Chapter 32: Nitrogen: Nucleotide Metabolism
You are treating a 4-year-old child who has been afflicted with recurrent infections. The child exhibits retarded development, weakness, and weight loss. Physical examination also shows absent tonsils and blood work reveals a lack of lymphocytes. These signs and symptoms are due to which of the following disorders?
B. Kelley-Seegmiller syndrome
E. severe-combined immunodeficiency (SCID)
Answer E: SCID usually presents within the first month of life with failure to thrive and life-threatening interstitial pneumonitis. The gastrointestinal tract as well as the skin is also frequently involved in initial infections. Candidiasis is first observed as “diaper rash” but then progresses to an extensive infection involving the skin, oral and esophageal mucosa, and the vagina. Persistent infections prompt most parents to have their baby examined and SCID is thus often diagnosed by 1 to 2 months of age from a determination of immune function. Most SCID patients lack both cell-mediated (T cell) and humoral (B cell) immunity, thus the derivation of the disease name: severe combined immunodeficiency.
You are examining a 7-year-old male child who exhibits delayed motor development, overexaggerated reflexes, and spasticity. In addition, the boy has a tendency to chew his lips and fingers often causing tissue damage and bleeding and has painful, swollen, and inflamed joints. The most likely diagnosis in this case is Lesch-Nyhan syndrome. Analysis of blood from this patient would be expected to find elevated levels of which of the following compounds related to the observed findings?
Answer E: Lesch-Nyhan syndrome results from deficiencies in hypoxanthine-guanine phosphoribosyltransferase (HGPRT). HGPRT is a purine nucleotide salvage enzyme that converts guanine to GMP and hypoxanthine to IMP. Loss of this salvage enzyme results in increased rates of purine nucleotide catabolism whose end product is uric acid.
You are examining a 5-year-old male child who has been exhibiting a tendency to bite his lower lip to the point of bleeding as well as chewing on his fingertips. Physical examination demonstrates swollen tender joints, and blood workup indicates elevated uric acid levels. These symptoms and lab results are indicative of a deficiency in which of the following enzymes?