Orthopedics - Oleksa A.P. 2006

Joint Pathophysiology
Developmental Defects and Congenital Skeletal Anomalies
Mucopolysaccharidoses

Mucopolysaccharidoses (Table 1) result from lysosomal enzyme deficiencies and are characterized by impaired glycosaminoglycan METABOLISM, leading to their abnormal accumulation within the body. Orthopedic pathology is a hallmark of all types of mucopolysaccharidosis.

Mucopolysaccharidosis Type I (MPS I, Hurler and Scheie syndromes)

Mucopolysaccharidosis Type I is inherited in an autosomal recessive manner and presents with two main clinical phenotypes. Hurler syndrome (MPS I-H) is described first. The primary defect is a deficiency of lysosomal a-L-iduronidase across all fractions. The pathology manifests as an accumulation of mucopolysaccharides in parenchymal and mesenchymal Tissues, along with lipid deposition in neuronal Cells (Jones K.L., 1988). Diagnosis is based on clinical evaluation. Characteristic features include a coarse facies with full Lips, hypertelorism, corneal clouding, Kyphosis, and a thoracolumbar gibbus. Urinalysis reveals dermatan sulfate and heparan sulfate. Fibroblast cultures demonstrate a complete absence of a-L-iduronidase.

Scheie syndrome, or MPS I-S, shares the same enzymatic defect and urinary dermatan sulfate excretion as Hurler syndrome, being differentiated from MPS I-H solely on The basis of Clinical presentation and phenotype. Joint stiffness is typically present, though careful examination may reveal subtle variations.

Mucopolysaccharidosis Type II (MPS II, Hunter syndrome)

Mucopolysaccharidosis Type II is an X-linked recessive disorder. The primary defect is iduronate-2-sulfatase deficiency, resulting in excess dermatan sulfate and heparan sulfate excretion in the urine. Clinical manifestations include coarse facial features, psychiatric disorders, and neurological impairment. The clinical phenotype tends to progress from mild to severe, featuring progressive joint stiffness and The Development of coxarthrosis. Unlike other MPS disorders, children with MPS II present with clear sclerae and a moderately pronounced gibbus; girls may initially appear mildly affected, but these features evolve over time (Jones K.L., 1988).

Mucopolysaccharidosis Type III (MPS III, Sanfilippo syndrome)

Mucopolysaccharidosis Type III was first described in 1963 (Jones K., Sanfilippo S.J. et al.). It is characterized by progressive intellectual disability. Between the ages of one and three years, patients typically experience a steady decline in cognitive and physical Functions. These children become wheelchair-bound at an early age and often struggle to operate wheelchairs independently; many succumb to pulmonary complications between 10 and 20 years of age.

There are four distinct subtypes of this syndrome (A, B, C, D), which are clearly differentiated by their specific enzymatic defects, yet all share identical Clinical Features and urinary excretion of heparan sulfate.

Mucopolysaccharidosis Type IV (MPS IV, Morquio syndrome)

Mucopolysaccharidosis Type IV is inherited in an autosomal recessive manner. The disorder is characterized by prominent orthopedic skeletal deformities in patients with normal intelligence. Type IVA is caused by a deficiency of N-acetylgalactosamine-6-sulfatase. Type IVB is due to a ß-galactosidase deficiency. The diagnosis is confirmed by identifying excessive urinary excretion of keratan sulfate alongside demonstrated enzyme deficiency in cultured Skin fibroblasts or leukocytes (Jones K.L., 1988). Pronounced platyspondyly, Genu Valgum, shortening of the long bones, coxa vara, and corneal clouding are typical generalized features. Odontoid hypoplasia and generalized ligamentous laxity lead to C1-C2 spinal instability and therefore require active management.

Class="center">Table 1. Biochemical defects in saccharidoses (after Frymoyer, 1993)

Mucopolysaccharidosis Type VI (MPS VI, Maroteaux-Lamy syndrome)

This syndrome results from an arylsulfatase B deficiency and is classified into a mild subtype—where children present with Congenital Heart defects—and a severe subtype, characterized by progressive and serious orthopedic deformities manifesting between the ages of 3 and 6 years.

Affected children exhibit certain clinical features reminiscent of Hurler syndrome, but cognitive and intellectual impairment is typically absent. Characteristic findings include joint contractures, thoracolumbar kyphosis with platyspondyly, genu valgum, and odontoid hypoplasia (Maroteaux H., Lamy M.).