Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
Mucopolysaccharidoses
Prof. Dr. Saad S Al Ani
Senior Pediatric Consultant
Head of Pediatric Department
Khorfakkan Hospital...
Mucopolysaccharidoses
Hereditary, progressive diseases caused by
mutations of genes coding for lysosomal
enzymes needed to...
Glycosaminoglycan(GAG)
A long-chain complex
carbohydrate composed
of:
1. Uronic acids
2. Amino sugars
3. Neutral sugars.
w...
Glycosaminoglycans(GAGs)
The major GAGs are:
1. Chondroitin -4- sulfate
2. Chondroitin -6- sulfate
3. Heparan sulfate
4. D...
Glycosaminoglycans (GAGs) (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
5
Major constit...
Proteoglycans degradation
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
6
www.glycoforum.gr.jp
...
Proteoglycans degradation disturbance
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
7
Absent or...
Proteoglycans degradation disturbance
(cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital8
pr...
Rule of fingers
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
9
Heparan sulfate
(impaired degra...
Mucopolysaccharidoses
Mucopolysaccharidoses are autosomal recessive
disorders, with the exception of Hunter disease,
which...
Mucopolysaccharidoses (cont.)
Overall frequency is between
3.5/100,000 and 4.5/100,000
3/1/2015
Mucopolysaccharidoses
Prof...
Sanfilippo Syndrome(MPSIII)
A deficiency in one of the enzymes required to
break down glycosaminoglycan heparan sulfate
(f...
Sanfilippo Syndrome (cont.)
• The incidence vary geographically, One per:
- 50000 people in the Netherlands
- 66000 people...
Sanfilippo Syndrome (cont.)
Deficiency in one of the four enzymes:
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Kh...
Sanfilippo Syndrome (cont.)
2.Alpha-N- acetylglucosaminidase (type B)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani...
Sanfilippo Syndrome (cont.)
3. Acetyl -Co Alpha- glucosaminide
acetyltransferase (type C)
3/1/2015
Mucopolysaccharidoses
P...
Sanfilippo Syndrome (cont.)
4.N- acetylglucosamine 6-sulfatase (type D)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al A...
Sanfilippo Syndrome (cont.)
Patients are characterized by slowly progressive,
severe CNS involvement with mild somatic
dis...
Sanfilippo Syndrome (cont.)
Presenting features include:
– Delayed development
– Hyperactivity with aggressive behavior
– ...
Sanfilippo Syndrome (cont.)
Severe neurologic deterioration occurs in most
patients by 6-10 yr of age, accompanied by rapi...
Sanfilippo Syndrome (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
21
ellendelbloggolo.b...
Sanfilippo Syndrome (cont.)
Delays in diagnosis of MPS III are common
due to :
- Mild physical features
- Hyperactivity
- ...
MPS 1
MPS I is caused by mutations of the IUA
gene on chromosome 4p16.3 encoding α-L-
iduronidase
3/1/2015
Mucopolysacchar...
MPS1 (cont.)
Deficiency of α-L- iduronidase results in a
broad clinical spectrum, from severe Hurler
disease to mild Schei...
Hurler Disease (MPS I)
This is a severe form of MPS I ,and it is
progressive disorder with multiple organ and
tissue invol...
Hurler Disease (cont.)
An infant with Hurler syndrome appears
normal at birth, but inguinal hernias are often
present
3/1/...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
27
www.eyecalcs.com
Most p...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
28
www.eyecalcs.com
Cardia...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
29
www.eyecalcs.com
Most c...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
30
www.eyecalcs.com
Headac...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
31
www.eyecalcs.com
Common...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
32
www.eyecalcs.com
Skelet...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
33
www.eyecalcs.com
Radio-...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
34
www.eyecalcs.com
With p...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
35
www.eyecalcs.com
Cont.
...
Hurler Disease (cont.) Diagnosis
Usually made between 6 and 24 mo of age
with evidence of:
– Hepatosplenomegaly
– Coarse f...
Hurler Disease (cont.) Diagnosis
-Prominent forehead
– Joint stiffness
– Short stature
– Skeletal dysplasia
3/1/2015
Mucop...
Hurler Disease (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
38
www.eyecalcs.com
Common...
Hunter disease (MPS II)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
39
Is an X-linked disorde...
Hunter disease (MPS II) (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
40
flipper.diff.o...
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
41
www.treypurcell.com
Hunter disease (MPS II) (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
42
flipper.diff.o...
Hunter disease (MPS II) (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
43
flipper.diff.o...
Hunter disease (MPS II) (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
44
flipper.diff.o...
Hunter disease (MPS II) (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
45
Patients with ...
Hunter disease (MPS II) (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
46
In severely af...
Hunter disease (MPS II) (cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
47
In both the mi...
Diagnosis of MPS
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
48
Any individual who is suspect...
Differential diagnosis
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
49
1.Mucolipidoses
2.Oligo...
Treatment of MPS
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
50
• Hematopoietic stem cell tra...
Hematopoietic stem cell transplantation
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
51
Clinic...
Hematopoietic stem cell transplantation
(Cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
5...
Hematopoietic stem cell transplantation
(Cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
5...
Hematopoietic stem cell transplantation (Cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
5...
Enzyme replacement
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
55
-It reduces :
• Organomegal...
Enzyme replacement (Cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
56
- It ameliorates :
...
Enzyme replacement (Cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
57
-The enzymes do not...
Prevention
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
58
• Primary prevention
Through geneti...
Prevention (Cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
59
Multidisciplinary attention...
Prevention (Cont.)
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
60
The progressive nature of c...
3/1/2015
Mucopolysaccharidoses
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
61
noahstjohn.com
Upcoming SlideShare
Loading in …5
×

Mucopolysaccharidoses

14,769 views

Published on

definition ,types,causes,presentations,most common types,diagnosis ,differential diagnosis ,treatment ,prevention

Published in: Health & Medicine
  • Follow the link, new dating source: ❶❶❶ http://bit.ly/39sFWPG ❶❶❶
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Dating for everyone is here: ❤❤❤ http://bit.ly/39sFWPG ❤❤❤
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Doctors Predicted I Would NEVER Stop Snoring But Contrarily to their Prediction, I Did It 100% Naturally! learn more... ♥♥♥ http://t.cn/AigiN2V1
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • I'm sleeping so much better! Hi David, just a quick message to say thank you so much for this. I have been using a CPAP machine for 3 years and I absolutely hate it. It's so uncomfortable and I sleep worse with it on than I do without it. I'm now sleeping much better thanks to your program. And my wife is so much happier too! ◆◆◆ http://ishbv.com/snoringno/pdf
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • I'm sleeping so much better! Hi David, just a quick message to say thank you so much for this. I have been using a CPAP machine for 3 years and I absolutely hate it. It's so uncomfortable and I sleep worse with it on than I do without it. I'm now sleeping much better thanks to your program. And my wife is so much happier too! ▲▲▲ http://t.cn/AigiCT7Q
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here

Mucopolysaccharidoses

  1. 1. Mucopolysaccharidoses Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital Sharjah ,UAE saadsalani@aol.com
  2. 2. Mucopolysaccharidoses Hereditary, progressive diseases caused by mutations of genes coding for lysosomal enzymes needed to degrade glycosaminoglycans (GAGs) (acid mucopolysaccharides). 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 2
  3. 3. Glycosaminoglycan(GAG) A long-chain complex carbohydrate composed of: 1. Uronic acids 2. Amino sugars 3. Neutral sugars. www.mun.ca 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 3
  4. 4. Glycosaminoglycans(GAGs) The major GAGs are: 1. Chondroitin -4- sulfate 2. Chondroitin -6- sulfate 3. Heparan sulfate 4. Dermatan sulfate 5. Keratan sulfate 6. Hyaluronan 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 4
  5. 5. Glycosaminoglycans (GAGs) (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 5 Major constituents of the ground substance of connective tissue, as well as nuclear and cell membranes
  6. 6. Proteoglycans degradation 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 6 www.glycoforum.gr.jp Proteoglycans Protein core Proteolytic Stepwise degradation GAG moiety
  7. 7. Proteoglycans degradation disturbance 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 7 Absent or grossly reduced activity of mutated lysosomal enzymes Proteoglycans Glycosaminoglycans (GAGs) Intralysosomal
  8. 8. Proteoglycans degradation disturbance (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital8 printablecolouringpages.co.uk Distended lysosomes cell function Characteristic pattern of clinical, radiologic, and biochemical abnormalities Specific diseases can be recognized that evolve from the intracellular accumulation of different degradation products
  9. 9. Rule of fingers 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 9 Heparan sulfate (impaired degradation) Mental deficiency Dermatan sulfate, Chondroitin sulfates, Keratan sulfate (impaired degradation) Mesenchymal abnormalities
  10. 10. Mucopolysaccharidoses Mucopolysaccharidoses are autosomal recessive disorders, with the exception of Hunter disease, which is X- linked recessive. 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 10
  11. 11. Mucopolysaccharidoses (cont.) Overall frequency is between 3.5/100,000 and 4.5/100,000 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 11 teamsanfilippo.org http://dxline.info/ Diseases /hurler- syndrome flipper.diff.org The most common subtype is Sanfilippo disease (MPS-III) followed by Hurler disease ( MPS-I ) And Hunter disease (MPS II
  12. 12. Sanfilippo Syndrome(MPSIII) A deficiency in one of the enzymes required to break down glycosaminoglycan heparan sulfate (found on the cell surface glycoproteins and also in extra-cellular matrix) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 12 http://www.primehealthchannel.com/sanfilippo-syndrome A rare form of lysosomal storage disease Inherited in an autosomal recessive pattern www.primehealthchannel.com
  13. 13. Sanfilippo Syndrome (cont.) • The incidence vary geographically, One per: - 50000 people in the Netherlands - 66000 people in Australia - 280000 cases in Northern Ireland 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 13 http://www.primehealthchannel.com/sanfilippo-syndrome www.internationalstudentinsurance.com www.gapyear.com www.carhirecomparison.ie
  14. 14. Sanfilippo Syndrome (cont.) Deficiency in one of the four enzymes: 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 14 1. Heparan N- sulfatase (type A)
  15. 15. Sanfilippo Syndrome (cont.) 2.Alpha-N- acetylglucosaminidase (type B) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 15
  16. 16. Sanfilippo Syndrome (cont.) 3. Acetyl -Co Alpha- glucosaminide acetyltransferase (type C) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 16
  17. 17. Sanfilippo Syndrome (cont.) 4.N- acetylglucosamine 6-sulfatase (type D) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 17
  18. 18. Sanfilippo Syndrome (cont.) Patients are characterized by slowly progressive, severe CNS involvement with mild somatic disease 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 18 Onset of clinical features usually occurs between 2 and 6 yr in a child who previously appeared normal.
  19. 19. Sanfilippo Syndrome (cont.) Presenting features include: – Delayed development – Hyperactivity with aggressive behavior – Coarse hair – Hirsutism – Sleep disorders – Mild hepatosplenomegaly 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 19 articleactive.com
  20. 20. Sanfilippo Syndrome (cont.) Severe neurologic deterioration occurs in most patients by 6-10 yr of age, accompanied by rapid deterioration of social and adaptive skills 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 20 ellendelbloggolo.blogspot.com
  21. 21. Sanfilippo Syndrome (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 21 ellendelbloggolo.blogspot.com Severe behavior problems such as: - Sleep disturbance - Uncontrolled hyperactivity - Temper tantrums - Destructive behavior - Physical aggression are common
  22. 22. Sanfilippo Syndrome (cont.) Delays in diagnosis of MPS III are common due to : - Mild physical features - Hyperactivity - Slowly progressive neurologic disease 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 22 rareshare.org
  23. 23. MPS 1 MPS I is caused by mutations of the IUA gene on chromosome 4p16.3 encoding α-L- iduronidase 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 23 www.patienthelp.org
  24. 24. MPS1 (cont.) Deficiency of α-L- iduronidase results in a broad clinical spectrum, from severe Hurler disease to mild Scheie diseases 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 24 www.patienthelp.org
  25. 25. Hurler Disease (MPS I) This is a severe form of MPS I ,and it is progressive disorder with multiple organ and tissue involvement that results in premature death, usually by 10 yr of age 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 25 www.eyecalcs.com
  26. 26. Hurler Disease (cont.) An infant with Hurler syndrome appears normal at birth, but inguinal hernias are often present 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 26 www.eyecalcs.com
  27. 27. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 27 www.eyecalcs.com Most patients have: • Recurrent upper respiratory tract and ear infections • Noisy breathing • Persistent copious nasal discharge
  28. 28. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 28 www.eyecalcs.com Cardiac involvement include: • Valvular heart disease: Mitral and Aortic valves incompetence • Coronary artery narrowing Obstructive airway disease, notably during sleep, may necessitate tracheotomy.
  29. 29. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 29 www.eyecalcs.com Most children with Hurler syndrome acquire social but only limited language skills because of : • Developmental delay • Combined conductive and neurosensory hearing loss • An enlarged tongue
  30. 30. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 30 www.eyecalcs.com Headache and sleep disturbance due to: Progressive ventricular enlargement with increased intracranial pressure caused by communicating hydrocephalus
  31. 31. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 31 www.eyecalcs.com Common eye involvement include: • Corneal clouding • Glaucoma • Retinal degeneration
  32. 32. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 32 www.eyecalcs.com Skeletal abnormalities include: • Enlarged, coarsely trabeculated diaphyses of the long bones • Irregular metaphyses and epiphyses
  33. 33. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 33 www.eyecalcs.com Radio-graphs show a characteristic skeletal dysplasia known as dysostosis multiplex The earliest radiographic signs are thick ribs and ovoid vertebral bodies http://www.keywordpicture.com/keyword/arthrogryposis%20multiplex http://www.maroteaux-lamy.com/Turkish/HCP/Bones.aspx
  34. 34. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 34 www.eyecalcs.com With progression of the disease macrocephaly develops, with: • Thickened calvarium • Premature closure of lambdoid and sagittal sutures • Shallow orbits
  35. 35. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 35 www.eyecalcs.com Cont. • Enlarged J-shaped sella • Abnormal spacing of teeth with dentigenous cysts
  36. 36. Hurler Disease (cont.) Diagnosis Usually made between 6 and 24 mo of age with evidence of: – Hepatosplenomegaly – Coarse facial features – Corneal clouding – Large tongue 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 36 www.eyecalcs.com nlm.nih.gov
  37. 37. Hurler Disease (cont.) Diagnosis -Prominent forehead – Joint stiffness – Short stature – Skeletal dysplasia 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 37 www.eyecalcs.com http://www.scripps.org/articles/99-frontal-bossing http://www.nemours.org/service/medical/skeletal-dysplasia http://doctorsgates.blogspot.ae http://emedicine.medscape.com/article/951148-overview
  38. 38. Hurler Disease (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 38 www.eyecalcs.com Common causes of death: • Obstructive airway disease • Respiratory infection • Cardiac complications
  39. 39. Hunter disease (MPS II) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 39 Is an X-linked disorder caused by the deficiency of iduronate-2-sulfatase (IDS) flipper.diff.org
  40. 40. Hunter disease (MPS II) (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 40 flipper.diff.org The gene encoding IDS is mapped to Xq28. Point mutations of the IDS gene have been detected in about 80% of patients with MPS II Hunter disease manifests almost exclusively in males. it has been observed in a few females
  41. 41. 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 41 www.treypurcell.com
  42. 42. Hunter disease (MPS II) (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 42 flipper.diff.org Patients with severe MPS II have features similar to those of Hurler disease except for: • Lack of corneal clouding • Slower progression of: Somatic and Central nervous system (CNS) deterioration
  43. 43. Hunter disease (MPS II) (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 43 flipper.diff.org Clinical manifestations: • Coarse facial features • Short stature • Dysostosis multiplex • Joint stiffness • Mental retardation manifest between 2 and 4 yr of age.
  44. 44. Hunter disease (MPS II) (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 44 flipper.diff.org The following may present • Grouped skin papules • Extensive Mongolian spots • Chronic diarrhea • Communicating hydrocephalus and spastic paraplegia
  45. 45. Hunter disease (MPS II) (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 45 Patients with the mild form have: • Prolonged life span • Minimal CNS involvement • Slow progression of somatic deterioration with preservation of intelligence in adult life flipper.diff.org
  46. 46. Hunter disease (MPS II) (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 46 In severely affected patients: • Extensive, slowly progressive neurologic involvement • Death, which usually occurs between 10 and 15 yr of age. flipper.diff.org
  47. 47. Hunter disease (MPS II) (cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 47 In both the mild and severe forms: • Airway involvement • Valvular cardiac disease • Hearing impairment • Carpal tunnel syndrome • Joint stiffness Are common and can result in significant loss of function flipper.diff.org
  48. 48. Diagnosis of MPS 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 48 Any individual who is suspected of an MPS disorder based on: • Clinical features • Radiographic results • Urinary GAG screening tests Should have a definitive diagnosis established by enzyme assay
  49. 49. Differential diagnosis 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 49 1.Mucolipidoses 2.Oligosaccharidoses In these conditions, the urinary excretion of GAGs is not elevated 3. Neurodegenerative and dwarfing conditions Mucopolysaccharidoses can be differentiate from them by the present of: • Hurler- like facial features • Joint contractures • Dysostosis multiplex • Elevated urinary GAG excretion
  50. 50. Treatment of MPS 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 50 • Hematopoietic stem cell transplantation results in significant clinical improvement of somatic disease in MPS I, II, and VI • Enzyme replacement using recombinant enzymes is approved for patients with MPS I, MPS II, and MPS VI.
  51. 51. Hematopoietic stem cell transplantation 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 51 Clinical effects include : • Increased life expectancy • Resolution or improvement of growth failure • Upper airway obstruction • Hepatosplenomegaly • Joint stiffness • Facial appearance
  52. 52. Hematopoietic stem cell transplantation (Cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 52 • Pebbly skin changes • Obstructive sleep apnea • Heart disease • Communicating hydrocephalus • Hearing loss
  53. 53. Hematopoietic stem cell transplantation (Cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 53 Enzyme activity in serum and urinary GAG excretion is normalized Transplantation prevents neurocognitive degeneration
  54. 54. Hematopoietic stem cell transplantation (Cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 54 Transplantation does not correct : • Existent cerebral damage • Skeletal and ocular anomalies
  55. 55. Enzyme replacement 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 55 -It reduces : • Organomegaly • Number of episodes of sleep apnea • Urinary GAG excretion
  56. 56. Enzyme replacement (Cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 56 - It ameliorates : • rate of growth • joint mobility • Physical endurance.
  57. 57. Enzyme replacement (Cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 57 -The enzymes do not: • Cross the blood-brain barrier • Prevent deterioration of neurocognitive involvement. -This therapy is the domain for patients with mild central nervous involvement
  58. 58. Prevention 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 58 • Primary prevention Through genetic counseling • Tertiary prevention To avoid or treat complications remains the mainstay of supportive pediatric care
  59. 59. Prevention (Cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 59 Multidisciplinary attention to: • Respiratory and cardiovascular complications • Hearing loss • Carpal tunnel syndrome • Spinal cord compression • Hydrocephalus, and other problems Can greatly improve the quality of life for patients and their families
  60. 60. Prevention (Cont.) 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 60 The progressive nature of clinical involvement in MPS patients dictates the need for specialized and coordinated evaluation
  61. 61. 3/1/2015 Mucopolysaccharidoses Prof.Dr.Saad S Al Ani Khorfakkan Hospital 61 noahstjohn.com

×