A family suspected of child abuse because one of their children has had multiple fractures consults an ohopedic specialist at a children's hospital. The specialist examines the child, who is now 5 years old, and notes that the child has blue-tinged sclera, hearing loss, and small, slightly blue, misshapen teeth. Radiologic studies confirm the presence of numerous fractures of various ages. No significant degree of bruising is seen over sites of recent fracture. The disease this child most likely has is related to abnormal metabolism involving which of the following substances?
The suspected disease is osteogenesis imperfecta, which is a rare genetic disorder that occurs in both recessive and dominant forms. The clinical presentation, depending on the specific form, varies from death in utero, to that described in the question stem, to very mild disease with only a modest increase in bone fragility. The different types all have defects in the synthesis of type I collagen, often with insufficient or abnormal pro-a1(1) or pro-a2(1) chains. These deficits produce an unstable collagen triple helix that is not as strong as normal collagen.Defective glycogen metabolism is associated with the various glycogen storage diseases, such as von Gierke disease and Pompe disease. These diseases tend to present with profound hypoglycemia, hepatomegaly, or muscle weakness.Defective mucopolysaccharide metabolism is associated with the mucopolysaccharidoses, such as Hurler and Hunter syndromes. These diseases tend to present with abnormal facies ("gargoylism"), deformed ("gibbus") back, claw hand, and stiff joints.Abnormalities of purine metabolism are present in gout, which presents with joint inflammation and often involves the great toe. Ref: Wyatt C., Butterwoh IV J.F., Moos P.J., Mackey D.C., Brown T.G. (2008). Chapter 19. Pathology of the Bones and Joints. In C. Wyatt, J.F. Butterwoh IV, P.J. Moos, D.C. Mackey, T.G. Brown (Eds), Pathology: The Big Picture.
Collagen
Glycogen
Mucopolysaccharides
Purines