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

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

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

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

MPS Classification

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)

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

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

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

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

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

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

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

Thank you Asanteni

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