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Hunter Syndrome

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Hunter Syndrome

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  1. <?xml version="1.0"?><AllQuestions><Question><slideID>367</slideID><slideType>Q&amp;A_QSlide</slideType><questionText>Thinking of patients with Hunter syndrome in your practice that have cardiovascular signs and symptoms, which of these is the most common?</questionText><teamScoringFlag>True</teamScoringFlag><correctValue>0</correctValue><incorrectValue>0</incorrectValue></Question><Question><slideID>368</slideID><slideType>Q&amp;A_QSlide</slideType><questionText>Based on the recommended evaluations and testing intervals for the different organ systems just presented, will you change any aspect of how your Hunter patients are evaluated?</questionText><teamScoringFlag></teamScoringFlag><correctValue></correctValue><incorrectValue></incorrectValue></Question></AllQuestions> <?xml version="1.0"?><Settings><answerBulletFormat>Alpha</answerBulletFormat><answerNowAutoInsert>No</answerNowAutoInsert><answerNowStyle>Explosion</answerNowStyle><answerNowText>Answer 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<?xml version="1.0"?><TeamNames><Team1></Team1><NewTeam1></NewTeam1><Team2></Team2><NewTeam2></NewTeam2><Team3></Team3><NewTeam3></NewTeam3><Team4></Team4><NewTeam4></NewTeam4><Team5></Team5><NewTeam5></NewTeam5><Team6></Team6><NewTeam6></NewTeam6><Team7></Team7><NewTeam7></NewTeam7><Team8></Team8><NewTeam8></NewTeam8><Team9></Team9><NewTeam9></NewTeam9><Team10></Team10><NewTeam10></NewTeam10></TeamNames> <?xml version="1.0"?><SlideMaster><tagSlideID>368</tagSlideID><slideID></slideID></SlideMaster> <?xml version="1.0"?><AllAnswers><Answers><slideID>367</slideID><answerID>0</answerID><answerText>Valve disease</answerText><isCorrect>Yes</isCorrect><pointValue>100</pointValue></Answers><Answers><slideID>367</slideID><answerID>1</answerID><answerText>Arrhythmia</answerText><isCorrect>None</isCorrect><pointValue>0</pointValue></Answers><Answers><slideID>367</slideID><answerID>2</answerID><answerText>Cardiomyopathy</answerText><isCorrect>None</isCorrect><pointValue>0</pointValue></Answers><Answers><slideID>367</slideID><answerID>3</answerID><answerText>Congestive heart failure</answerText><isCorrect>None</isCorrect><pointValue>0</pointValue></Answers><Answers><slideID>368</slideID><answerID>0</answerID><answerText>Yes, I plan to include additional evaluations</answerText><isCorrect>None</isCorrect><pointValue>0</pointValue></Answers><Answers><slideID>368</slideID><answerID>1</answerID><answerText>Yes, I plan to increase the frequency of testing</answerText><isCorrect>None</isCorrect><pointValue>0</pointValue></Answers><Answers><slideID>368</slideID><answerID>2</answerID><answerText>Yes, I plan to include additional evaluations and increase the</answerText><isCorrect>None</isCorrect><pointValue>0</pointValue></Answers><Answers><slideID>368</slideID><answerID>3</answerID><answerText>No, I am satisfied with the current evaluation process</answerText><isCorrect>None</isCorrect><pointValue>0</pointValue></Answers></AllAnswers> Hunter Syndrome

  2. What is Hunter Syndrome? • Hunter syndrome (or MPS II) is an inherited Iysosomal storage disease1 • First described by Charles Hunter in 19172 • Estimated worldwide incidence of 1:154,770 total live births3-11 1Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, et al (eds). The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill; 2001:3421–3452; 2Hunter C. Proc R Soc Med.1917;10:104–116; 3Baehner et al. J Inherit Metab Dis. 2005;28:1011–1017; 4Poorthuis et al. Hum Genet. 1999;105:151–156; 5Meikle et al. JAMA. 1999;281:249–254; 6Pinto et al. Eur J Hum Genet. 2004;12:87–92; 7Applegarth et al. Pediatrics. 2000;105:e10; 8Lowry et al. N Engl J Med. 1971;284:221–222; 9Lowry et al. Hum Genet. 1990;85:389–390; 10Michelakakis et al. Genet Couns. 1995;6:43–47; 11Nelson. Hum Genet. 1997;101:355–358.

  3. GAG Accumulation1 GAG I2S cleavage site I2S = iduronate-2-sulfatase lysosomes M6P receptor transportvesicle nucleus GAG ER Golgi In the absence of I2S, the GAG degradation pathwayis blocked and lysosomes fill up with GAG. 1. Neufeld, Muenzer. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3421–3452.

  4. Scenarios of Hunter Syndrome Inheritance MOST LIKELY: Female carrier passes onHS I2S gene to son1 LESS COMMON BUT POSSIBLE: Hunter syndrome male passes onHS I2S gene to daughter1 1Neufeld, Muenzer. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3421–3452.

  5. Preliminary Diagnosis of Hunter Syndrome • Preliminary analysis of urinary GAG levels1,2 • Does not differentiate between phenotypes in the clinical spectrum • Does not differentiate between different mucopolysaccharidoses unless electrophoresis is performed • Accurate urinary samples may be difficult to obtain • Due to the frequency of false negatives, a negative result cannot exclude a diagnosis2 1Neufeld, Muenzer. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3421–3452. 2Braverman. Mucopolysaccharidosis type II. eMedicine Journal [serial online]. 2006.

  6. Confirming a Diagnosis of Hunter Syndrome • Bone radiography reveals characteristic bone changes1 • Skeletal radiography to look for signs of dysostosis multiplex1 • Definite diagnosis achieved by measuring I2S activity in white blood cells, skin fibroblasts, or serum1 • Molecular testing is important for identifying carriers in family • Prenatal diagnosis may be made from amniotic fluid when family has history of Hunter syndrome1,2 1Braverman. Mucopolysaccharidosis type II. eMedicine Journal [serial online]. 2006. 2Neufeld, Muenzer. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3421–3452.

  7. Importance of Early Diagnosis • Hunter syndrome is a severe and progressive disorder • Over time, patients may experience irreversible damage to organs and systems • In severe cases, death can occur in the teens; in milder cases patients can live into their 50s or 60s

  8. Clinical Spectrum of Hunter Syndrome Neufeld, Muenzer. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3421–3452. Photograph (left) reprinted with permission from the authors and McGraw-Hill. Photograph (right) is taken from the Shire Human Genetic Therapies library of images.

  9. Signs and Symptoms: Craniofacial • Coarsening1,2 • Macroglossia1,2 • Deafness and recurrent ear infections3 • Chronic rhinorrhea1 1Neufeld, Muenzer. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3421–3452. 2Braverman. Mucopolysaccharidosis type II. eMedicine Journal [serial online]. 2006. 3Finlayson. Pediatr Dermatol. 1990;7:150–152.

  10. Signs and Symptoms: Skeletal • Joint stiffness, restriction, and contractures • Camptodactyly • Bone dysplasia • Joint pain X-ray of 18-year old patient with mucopolysaccharidosis type II showing femoral head necrosis and the typical features of dysostis multiplex Neufeld, Muenzer. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3421–3452.

  11. Signs and Symptoms: Neurologic • Cognitive impairment1/hyperactivity in some patients1 • Progressive mental retardation in many patients1 • Communicating hydrocephalus1,2,3 • Spinal cord compression4 • Carpal tunnel syndrome1,2,5 1Braverman. Mucopolysaccharidosis type II. eMedicine Journal [serial online]. 2006. 2Neufeld, Muenzer. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3421–3452. 3Van Aerde et al. Acta Paediatr Belg. 1981;34:93–96. 4Ballenger et al. AnnNeurol. 1980;7:382–385. 5Norman-Taylor et al. J Pediatr Orthop B. 1995;4:106–109.

  12. Signs and Symptoms: Cardiovascular • Valve disease1 • Pulmonary hypertension1 with secondary congestive heart failure • Biventricular hypertrophy with cardiomyopathy1 • Arrhythmias1 • Congestive heart failure1,2 1Kettles et al. Cardiovasc Pathol. 2002;11:94–96. 2Braverman. Mucopolysaccharidosis type II. eMedicine Journal [serial online]. 2006. 3Wraith et al. Genet Med. 2008;10(7):508–516.

  13. Signs and Symptoms: Pulmonary • History of frequent pneumonias1 • Restrictive lung disease due to small rib cage and stiff joints1 • Upper airway obstruction/sleep apnea1 • Tracheobronchomalacia1 • Respiratory insufficiency1,2 • Increased risk during anesthesia2 1Morehead, Parsons. Int J Pediatr Otorhinolaryngol. 1993;26:255–261. 2Braverman. Mucopolysaccharidosis type II. eMedicine Journal [serial online]. 2006.

  14. Signs and Symptoms: Gastrointestinal • Abdominal distension1 • Hepatosplenomegaly1 • Umbilical and inguinal hernias1 • Watery diarrhea2 1Braverman. Mucopolysaccharidosis type II. eMedicine Journal [serial online]. 2006. 2Neufeld, Muenzer. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3421–3452.

  15. Coordinating Care in Patients With Hunter Syndrome • Management requires multidisciplinary approach • Neurologic involvement • Hydrocephalus, spinal cord compression, atlantoaxial instability, cognitive involvement, carpal tunnel syndrome (CTS) • Cardiac involvement • Valvular dysfunction, conduction abnormalities • Respiratory involvement • Upper-airway obstruction, pharyngomalacia/tracheomalacia, restrictive lung disease, obstructive sleep apnea • Skeletal involvement • Coxa valga deformity, joint contractures, trigger fingers due to CTS • Hearing • Chronic otitis media, ostosclerosis, neurosensory loss • Eye • Retinal dysfunction Muenzer J et al. Pediatrics. 2009;1241:e1–e12.

  16. Recommended Evaluations for Hunter Syndrome From an International Panel of Physicians Muenzer J et al. Pediatrics. 2009;1241:e1–e12.

  17. Recommended Evaluations for Hunter Syndrome From an International Panel of Physicians(cont) Muenzer J et al. Pediatrics. 2009;1241:e1–e12.

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