CASE 3 A 9 month old female is brought to the pediatric clinic because of listlessness and anorexia.

She is the daughter of an unemployed poor urban couple and has never before seen a pediatrician or taken any medication. Her parents report a diet of unsupplemented cows milk. Physical examination reveals weakness, pallor, hyperkeratosis and hemorrhagic perifolliculitis of the skin of the lower extremities, forearms, and abdomen. There are purpuric skin rashes, splinter hemorrhages in the nail beds of the hands, tenderness and swelling of the distal femur and costochondral junctions. There are bleeding gums, and petechiae are seen over the nasal and oral mucosa. The CBC reveals microcytic, hypochromic anemia, and leukopenia. Plasma and platelet levels of ascorbic acid are low. The bleeding time is prolonged. X-rays show subperiosteal hemorrhages, both legs and knees show ground glass appearance of bones and epiphyses. QUESTIONS 1. What is the most likely diagnosis? Justify your answer. Diagnosis: Scurvy / Ascorbic Acid Deficiency / Vitamin C Deficiency Justification: Vitamin C (Ascorbic Acid) deficiency, or scurvy, is observed in smokers, oncologic patients, alcoholic, the elderly, and in this case infants because of impaired collagen synthesis. Since collagen is involved in the synthesis of epithelial and connective tissues in different parts of the body particularly in epithelial tissues in the gums/teeth and blood vessels. Deficiency of this may explain the following manifestations: hemorrhagic perifolliculitis, purpuric skin rashes, splinter hemorrhages, bleeding gums, petechiae, and subperiosteal hemorrhages.

2. Explain the biochemical basis of the patients condition. Vitamin C is essential for collagen formation. It is water-soluble and it helps in iron absorption and transport and it participates in tyrosine metabolism. In addition to it being an important biological antioxidant, ascorbic acid is required for the hydroxylation of proline and lysine residues of procollagen in collagen synthesis. These hydroxylation reactions require molecular oxygen, Fe 2+, and the reducing agent vitamin C, without which the hydroxylating enzymes prolyl hydroxylase and lysyl hydroxylase are unable to function. In the case of ascorbic acid deficiency, interchain H-bond formation is impaired, as is formation of a stable triple helix. Additionnally, collagen fibrils cannot be cross-linked, greatly decreasing the tensile strength of the assembled fiber. The resulting deficiency disease is scurvy. Patients with ascorbic acid deficiency often show bruises on the limbs as a result of subcutaneous extravasation of blood due to capillary fragility. Treatment may include oral ascorbic acid (high doses of which may produce oxalate and uric acid stones).