Test Background

Mucopolysaccharidosis type I (MPSI), a lysosomal storage disease, is an autosomal recessive condition caused by alpha-L-iduronidase (IDUA) deficiency resulting in progressive accumulation of partially degraded mucopolysaccharides in the lysosomes. MPSI is a progressive multisystem disorder that constitutes a clinical spectrum ranging in severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes, Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome, there are no biochemical differences and the clinical findings overlap. Therefore, affected individuals are best described as having either severe or attenuated MPS I, which affects therapeutic options. Infants with the severe form appear normal at birth. Early features include umbilical or inguinal hernia, frequent upper respiratory tract infections, and then coarsening of the facial features, which may not become apparent until after one year of age. Gibbus deformity of the lower spine and hearing loss are common. Progressive skeletal dysplasia is always noted leading to growth stagnation by three years of age. Intellectual disability is progressive and profound. Death is typically the result of cardiorespiratory failure, which usually occurs within the first ten years of life. In the attenuated form, the severity and rate of progression range from life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint problems. Onset of features typically occurs between three and ten years of age. While some individuals have no neurologic involvement and normal psychomotor development in early childhood, learning disabilities may develop. Hearing loss and cardiac valvular disease are common. This laboratory performs Sanger sequencing of the IDUA gene.