This document presents a case report of a 3-year-old male child presenting with fever, cough, ear discharge and abdominal distension. On examination, the child had coarse facial features, hepatosplenomegaly, and limited joint mobility. The differential diagnosis included Hurler disease, a type of mucopolysaccharidosis caused by alpha-L-iduronidase deficiency leading to glycosaminoglycan deposition. Testing confirmed Hurler disease. The document then provides details on mucopolysaccharidoses classification, symptoms, management including hematopoietic stem cell transplantation and enzyme replacement therapy, and complications.

2. Clinical Case Presentation
Dr. Safeer Ahmed Jamil
FCPS II Trainee
Pediatrics

3. 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

4. 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

5. 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.

6. Diagnosis/Differentials

7. Hurler Disease
MUCOPOLYSACCHARIDOSES

8. 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

9. 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

10. Rule of fingers
Heparan sulfate
(impaired degradation)
Mental
deficiency
Dermatan sulfate,
Chondroitin sulfates,
Keratan sulfate
(impaired degradation)
Mesenchymal
abnormalities

12. Clinical manifestations ..(MPS)

13. 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

14. 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)

17. 17

18. 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

19. 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

20. MORQUIO DISEASE (MPS IV)
 N-Aetyle-Glactosamine—Sulfatase Defeciency…keraten 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)

22. 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

23. 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

25. 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

26. 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

27. 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.

28. 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

29. 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

30. 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

31. 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

32. complications
Cardiac
Respiratory
Ocular
CNS
Musculoskeletal
Hearing loss
Carpal tunnel syndrome

33. 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

34. 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