1. MUCOPOLYSACCHARIDOSIS-MPS
Dr. NZIOKI CM
CONSULTANT ENDOCRINOLOGIST
MACHAKOS LEVEL 5 HOSPITAL

2. Outline Introduction Mode of inheritance Classification
Clinical presentation
Diagnosis
Management of MPS

3. INTRODUCTION
Mucopolysaccharidosis (MPS) are hereditary progressive disorders caused by defective catabolism of sulfated components of connective tissue- glycosaminoglycans (GAG’s)
The major GAGs are:-
dermatan sulfate (DS)
heparan sulfate(HS)
keratan sulfate(KS)
Chondroitin -4- sulfate
Hyaluronan

4. Introduction conti’
Enzymes associated with GAG catabolism are lysosomal hydrolases
Patients with MPS have less than 1%residual enzyme activity
GAGs accumulate in lysosomes – this results in cellular dysfunction and clinical abnormality

6. MPS Classification

7. MPS Classification
Four broad categories based on dominant clinical features
Soft tissue storage and skeletal disease with or without brain disease (MPS I, II, VII)
Soft tissue and skeletal disease(MPS VI)
Primary skeletal disorders (MPS IVA , IVB)
Primary central nervous system disorders ( MPS III A-D)

8. Clinical presentation
Many physical disorders
Varying degree of severity depending on MPS type
Features may not be apparent at birth but progress as storage of GAGs increase

9. Common presentations
CNS disease – mental retardation , developmental delay , severe behavioral problems , hydrocephalus
CVS disease- Valvular dysfunction
Pulmonary disease- airway obstruction, sleep apnoea
Opthalmologic – corneal clouding
Hearing impairment – deafness
Musculoskeletal disease- short stature, joint stiffness
Others – coarse facial features , hepatosplenomegally , hernia

10. Hurler , Hurler-Scheie, Scheie syndrome(MPS I)
Autosomal recessive mode of inheritance
Due to lysosomal α-L- Idoronidase deficiency
Newborns are normal at birth
Clinical features start manifesting by age 1 year

11. Clinical features Developmental delay Coarse thick facial features
Low nasal bridge
Prominent dark eye brows
Progressive joint stiffness
Severe mental retardation

16. Diagnosis
High index of suspicion- a child with coarse facial features, bone disease, developmental delay,short stature, hepatosplenomegally , corneal clouding
GAG urinary concentration
Lysosomal Enzyme assay – definitive diagnosis from cultured fibroblasts,leukocytes
Prenatal diagnosis in selected family clusters- amniocytes and chorionic villus culture

18. Management of MPS
Goal- to reduce severity of symptoms and improve quality of life
Multidisciplinary team care
Neurologist
Pediatrician
Cardiologist
Ophthalmologist
Audiologist
Orthopedic surgeon
Physical and occupational therapist

19. Management Supportive care especially physical therapy is critical
Main treatment modalities are
Haematopoietic stem cell (peripheral blood leukocytes) transplant (HSCT) for MPS I and II.
Has high risk of morbidity and mortality from cardiac and pulmonary complications.
Reduces clinical progression of some features in some children
Enzyme replacement therapy (ERT)- MPS I, II, VI
Treatment results in improvement of somatic disease

20. Thank you
Asanteni

21. Reference
Joseph Muenzer. Overview of the mucopolysaccharidosis, , Rheumatology, Vol 50, 2011
Thomas J et al. Diagnosis of mucopolysaccharidosis, Rheumatology , Vol.50, 2011
Lone Clark. Mucopolysaccharidosis type 1. Gene reviews 2016