Wilson's disease ( Amgad Albanna ) .pptx

Fine Summary of Wilson's disease introduction, diagnosis and management , presented by Dr. Amgad Albanna

1. PRESENTED BY AMGAD NABEEL Healthcare Innovations Wilson’s Disease: Copper Overload Disease with Dr. Mokhtar Al- NahariSeminar HEPATO-LENTICULAR DISORDER !

2. 1 Introduction Provide an overview of Wilson's Disease, its significance, and prevalence. 2 Objectives Discuss the main goals and aims of improving diagnosis and treatment methods for Wilson's Disease. Agenda Key Points for Advancements in Diagnosis and Treatment of Wilson's Disease Healthcare

3. Copper in Ferroprotein Copper is a vital element in ferroprotein, influencing iron metabolism and melanin synthesis. Diverse Functional Roles Copper contributes to energy production, neurotransmitter synthesis, and central nervous system function . Dietary Copper Sources Key dietary sources of copper encompass shellfish , liver, nuts, legumes,beans , and organ meats . Introduction to Wilson’s Disease Unveiling the Role of Copper and Dietary Sources Copper Role & Dietary Sources

4. 1 Definition Wilson's disease is a rare genetic disorder that leads to copper accumulation in various organs, primarily the liver and brain. 2 Pathogenesis The disease is caused by mutations in the ATP7B gene, which impairs copper transport, resulting in its toxic buildup. 3 Clinical Picture Patients may present with liver disease, neurological symptoms, psychiatric manifestations, or a combination of these. 4 Diagnostics Diagnosis involves blood tests for copper levels, genetic testing for ATP7B mutations, liver biopsy, and imaging studies. OBJECTIVES Understanding the Core Aspects of Wilson's Disease Core Concepts

5. ATP7B Gene Mutations Autosomal recessive mutations occur in the ATP7B gene on chromosome 13 . DEFECTIVE ATP7B Protein Mutations lead to a defective ATP7B protein, reducing copper incorporation into apoceruloplasmin. Impact on Serum Copper Levels Reduced biliary copper excretion causes elevated free serum copper, leading to its accumulation in various organs. Pathogenesis of Wilson’s Disease Understanding the Genetic Basis and Copper Metabolism Genetic Basis & Copper Metabolism

6. 1 Jaundice Yellowing of the skin and eyes due to bilirubin build-up. 2 Hepatomegaly Enlargement of the liver beyond its normal size. 3 Edema Swelling caused by fluid retention, usually in the legs. 4 Ascites Abnormal accumulation of fluid in the abdominal cavity. 🦠 Which initially Considered of viral hepatitis and cirrhosis , and the diagnostics take place for . Clinical Picture: Hepatic Presentation Presentation of Wilson's Disease in the Liver Symptoms & Diagnosis Nausea Vomiiting Splenomegally ( may also occure )

7. Kayser -Fleischer Ring Approximately 95% of patients with neurologic signs exhibit the characteristic Kayser-Fleischer ring, contrasting with around 65% in those presenting with hepatic symptoms. Sun flower cataract Presence is not common like KfR but feature in the ocular presentation of Wilson's disease, aiding in diagnosis alongside the Kayser-Fleischer ring. Visual Impairment Visual impairment may occur due to cataracts or retinal degeneration in individuals with Wilson's disease, highlighting the impact of copper accumulation on ocular health. Clinical Picture: Ocular Presentation Key Characteristics of Ocular Manifestation in Wilson's Disease Ocular Manifestation Insights

8. Dystonia Rigidity Clinical Picture: Neuro Presentation Neurological Symptoms of Wilson's Disease Symptoms Overview Dysarthria Dystonia Rigidity

9. Tremor or Choreiform Movements Abnormal Gait Uncoordinated Handwriting Clinical Picture: Neuro Presentation Neurological Symptoms of Wilson's Disease Symptoms Overview

10. Personality Changes Common symptoms are characterized by alterations in personality, such as irritability, anger outbursts, and poor self-control. 1 Depression Patients often experience symptoms of depression, which can manifest as persistent feelings of sadness, hopelessness, and loss of interest in activities. 2 Anxiety Anxiety is prevalent among individuals with Wilson's Disease and can present as excessive worry, restlessness, and feelings of tension. 3 Clinical Picture: Psychiatric Presentation Understanding Psychiatric Symptoms in Wilson's Disease Psychiatric Symptoms

11. Delayed Puberty Renal Tubular Dysfunction Skeletal Effects Osteoarthritis Hemolytic Anemia Clinical Picture: Other Presentations Diverse Manifestations of Wilson's Disease Clinical Manifestations

12. Medical Diagnostics Innovations Diagnostics Advancements in Diagnostic Techniques for Wilson's Disease 1 FIRST TO ORDER LFTs 24-hours urinary copper slit- lamp examination Serum ceruloplasmin THEN YOU CAN COSIDER FBC Liver biopsy MRI brain NCC DNA test for mutation

13. Routine laboratory Studies Diagnostics: Biochemical/Laboratory Findings Exploring Essential Laboratory Tests for Wilson's Disease Diagnosis Diagnostic Insights Liver function test : ( AST and ALT ) Increase transaminases in 40-60% Bilirubin Elevated in approximately 12% Coobes-teast (for hemolytic anemia ) Negative coombes test Low albumin and prolonged INR In acute or chronic liver faliure

14. ↓ Serum ceruloplasmin (< 20 mg per dl ) ↑ 24-hour urine copper excretion(>100 micrograms) Optional ↓ Total serum copper ↑ Free serum copper Diagnostics: Copper Metabolism Studies Identifying Key Diagnostic Markers for Wilson's Disease Diagnostic Markers Must be in a copper free container Useful also in follow up of chelting agents Can be increase in inflammations as in acute stage Not measured before 6 months aged child (usually low in infant )

15. The presence of Kayser-Fleischer rings supports the suspicion of Wilson's Disease but their absence does not rule out the diagnosis . Diagnostic significance 2 Conduct a slit-lamp examination by a skilled professional to identify Kayser-Fleischer rings accurately . Kayser-Fleischer rings examination 1 Diagnostics: Kayser-Fleischer Rings Detection and Implications Diagnostic Insights

16. Liver Biopsy Consider liver biopsy if initial tests yield inconclusive results. Positive copper staining observed, although sensitivity may be low . More than 250microgram per gram dry wight of tissue is consistent with Wilson Hepatic Copper Concentration Levels exceeding 250 mcg/g (dry weight) suggest the presence of Wilson disease. Genetic Testing Recommended for screening first-degree relatives of Wilson disease patients or when initial diagnostic tests are inconclusive. Diagnostics: Advanced Studies Enhancing Diagnosis and Treatment Approaches for Wilson's Disease Diagnostic Techniques MRI BRAIN Hyper intensities in basal ganglia Uncommon but charecterstic pattern (GIANT PANDA appearane )

17. Diagnostic Score Proposal As diagnostic score was suggested by the working party at the 8th Leipzig, 2001, incorporating all available tests. International Meeting on Wilson's Disease n Diagnostic Score Proposal Ceruloplasmin level is not reliable single test as well as Kyser -fleshing ring may not be present as in many hepatic dominant presentation so * Acmbination of tests is needed Diagnostics: Diagnostic Score Advancements in Diagnosis via Diagnostic Score Diagnosis Advancements

18. CALL-TO-ACTION Medical Innovations Advancements in Diagnosis and Treatment of Wilson's Disease Innovative Approaches and Therapies 2

19. D- Penicillamine Facilitates copper removal through urine and prevents copper overload. Pyridoxine supplementation is prescribed to prevent Vitamin B6 deficiency . Trientine Hydrochloride Serves as an effective alternative for patients experiencing neurological complications due to penicillamine therapy. Trientine Hydrochloride Serves as an effective alternative for patients experiencing neurological complications due to penicillamine therapy. Treatment: Chelating Agents Enhancing Copper Excretion and Neurological Symptom Management Treatment Insights

20. Trientine Hydrochloride Serves as an effective alternative for patients experiencing neurological complications due to penicillamine therapy. Trientine Hydrochloride Serves as an effective alternative for patients experiencing neurological complications due to penicillamine therapy. Penicillamine Facilitates copper removal through urine and prevents copper overload. Pyridoxine supplementation is prescribed to prevent Vitamin B6 deficiency. Treatment: Chelating Agents Enhancing Copper Excretion and Neurological Symptom Management Treatment Insights

21. Increased Metallothionein Synthesis Zinc acetate enhances metallothionein synthesis, which reduces the absorption of dietary copper. Beneficial for Specific Patient Groups Particularly valuable for young, presymptomatic patients, pregnant patients, and for maintenance therapy. Treatment: Reduction of Copper Absorption Effectiveness of Zinc Acetate (Galzin) Therapy Therapeutic Efficacy

22. Advanced Stages Requirement Liver transplant is considered for advanced Wilson's disease stages that do not respond to medical treatments . Delayed Diagnosis Consequence In cases of delayed Wilson's disease diagnosis, where hepatic damage is irreversible, liver transplantation becomes necessary . Therapy Unresponsiveness When patients with Wilson's disease are unresponsive to medical therapy, liver transplantation may be the next viable option. Compliance and Hepatic Damage Poor patient compliance leading to severe hepatic damage may prompt the need for liver transplantation in Wilson's disease . Treatment: Liver Transplantation Consideration and Indications Liver Transplant Indications

23. Promising Results in Preclinical Model Demonstrated proof of principle in mouse model showcasing the potential effectiveness of adeno-associated virus-mediated ATP7B addition to hepatocytes. Targeting ATP7B Deficiency Focused approach on addressing ATP7B deficiency using gene therapy to enhance treatment outcomes in Wilson's disease. Treatment: Gene Therapy Implications of Adeno-Associated Virus-Mediated ATP7B Addition to Hepatocytes Medical Advances

24. CALL-TO-ACTION Medical Innovations Advancements in Diagnosis and Treatment of Wilson's Disease Innovative Approaches and Therapeutic Strategies 3

25. Consider Wilson's Disease Wilson’s Disease should be considered in individuals with liver abnormalities or neurological movement disorders of uncertain cause . Combined Symptoms Alert The disease must be considered in patients with unexplained liver disease combined with neurological or neuropsychiatric disorders . Diagnostic Evidence A low serum ceruloplasmin level is indicative of Wilson's Disease and should be taken as evidence for diagnosis . ( guid you for furthure evaluation ) Typical Biochemical Finding Stronge suggestive ceruloplasmin level is 5m per dL but below 20mg is low and need furthure evaluation Key Recommendations Essential Guidelines for Diagnosing Wilson's Disease Diagnostic Guidelines

26. Genetic Disorder Impacting Copper Metabolism Wilson’s Disease is a genetic disorder with an impact on copper metabolism within the body. Significance of Early Diagnosis and Treatment Early diagnosis and timely treatment are critical to prevent irreversible damage caused by Wilson's Disease. Comprehensive Diagnostic Approaches Diagnosis involves a blend of clinical signs assessment, biochemical tests, and advanced studies to confirm Wilson's Disease. Diverse Treatment Modalities Treatment options include chelating agents, zinc therapy, liver transplantation, and promising gene therapy for Wilson's Disease management. Summary of Key Takeaways Understanding Wilson's Disease Diagnosis and Treatment Advancements Healthcare

27. Empower Change Call to Action Empowering Actions for Wilson's Disease Wilson ’s disease! That’s it Thank you