1. 1. Clinical Case Presentation Dr. Safeer Ahmed Jamil FCPS II Trainee Pediatrics
2. 2. Case Report A 3 year old male boy presented in ER with c/o Fever 5d Cough and flu 5d Discharge from rt. Ear 3d No associated hx of vomiting L/stools, altered sensorium or seizures, pain abdomen or any of urinary symptoms First born ,nonconsangious marriage, SVD @ terms.. ok Vaccinated Developmentally delayed just achieved standing with support Treated multiple times for RTI .. operated for umbilical hernia at the age of 1 year Systemic inquiry off n on loose stools ..progressive slowly distended abdomen
3. 3. Case Report General Physical Appearance;- sick looking child comfortable in mothers lap with prominent forehead, depressed nasal bridge and coarse facial features, fine corneal clouding Growth Parameters Weight 14kg (50th centile) Height 65 cm(below 5th centile) Ofc 53cm (@75th cetile) Vitals Pulse 108/min Temp 103f R/R 38/min Child was pale to look at ..no lymph nodes palpable
4. 4. Case Report SYSTEMIC EXAM REVEALS CNS;- Intact CVS;- good peripheral pulses ,S1+S2+PSM at apex 3/4radiating to axilla no heave Respiration;- HVB+conducting sound no distress GIT:- Soft to firm abdomen Liver palpable 3cm BCM (12 cm) Spleen palpable 2cm BCM(9cm) Bowl sounds are audible Examination of MS system reveals contractures and limited mobility at ankle and wrist joint no pain, erythema, redness over joint.
5. 5. Diagnosis/Differentials
6. 6. Hurler Disease MUCOPOLYSACCHARIDOSES
7. 7. Definition Mucopolysaccharidoses are hereditary, progressive diseases caused by mutation of gene coding the lysosomal enzymes needed to degrade glycosaminoglycans result in there deposition in different organs and leads to clinical manifestations
8. 8. Glycosaminoglycans(GAGs) A long-chain complex carbohydrate composed of: Uronic acids Amino sugars Neutral sugars. The major GAGs are: 1. Chondroitin -4- sulfate 2. Chondroitin -6- sulfate 3. Heparan sulfate 4. Dermatan sulfate 5. Keratan sulfate 6. Hyaluronan
9. 9. Rule of fingers Heparan sulfate (impaired degradation) Mental deficiency Dermatan sulfate, Chondroitin sulfates, Keratan sulfate (impaired degradation) Mesenchymal abnormalities
10. 10. Clinical manifestations ..(MPS)
11. 11. HURLER DISEASE (MPS I) Autosomal recessive disorder Deficiency of a-L-iduronidase Usually present at 6-24 months FEATURES Coarse facial features Large tongue, prominent forehead Short stature Joint stiffness Skeletal dysplasia (Dysostosis Multiplex) Cardiomyopathy Communicating hydrocephalus Corneal clouding/Retinal detachment Death usually by CV and respiratory complications
12. 12. HURLER DISEASE (MPS I) Dysostosis Multiplex Thick ribs/Bullet shape prox. MC Ovoid vertebral bodies ( beaking of vertebra ) Coarse trabeculated diaphysis/ Irregular epiphysis and metaphysis Macrocephaly with thick calvarium premature closure of sutures shallow orbit and J shaped sella terrcica Abnormal spacing of teeth with gingival hyperplasia and dentigenous cyst HURLE-SCHEIE DISEASE :- Less sever ,Progressive somatic involvement ,No intellectual dysfunction SCHEIE DISEASE Mild form ,Normal intelligence and stature (10-20 yrs)
13. 13. 17
14. 14. HUNTER DISEASE(MPS II) X-linked Recessive.exclusively in males Iduronate -2-sulfatase Features similar to Hurler disease except for lack of corneal clouding and slower progression of somatic and central nervous system deterioration Skin papules Chronic diarrhea Communicating hydrocephalus and spastic paraplegia due to thickening of meninges Carpal tunnel syndrome Death by 10-15 years of age
15. 15. SANFILIPPO DISEASE(MPS III) Heparan sulfate accumulation 4 subtypes A,B,C ,D Most common type of MPS Slowly progressive mild somatic and sever disproportionate involvement of CNS Features ..(2-6 years) Delayed development Hyperactivity with aggressive behavior Coarse hair ,hirsutism Mild hepatosplenomegaly Sleep disturbance
16. 16. MORQUIO DISEASE (MPS IV) N-Aetyle-GlactosamineSulfatase Defeciencykeraten sulfate 2 subtyypes A (sever) & B(mild) Features Short trunk dwarfism Fine corneal clouding hepatomegaly Characteristic skeletal dysplasia (genu valgus ,kyphosis ,short trunk and neck, wedling gait, tendency to fall) cervical myelopathy (atlanto-axial dislocation)
17. 17. MAROTEAUX-LAMY DISEASE(MPS VI) Arylsulfatase B deficiency Dermatan sulfate accumulation FEATURES Similar to Hurler Spinal cord compression from thickening of Dura in upper cervical canal Intelligence is usually normal, but visual and hearing impairments are present
18. 18. SLY SYNDROME(MPS VII) B Glucronidase Defeciency Intracellular storage of GAG fragments (coarse granulocytic inclusions ) Features Lethal non immune hydrops fetalis Thick skin Visceromegaly Dysostosis multiplex Normal intelligence and cornea is clear MPS IX.. Hyaluronan. .Mild , short stature , Visceromegaly ,normal joint movements normal intelligence
19. 19. Differential diagnosis 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
20. 20. Diagnosis 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 s/leukocytes or skin fibroblast Perinatal diagnosis:- cultured cells from amniotic fluid or chorionic villous biopsy
21. 21. Treatment of MPS 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.
22. 22. Hematopoietic stem cell transplantation Clinical effects includes : Increased life expectancy Resolution or improvement of growth failure Upper airway obstruction Hepatosplenomegaly Joint stiffness Facial appearance Pebbly skin changes(Hunter disease) Obstructive sleep apnea Heart disease Communicating hydrocephalus Hearing loss
23. 23. Hematopoietic stem cell transplantation(Cont.) Enzyme activity in serum and urinary GAG excretion is normalized Transplantation prevents neurocognitive degeneration Transplantation does not correct : Existent cerebral damage Skeletal and ocular anomalies
24. 24. Enzyme replacement It reduces : Organomegaly Number of episodes of sleep apnea Urinary GAG excretion It ameliorates : rate of growth joint mobility Physical endurance. 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
25. 25. Surgical care corneal transplantation. correction of nerve entrapments in the hands, heart valve replacement. Correction of the contractures and osteal deformities . For patients with Mucopolysaccharidoses type IV, cervical myelopathy
26. 26. complications Cardiac Respiratory Ocular CNS Musculoskeletal Hearing loss Carpal tunnel syndrome
27. 27. Prevention Primary prevention through genetic counseling Tertiary prevention to avoid or treat the complications Multidisciplinary attention to Respiratory complications Cardiovascular complications Hearing loss Carpal tunnel syndrome Cord compression Hydrocephalus
28. 28. prognosis Progressive nature of clinical involvement in MPS patients dictates the need of specialized, coordinated evaluation and long term follow up Prognosis is generally poor but life expectancy can be improved with management Follow up every 6-12 months