, we projected that its use would have achieved LDL-C <1.4 and <1.0 mmol/L in 10.6 and 0%, respectively, at baseline (assuming 18 ± 3% reduction of LDL-C). CONCLUSION: Among patients with recent ACS and LDL-C ≥1.4 mmol/L despite optimized statin therapy, the addition of alirocumab allowed 94.6% to achieve the 2019 European guideline LDL-C goal <1.4 mmol/L, and 85.2% of those with recurrent cardiovascular events to achieve <1.0 mmol/L. In contrast, the addition of ezetimibe to optimized statin therapy was projected to achieve LDL-C <1.4 mmol/L in only 10.6% of patients at baseline.

The landscape of Mucopolysaccharidosis in Southern and Eastern European countries: a survey from 19 specialistic centers.

BACKGROUND: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients. The landscape of MPS in Europe is not completely described and studies on availability of treatment show that ERT is not adequately implemented, particularly in Southern and Eastern Europe. In this study we performed a survey analysis in main specialist centers in Southern and Eastern European countries, to outline the picture of disease management in the region and understand ERT implementation. Since the considerable number of MPS IVA patients in the region, particularly adults, the study mainly focused on MPS IVA management and treatment. RESULTS: 19 experts from 14 Southern and Eastern European countries in total responded to the survey. Results outlined a picture of MPS management in the region, with a high number of MPS patients managed in the centers and a high level of care. MPS II was the most prevalent followed by MPS IVA, with a particular high number of adult patients. The study particularly focused on management and treatment of MPS IVA patients. Adherence to current European Guidelines for follow-up of MPS IVA patients is generally adequate, although some important assessments are reported as difficult due to the lack of MPS skilled specialists. Availability of ERT in Southern and Eastern European countries is generally in line with other European regions, even though regulatory, organizational and reimbursement constrains are demanding. CONCLUSIONS: The landscape of MPS in Southern and Eastern European countries is generally comparable to that of other European regions, regarding epidemiology, treatment accessibility and follow up difficulties. However, issues limiting ERT availability and reimbursement should be simplified, to start treatment as early as possible and make it available for more patients. Besides, educational programs dedicated to specialists should be implemented, particularly for pediatricians, clinical geneticists, surgeons, anesthesiologists and neurologists.

Prophylactic therapeutic plasma exchange in pregnant woman with Familial Chylomicronemia Syndrome - A case report.

CONTEXT: Familial Chylomicronemia Syndrome (FCS) is an inherited disease where lack of lipoprotein lipase results in severe hypertriglyceridemia that frequently leads to recurrent acute pancreatitis. Pregnancy in patients with familial chylomicronemia syndrome (FCS) post a risk for mother and baby with potential complications (pancreatitis, miscarriage and death). Therapeutic approach includes strict dietary measures and plasma exchange. Despite the development of new drugs for FCS, their safety in pregnancy has not yet been confirmed. CASE DESCRIPTION: We present a case of a young, pregnant female with FCS who had miscarriage in the past during one episode of acute pancreatitis. Due to the inability to achieve lower TG levels with current therapy, from 27-th week of pregnancy we have started prophylactic therapeutic plasma exchange (two times per week). Patient was followed up until the delivery of a healthy baby boy and did not experience an episode of acute pancreatitis. CONCLUSIONS: With adequate supervision and monitoring therapeutic plasma exchange represents a safe approach in pregnant women with FCS in order to reduce TGs and prevent pancreatitis. Therefore, we prevented potential complications for both mother and child.

Metabolic Syndrome, Morbidity and Mortlity - in the Era of COVID-19 Pandemic.

The prevalence of obesity, diabetes, arterial hypertension and cardiovascular and cerebrovascular diseases is increasing worldwide. Nowdays we are witnessing a pandemic of metabolic syndrome and obesity and an epidemic of these diseases in Croatia as well. Moreover, every second Croatian citizen dies because of cardiovascular diseases. Visceral obesity, diabetes, dyslipidemia and arterial hypertension tend to cluster forming a syndrome that we call metabolic syndrome. The concept of metabolic syndrome was defined several decades ago as visceral type of obesity, hypertriglyceridemia, low HDL-cholesterol, arterial hypertension and diabetes mellitus (insulin resistance). Most widely used definition is the one by National Education Cholesterol Program, NCEP - Adult treatment Panel III - ATP III . Therefore, visceral obesity is considered as one of the greatest risks for mortality worldwide. COVID pandemia increased the risk od deaths especially among patients with metabolic syndrome. Pandemia perpetuated several other socio-economical risk factors (stress, depression, physical inactivity, deviant behaviour...) which also strongly influence cardiovascular health. Unfortunately, SARS-COV-2 virus enters the host (human) cell using signaling pathways (ANG II Rc) known very well from the metabolic syndrome research and connecting those two entities predesponing these patients for a much worse prognosis when infected with SARS-COV-2 virus. To conclude - chronic obesity pandemia goes hand by hand with novel COVID-19 pandemia dramatiacally increasing the risk of severe morbidity and mortality.

Novel Experimental Agents for the Treatment of Hypercholesterolemia.

Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in most developed countries and even more in developing countries. Dyslipidemia is a well known main risk factor for ASCVD. Lipid-lowering treatment, particularly lowering LDL-cholesterol (LDL-C), can decrease the risk for ASCVD. New data and guidelines based upon them suggest that we should go with LDL-C levels as low as we can. Therefore, conventional lipid lowering agents (statins and statins+ezetimibe) are not enough mainly because of poor compliance and statin intolerance which is in the real world mostly pseudo-intolerance. PCSK9 inhibitors provided a new hope to further decrease LDL-C but are still expensive, they have to be injected subcutaneously twice a month and their long-lasting adverse effects are not known. Therefore, there is a constant need to develop novel, more potent, more safe, less expensive, more user friendly regimens of hypolipemic agents (bempedoic acid, selective PPAR alpha receptor modulators etc). One of the ways to overcome poor compliance and increase the potency of therapy with less adverse effects are fixed combinations of established drugs (statin+ezetimibe). The future of hypolipemic agents is based on antisense therapy, ie. the use of specific oligonucleotide sequences blocking the translation of the selected protein (targeting apolipoprotein CIII, lipoprotein (a), apolipoprotein B) or RNA silencing technique (PCSK9 mRNA) and are in various stages of clinical trials. Some of them are almost ready to use in everyday clinical practice. High risk and very high risk patients (eg. familial hypercholesterolemia, familial severe chylomicronemia syndrome) will benefit most. The aim of this review is to inform about novel hypolipemic agents - potent and safe drugs for dyslipidemia which should reduce the risk of ASCVD.

Prevalence of and risk factors for urolithiasis in Croatian patients with hemophilia.

Urolithiasis may be more prevalent in patients with hemophilia (PWH) than in age-matched non-hemophilic males. We conducted a cross-sectional evaluation of 92 adult PWH at University Hospital Center Zagreb. The primary objective was to investigate the frequency of urolithiasis in adult PWH, and the secondary objective was to determine associated risk factors. Urolithiasis was diagnosed by ultrasound and other patient- and hemophilia-related parameters were recorded. The prevalence of urolithiasis was significantly higher among PWH than the reported prevalence in the general Croatian population (10.9% vs 5.9%; P = 0.042). Similarly, the incidence of urolithiasis during the course of the disease was significantly higher than the estimated cumulative lifetime incidence of urolithiasis in the Croatian population (25% vs 12%; P = 0.001). Multivariate analysis showed that arterial hypertension, the presence of inhibitors, hypercalciuria and hyperbilirubinemia were independent predictors of current urolithiasis (P < 0.05), and that hematuria (P = 0.051) and prior urinary infections (P = 0.059) were also relevant factors.Urolithiasis is a significant burden in adult PWH. Identifying associated risk factors might help in establishing strategies for earlier recognition and more successful prevention and treatment of urolithiasis.

Acute pancreatitis after ocrelizumab treatment for relapsing remitting multiple sclerosis.

Ocrelizumab is an anti-CD20 monoclonal antibody used in the treatment of relapsing remitting and primary progressive multiple sclerosis. The main side effects are infusion-related with long term administration raising the risk of infections. During randomized controlled trials five cases of pancreatitis have been reported. We present a case of a patient with no risk factors for pancreatitis who after administration developed acute pancreatitis albeit with a good recovery.

Prevention of cardiovascular disease in patients with familial hypercholesterolaemia: The role of PCSK9 inhibitors.

Familial hypercholesterolaemia is an autosomal dominant inherited disorder characterised by elevated low-density lipoprotein cholesterol levels and consequently an increased risk of atherosclerotic cardiovascular disease (ASCVD). Familial hypercholesterolaemia is relatively common, but is often underdiagnosed and undertreated. Cardiologists are likely to encounter many individuals with familial hypercholesterolaemia; however, patients presenting with premature ASCVD are rarely screened for familial hypercholesterolaemia and fasting lipid levels are infrequently documented. Given that individuals with familial hypercholesterolaemia and ASCVD are at a particularly high risk of subsequent cardiac events, this is a missed opportunity for preventive therapy. Furthermore, because there is a 50% chance that first-degree relatives of individuals with familial hypercholesterolaemia will also be affected by the disorder, the underdiagnosis of familial hypercholesterolaemia among patients with ASCVD is a barrier to cascade screening and the prevention of ASCVD in affected relatives. Targeted screening of patients with ASCVD is an effective strategy to identify new familial hypercholesterolaemia index cases. Statins are the standard treatment for individuals with familial hypercholesterolaemia; however, low-density lipoprotein cholesterol targets are not achieved in a large proportion of patients despite treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to reduce low-density lipoprotein cholesterol levels considerably in individuals with familial hypercholesterolaemia who are concurrently receiving the maximal tolerated statin dose. The clinical benefit of PCSK9 inhibitors must, however, also be considered in terms of their cost-effectiveness. Increased awareness of familial hypercholesterolaemia is required among healthcare professionals, particularly cardiologists and primary care physicians, in order to start early preventive measures and to reduce the mortality and morbidity associated with familial hypercholesterolaemia and ASCVD.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Rationale and Design.

Familial hypercholesterolemia (FH) is a genetic disorder with well-known genetic transmission and clinical course. Despite great recent progress, FH is still underestimated, under-diagnosed and thus undertreated. Furthermore it represents a significant healthcare challenge as a common risk factor for the premature development of coronary heart disease. The ScreenPro FH Project is an international network project aiming at improving complex care - from timely screening, through diagnosis to up-to-date treatment of familial hypercholesterolemia in Central, Eastern and Southern Europe. An important task for the project is to harmonise and unify diagnostic and therapeutic approaches in participating countries, where the situation differs from country to country. Countries with more experience should serve as a model for countries developing the FH network.Key words: diagnosis - familial hypercholesterolemia - screening - treatment optimization.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Basic Epidemiology.

INTRODUCTION: Despite great recent progress, familial hypercholesterolemia (FH) is still underestimated, under-diagnosed and thus undertreated worldwide. We have very little information on exact prevalence of patients with FH in the Central, Eastern and Southern Europe (CESE) region. The aim of the study was to describe the epidemiological situation in the CESE region from data available. METHODS: All local leaders of the ScreenPro FH project were asked to provide local data on (a) expert guess of FH prevalence (b) the medical facilities focused on FH already in place (c) the diagnostic criteria used (d) the number of patients already evidenced in local database and (e) the availability of therapeutic options (especially plasma apheresis). RESULTS: With the guess prevalence of FH around 1 : 500, we estimate the overall population of 588 363 FH heterozygotes in the CESE region. Only 14 108 persons (2.4 %) were depicted in local databases; but the depiction rate varied between 0.1 % and 31.6 %. Only four out of 17 participating countries reported the the LDL apheresis availability. CONCLUSION: Our data point to the large population of heterozygous FH patients in the CESE region but low diagnostic rate. However structures through the ScreenPro FH project are being created and we can hope that the results will appear soon.Key words: diagnosis - epidemiology - familial hypercholesterolemia - screening.

Effects of statin therapy on augmentation index as a measure of arterial stiffness: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of statin therapy on augmentation index (AIx) as a measure of arterial stiffness using a meta-analysis of clinical trials. METHODS: The search included PubMed-Medline, Embase, SCOPUS, Web of Science and Google Scholar databases to identify randomized controlled trials investigating the effects of statin therapy on arterial stiffness measured as AIx. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential confounders. RESULTS: 18 trials examining the effects of statin therapy on arterial stiffness were included. A significant reduction in aortic AIx following statin therapy was proven (WMD: -2.40%, 95% CI: -4.59, -0.21, p=0.032; I(2): 51.20%). HR-adjusted AIx 75% values also revealed a significant improvement by statin therapy (WMD: -5.04%, 95% CI: -7.81, -2.27, p<0.001; I(2): 0%), but not when analysis was restricted to unadjusted AIx values (WMD: -2.30%, 95% CI: -4.83, 0.23, p=0.075; I(2): 53.83%). There was no significant change in carotid (WMD: -2.75%, 95% CI: -8.06, 2.56, p=0.309; I(2): 26.86%) and peripheral (WMD: 0.25%, 95% CI: -3.31, 3.82, p=0.889; I(2): 72.19%) AIx due to statin treatment. There was also no difference in the effect size calculated for different statins subgroups. The impact of statins on AIx was independent of LDL-cholesterol level (slope: 0.05; 95% CI: -0.02, 0.13; p=0.181). CONCLUSION: Statin therapy causes a significant reduction in aortic AIx which is independent of LDL-cholesterol changes.

[Management of mucopolysaccharidosis type VI in adults]. / SMJERNICE ZA LIJECENJE MUKOPOLISAHARIDOZE (MPS) VI U ODRASLIH BOLESNIKA.

Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome, MPS VI) is a progressive multisystemic lysosomal storage disease. Physical symptoms generally include growth retardation, and bone dysplasia. Enzyme replacement therapy is the treatment of choice and is done with recombinant version of enzyme N-acetylgalactosamine 4-sulfatase (galsulfase) which is administered intravenously. The enzyme replacement therapy should be applied once a week as a life-long treatment. Division of metabolic diseases, Department of internal medicine, University Hospital Center Zagreb continues with the treatment of MPS VI patients after they turn 18 years of life and are not treated any more by the pediatricians. The aim of this document is to provide the guidelines for diagnosis and management of adult patients with MPS VI which consists not only of regular galsulfase adiministration, but also of regular follow up and treatment of numerous comorbidities. These guidelines were produced by experts from the Division of metabolic diseases, Department of internal medicine, University Hospital Center Zagreb which is the Referral center for rare and metabolic diseases of the Ministry of Health, Republic of Croatia. The guidelines are result of collaboration with pediatricians, radiologists and biochemists without whose experience and advices appropriate treatment of these patients would not be possible. The guidelines were endorsed by the Croatian society for rare diseases, Croatian Medical Association.

[POMPE DISEASE - GUIDELINES FOR DIAGNOSIS AND MANAGEMENT OF ADULT PATIENTS]. / POMPEOVA BOLEST - SMJERNICE ZA DIJAGNOZU I LIJECENJE ODRASLIH BOLESNIKA.

These guidelines provide a short summary of recommendations on Pompe disease, how to diagnose this disease, management of adult patients with this disease, follow-up of the patients and recommendations on therapy and genetic testing. Early diagnosis and management of patients with Pompe disease requires a multidisciplinary approach of several different experts. These guidelines were produced by the Division of Metabolic Diseases, Department of Internal Medicine, University Hospital Center Zagreb which is a Referral expert center for rare and metabolic diseases of the Ministry of Health of the Republic of Croatia. They were endorsed by the Croatian Society for Rare Diseases, Croatian Medical Association.These are the first guidelines published in Croatia on diagnosis, treatment and follow-up of Pompe disease.

Thigh abscess as an extension of psoas abscess: the first manifestation of perforated appendiceal adenocarcinoma: case report.

A 65-year-old woman presented with a painful, swollen, red right thigh and the mild pain in the right abdomen without nausea, vomiting or diarrhoea that lasted for 1 week. Laboratory findings revealed elevated inflammatory markers. Computed tomography of the right thigh, abdomen and pelvis showed an abscess formation in the adductor muscles draining from the abscess that completely occupied the right retroperitoneum up to the diaphragm, dissecting downward through the inguinal canal. Appendix was enlarged with an appendicolith. Emergent exploratory laparotomy revealed a perforated appendix with psoas abscess. Pathohistological diagnosis revealed adenocarcinoma of the appendix. Thigh abscess is an uncommon condition with insidious clinical presentation. Therefore, early recognition and setting of the correct diagnosis enables adequate treatment avoiding additional complications and in some cases potential life-threatening conditions. When upper leg abscess is suspected or proven abdominal examination is mandatory.

Adiponectin is not associated with blood pressure in normotensives and untreated hypertensives with normal kidney function.

The role of adiponectin in hypertension is still a matter of debate. Obtained conflicting results could be mostly explained with diversity of subjects included in different studies. Our aim was to analyze association of adiponectin with blood pressure (BP) in a group of normotensive and untreated hypertensive subjects. Participants (N=257) were selected from a random sample of 2487 subjects enrolled in an observational cross-sectional study. Subjects with diabetes and chronic kidney diseases were excluded. BP was measured using Omron M6 device following ESH/ESC guidelines. Adiponectin concentration was determined by ELISA. There were no differences in adiponectin values (mg/L) between hypertensives and normotensives (median 9.75; iqr: 7.44-17.88 vs 11.35; iqr: 7.43-12.63; P=0.17). On univariate linear regression adiponectin was not associated with systolic or diastolic BP (P>0.05). Furthermore, multivariate analysis did not show significant contribution of log-transformed adiponectin either to systolic (ß=-0.040; P=0.43) or diastolic BP (ß=0.066; P=0.33). In our group of normotensives and untreated hypertensives with normal kidney function adiponectin was not associated with BP even after adjustment for other risk factors. Our results and conclusions should not be extrapolated to subjects with other characteristics.

[Gaucher disease--guidelines for diagnosis and management of adult patients]. / Gaucherova bolest--smjernice za dijagnozu i lijecenje odraslih bolesnika.

Gaucher disease is an autosomal recessive disorder, characterized by decreased levels of the lysosomal enzyme glucocerebrosidase. This deficiency results in a decreased breakdown of this glycosphingolipid glucocerebroside, which accumulates in the lysosomes of the monocyte-macrophage system. It is the most common form of sphingolipidosis. Clinically, the principle signs of Gaucher's disease are hepatosplenomegaly, bone involvement, hematological changes and CNS involvement. The diagnosis of Gaucher disease has to be confirmed by the measurement of the activity of the enzyme glucocerebrosidase in leukocytes or fibroblasts and genetic testing. An effective therapy for Gaucher disease has now been available for more than 10 years. It consists of life-long intravenous replacement of the deficient enzyme--glucocerebrosidase. If enzyme replacement therapy is started early enough, it leads to significant improvement in patient's general condition and quality of life. The aim of this document is to provide to the Croatian medical audience the guidelines for diagnosis and management of adult patients with Gaucher disease. These guidelines are produced by specialists who have long lasting experience with patients with rare metabolic diseases working in the Division of Metabolic Diseases, Department of Internal Medicine, University Hospital Center Zagreb which is the Referral Center for Rare and Metabolic diseases of the Ministry of Health, Republic of Croatia. They were endorsed by the Croatian Society for Rare Diseases, Croatian Medical Association. These are the first guidelines published in Croatia on diagnosis, treatment and follow-up of Gaucher disease.

[Fabry disease--guidelines for diagnosis and management of adult patients]. / Fabryjeva bolest- smjernice za dijagnozu i lijecenje odraslih bolesnika.

Early diagnosis and management of patients with Fabry disease (FD) requires a multidisciplinary approach of several different experts. The aim of this document is to provide health care professionals with guidelines for management of adult patients with Fabry disease. These guidelines were produced by the staff of the Division of Metabolic Diseases, Department of Internal Medicine, University Hospital Center Zagreb, which is the Referral Expert Center for Rare and Metabolic Diseases of the Ministry of Health, Republic of Croatia. The first guidelines ever published in Croatia concerning a rare metabolic disease are presented. This document provides a short summary on Fabry disease, how to diagnose Fabry disease, management of patients with this disease, follow-up of the patients, and gives recommendations on therapy and genetic testing.