summary Mucopolysaccharidoses are a group of 13 metabolic syndromes caused by the absence or malfunctioning of lysosomal enzymes which break down glycosaminoglycans. Patients present with proportionate dwarfism, atlantoaxial instability, increased rate of carpal tunnel syndrome, cardiac abnormalities, mental retardation, and facial abnormalities. Diagnosis is made with urine tests to analyze the excess mucopolysaccharides, skin fibroblast culture to test enzyme activity, and intra-uterine chorionic villous sampling. Treatment involves a multidisciplinary approach to improve and maintain function. Bone marrow transplantation improves life expectancy, but does not alter orthopaedic manifestations. Etiology Main forms include Morquio syndrome and Sanfilippo syndrome most common Hurler syndrome Hunter syndrome Pathophysiology lysosomal storage disorders due to incomplete glycosaminoglycan breakdown products (mucopolysaccharides) accumulating and causing dysfunction in various organs glycosaminoglycans are long sugar carbohydrate chains that help build bone, cartilage, tendons, corneas, skin and connective tissue Associated conditions orthopaedic manifestations proportionate dwarfism increased rate of carpal tunnel syndrome C1-C2 instability delayed hip dysplasia abnormal epiphyses bullet-shaped phalanges genu valgum nonorthopaedic conditions complex sugars in the urine visceromegaly corneal clouding cardiac disease deafness mental retardation (except Morquio syndrome) enlarged skull Studies Labs urine test (toluidine blue-spot test) to analyze the excess mucopolysaccharides skin fibroblast culture to test enzyme activity chorionic villous sampling Morquio Syndrome Characterized by accumulation of keratan sulfate interferes with the cartilage at the growth plate presents at 18-24 months Pathophysiology Type A (galactosamine-6-sulfate-sulphatase deficiency) Type B (beta-galactosidase deficiency) Genetics autosomal recessive Prognosis Type A is more severe Type A and B survive into adulthood Presentation proportionate dwarfism normal intelligence waddling gait genu valgum thoracic kyphosis corneal clouding Radiographs thickened skull wide ribs vertebral beaking coxa vara with unossified femoral head bullet-shaped metacarpals odontoid hypoplasia leading to cervical instability (obtain flexion-extension x-rays) thoracic kyphosis with platyspondia Studies keratan sulfate in urine Treatment decompression and cervical fusion indications myelopathy with C1-C2 instability realignment osteotomies restores plumb alignment to limb malalignment commonly recurs guided growth attractive alternative to osteotomies, but there is a lack of evidence Hurler Syndrome (Gargoylism) The most severe mucopolysaccharidosis Pathophysiology caused by alpha-L iduronidase deficiency leads to accumulation of dermatan sulfate Genetics inheritance pattern autosomal recessive Prognosis death in first decade of life Presentation physical exam proportionate dwarfism progressive mental retardation cloudy corneas genu valgum C1-C2 instability (25%) carpal tunnel syndrome and finger triggering Studies dermatan sulfate in the urine Treatment bone marrow transplantation indications in performed 1st year of life extend lifespan but it doesn't change phenotypic orthopaedic changes San Filippo Syndrome characterized by accumulation of heparan sulfate Pathophysiology multiple enzyme deficiencies Genetics autosomal recessive Prognosis death in second decade of life Presentation mental retardation proportionate dwarfism clear cornea Studies heparan sulfate in the urine Treatment bone marrow transplant has increased lifespan Hunter Syndrome Pathophysiology sulpho-iduronate-sulphatase deficiency leads to accumulation of dermatan/heparan sulfate Genetics X-linked recessive Prognosis death by 2nd decade of life Presentation mental retardation proportionate dwarfism clear cornea Studies dermatan/heparan sulfate in urine Prognosis Bone marrow transplant improves life expectancy, but doesn't alter orthopaedic manifestations