J Am Coll Cardiol 2007;50:2399–403 Prevalence of Fabry Disease in a Cohort of 508 Unrelated Patients With Hypertrophic Cardiomyopathy Lorenzo Monserrat,

Slides:



Advertisements
Similar presentations
Kate Thomson Molecular Genetics Laboratory, Oxford
Advertisements

MOLECULAR DIAGNOSIS OF FRAGILE X SYNDROME: A COMPILATION OF DATA OF 4,238 PATIENTS AND RELATIVES FROM 849 FAMILIES IN SPAIN M.Isabel Tejada (1); Josep.
ANNOUNCEMENTS  Homework #2 is due on Monday in lecture.  Change to 1b. Do not calculate a  2 value. Just calculate the expected phenotypic ratios if.
Heterozygous Fabry Disease Females Are Not Just “Carriers,” But Suffer From Significant Burden of Disease And Impaired Quality of Life Raymond Wang, M.D.
Genetic Diseases.
GENETIC TESTING : The analysis of chromosomes, DNA, proteins To detect abnormalities that may cause a genetic disease EXAMPLES OF GENETIC TESTING.
DOMENICO CORRADO, MD, PhD University of Padova, Italy
HEREDITARY HAEMOCHROMATOSIS. What Is It? An inherited disease characterised by excess iron deposition in various organs Leads to eventual fibrosis and.
Living Donor Kidney Transplantation in Hereditary Nephropathy Patients
 Genetic disease of heart muscle characterized by left ventricular hypertrophy in absence of another cardiac or systemic disease; variable morphologies.
Fragile x syndrome By Jordon Nagel.
Genetic Disorders & Diseases
Alport Syndrome Genetics and Diagnosis Martin Gregory, MD, PhD Professor of Medicine University of Utah Nothing to disclose.
Child with hematological dysfunction Emad Al Khatib, RN,MSN,CNS.
Initial presentation of multiple sclerosis in northern Iran; Is there any comparison to other countries Initial presentation of multiple sclerosis in northern.
Phenylketonuria (PKU) By: Greg Ancmon and Brennan Ramos Period 2.
Chapter 7 Genetic and Developmental Diseases. Review of Structure and Function Fertilization is the uniting of a sperm and ovum resulting in 23 pairs.
Hemophilia Research Center for Genetic Engineering and Biotechnology “Georgi D. Efremov”, MASA What is: Hemophilia is an X-linked congenital bleeding disorder.
Hemophilia A By Saad Mukaty. Definition of Hemophilia  Hemophilia (A) is a rare disorder in which blood doesn’t clot normally because it lacks important.
Inheritance and Human Genetics
Haemochromatosis in Norway Tanya Dholoo Karoline Lind Mjanger.
Molecular Genetics in the Von Willebrand disease Ghasem Rastegarlari.
Uterine Cancer Endometrial (or uterine) cancer will account for 50,000 new cases and 8200 deaths in the United States in Two genetic disorders are.
Cardiovascular Blueprint PANCE Blueprint. Dilated Cardiomyopathy Defined as being characterized by enlargement of chambers and impaired systolic function.
MAJOR EVENTS AND EVOLUTION IN CYSTIC FIBROSIS PATIENTS Author: Alexandra Martin Coordinator: Dr. Reka Borka Balas University of Medicine and Pharmacy Târgu-
Welcome 2/10-11/16 1. Turn in Quick Lab and Dihybrid Cross 2. Other Mendelian Genetics and Disorders Notes 3. Practice Non-Mendelian Genetics.
Don’t Worry I am Ok! Goal of project GOAL OF PROJECT  TO AWARE ABOUT HEART DISEASES.  TO UNDERSTAND CAUSES OF HEART DISEASES.  TO AWARE PREVENTIVE.
Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non- compaction, and septal defects by Lorenzo.
Date of download: 5/27/2016 Copyright © The American College of Cardiology. All rights reserved. From: Frequency and Phenotypes of Familial Dilated Cardiomyopathy.
ZOO405 by Rania Baleela is licensed under a Creative Commons Attribution- NonCommercial-ShareAlike 3.0 Unported LicenseRania BaleelaCreative Commons Attribution-
Global Fabry Disease Market Published: November 2014 Single User PDF: US$ 2500 Corporate User PDF: US$ 3500 Order this report by calling
Pedigrees 4/13/2010 Pedigrees The risks of passing on a genetic disorder to offspring can be assessed by genetic counseling, prenatal testing, and by.
Date of download: 7/7/2016 Copyright © The American College of Cardiology. All rights reserved. From: Correction J Am Coll Cardiol. 2014;63(2):
Date of download: 7/7/2016 Copyright © The American College of Cardiology. All rights reserved. From: Frequency and clinical expression of cardiac troponin.
Tay-Sachs Disease n What is it? n A degenerative neurological disorder where virtual absence of activity of a lysosomal enzyme, hexosaminidase A n Biochemistry.
GENETIC BASIS OF DISEASE- part 2. Genetic basis of disease part 2 objectives a. Define inborn errors of metabolism b. Describe the common characteristic.
Date of download: 9/19/2016 Copyright © The American College of Cardiology. All rights reserved. From: Novel Insight Into the Natural History of Short.
Cardiomyopathies Pavol Tomašov.
Mendelian Genetics Extended (5.2)
III. Endocrine Pancreas Diabetes Mellitus
Disclosures None.
Monogenic Disorders Genetic Counselling
Clinical characterization of six patients with 15q13. 2-q13
Figure 1: Questions included in questionnaire
Copyright © 2001 American Medical Association. All rights reserved.
Characterization of VHL promoter variants in patients suspected of Von Hippel Lindau Saleh Albanyan, Rachel Giles, Raymond H Kim, MD/PhD Division of.
Next-generation sequencing increases the diagnostic yield in aborted sudden cardiac death caused by hereditary heart disease   Brøndberg AK1, Christiansen.
Utility of Cardiac MRI in Diagnosing Fabry’s Cardiomyopathy
INTRODUCTION AIMS POPULATION AND METHODS RESULTS CONCLUSIONS
Hypertrophic Cardiomyopathy
Arrhythmogenic right ventricular dysplasia
HYPERTROPHIC CARDIOMYOPATHY(HCM)
Amicus Therapeutics & Galafold (migalastat) Jiri Hermanek, GM CEE
Different mode and types of inheritance
Volume 9, Issue 1, Pages (January 2012)
Figure 1 Cine cardiovascular magnetic resonance (CMR)
KEY CONCEPT A combination of methods is used to study human genetics.
Algorithm for the diagnosis of CF starting with the CFTR DNA test.
Population Structures
VWF sequence variants: innocent until proven guilty
X-linked inheritance Oliver Quarrell.
Baseline Characteristics of Cardiovascular Risk Factors and Selected Dietary Variables in a Cohort of 22,881 Men and 35,091 Women to Quintile of Fish Intakes.
High Incidence of Later-Onset Fabry Disease Revealed by Newborn Screening*  Marco Spada, Severo Pagliardini, Makiko Yasuda, Turgut Tukel, Geetha Thiagarajan,
Bar chart of systolic function in healthy individuals, HCM LVH− patients and HCM LVH+ patients. GLS was significantly worse in the HCM LVH+ patients compared.
Bar chart of cardiac volumes and EF in the healthy individuals, HCM LVH− patients and HCM LVH+ patients. Blue bars show the indexed diastolic volumes (EDVI.
Pedigrees and Inheritance Patterns
Diagnosis at presentation and diagnoses finally reached at the end of the inpatient admission. Diagnosis at presentation and diagnoses finally reached.
MUCOPOLYSACCHARIDOSIS-MPS
Presentation transcript:

J Am Coll Cardiol 2007;50:2399–403 Prevalence of Fabry Disease in a Cohort of 508 Unrelated Patients With Hypertrophic Cardiomyopathy Lorenzo Monserrat, Juan Ramon Gimeno-Blanes, Francisco Marin, Manuel Hermida-Prieto, Antonio Garcia-Honrubia, In maculada Pérez, Xusto Fernandez, Rosario de Nicolas, Gon zalo de la Morena, Eduardo Paya, Jordi Yagüe, Jesús Egido A Coruña, Murcia, Alicante, Barcelona, and Madrid, Spain

Introduction Fabry Disease X-linked inborn error of metabolism Deficient  -Galactosidase A (  -GAL A) enzyme activity Progressive globotriaosylceramide (GL-3) accumulation multiple cell types and tissues -- end organ impairment Progressive Multiple organ systems Morbidity Cardiac complication Stroke Renal failure Decreased lifespan

Inheritance Pattern

Fabry Disease - Symptoms Extreme Pain in Hands and Feet Angiocharatomas Stomach Pain & Digestive Problems High Risk of Heart Failure High Risk of Stroke, Hearing Loss & Vertigo Can not Tolerate Temperature Variations & Can not Sweat High Risk of Kidney Failure

0 Acroparesthesia Renal Disease CNS Disease Cardiac Disease [Age] 40+ Diagnosis (average) Clinical Presentation Fabry Disease Progression

Diagnosis of Fabry Disease Presumptive diagnosis observation of symptoms and laboratory findings family history/medical pedigree Definitive diagnosis enzyme assay in plasma, leukocytes, tears, or biopsied tissue Markedly deficient in affected males (very low to no enzyme activity) Carrier females can have low to normal levels Therefore it can be used to screen the males in a family but not the females gene mutation analysis or linkage analysis determine specific genetic mutation within family useful for precise carrier ID and prenatal diagnosis (therefore is diagnostic testing for women)

Introduction Hypertrophic cardiomyopathy more than 400 different mutations in genes encoding sarcomeric proteins 30% to 40% of the patients – cannot find these mutations Fabry disease as a relatively frequent cause of idiopathic left ventricular hypertrophy Prevalence of Fabry disease in a wide nonselected population of patients previously diagnosed with HCM

Materials and Methods Study protocol and patient enrollment 508 consecutive unrelated patients with HCM 3 regional centers (Coruña, in northern Spain; Murcia and Alicante, in southern Spain) all of the first-degree relatives were invited to be screened DNA from lymphocytes  -galactosidase A : assayed fluorometry -> activity GLA gene

Results

Table 1 Clinical Characteristics and Sudden Death Risk Factors of the Index Patients

Table 2 Summary of the Enzymatic and Genetic Screening of the Index Patients

Table 3 Genotype and Phenotype in the Index Patients With Low Enzymatic Activity

Figure 1 Pedigrees of the Families With Fabry Disease

Discussion 1% prevalence of FD in unselected patients with HCM Nakao et al. : 7 pts in 230 men with LVH (3%) Sachdev et al. : 6 pts in 153 men with HCM (4%) Ommen et al. : no FD Chimenti et al. : 4 pt in 34 women with HCM by endometrial Bx prevalence of HCM in the adult general population : 1 in 500 prevalence of FD in HCM : 1 in 100 prevalence of FD in the adult general population : 1 in 50,000

Discussion Screening :  -galactosidase A enzymatic activity Male : very low enzymatic activity Female carriers : within the normal range 7 women with a borderline activity (30% to 50% of the control) Several polymorphisms but no pathogenic mutation Classical (L89P, E358del) : early manifestation of the multisystemic disorder Late-onset (A143T) : in men with some residual plasma enzymatic activity or in female carriers S238N : incomplete penetrance in young carriers (even in men) plasma enzymatic activity measurement is cost-effective not only in men but also in women with HCM

Conclusion With a screening based on genotyping of patients with low plasma enzymatic activity, the prevalence of FD in our population with HCM was 1% (0.9% in men and 1.1% in women).