QUESTION: Background Your patient is a 2-year-old male infant named Justin N He
ID: 78257 • Letter: Q
Question
QUESTION:
Background Your patient is a 2-year-old male infant named Justin N He is suffering from hypotonia, weakness and growth failure, and is unable to walk. His mother has just brought him into the emergency room from the family beach house, where they have been spending the summer, because he has had a seizure. X-rays indicate that the infant is suffering from rickets, which is a result of a nutritional deficiency of Vitamin D. But the infant's mother insists that her son's diet is not Vitamin D-deficient. He drinks three glasses of milk a day, and his diet also includes meat and eggs. You decide to carry out further analysis and take a sample of the infant's blood. The laboratory results are shown in Table 29.1 Table 29 Laboratory results from a patient with a suspected Vitamin D deficiency. Patient Normal Range Serum calcium, mg/dL 5.1 8.7-10.1 Serum phosphorous, mg/dL 2.4-4.3 4.2 Serum la, 25-dihydroxycholecalciferol, pg/mL 13 20-76 48 Serum 25-hydroxycholecalciferol, ng/mL 10-55 A simplified scheme of Vitamin D metabolism is shown in Figure 29.1. The chemical name of active Vitamin D is la, 25-dihydroxycholecalciferol, and it is synthesized via the pathway shown. Catalysts, both in the form of enzymes and ultraviolet light, are required for Vitamin D synthesis. The two main sources of active Vitamin D are diet and sunlight. Food supplemented with "Vitamin D" usually contains cholecalciferol (Witamin D3), or possibly a biologically equivalent analog. In the liver, dietary cholecalciferol is converted to 25-hydroxycholecalciferol. Next, in the kidney, the 25Explanation / Answer
The enzyme in the kidney which is responsible for the conversion of 25 hydroxycholecalciferol to active vitamin D is non-functional as the precursor of till the stage before is in the normal range within the patient. Amino acid change is from glycine to serine in the patient.
Other patients A: Gly-Glu B: Arg-Pro C: Pro-ser
In order to check whether the enzyme is non-functional, the active vit D formation can be traced in a cultured cell with the expression vector vs without it. The formation of vitamin D will indicate its functional presence in control and in the mutant, its absence would indicate it to be not normal.
Most of the amino acid changes which have been seen are actually leading to a major change in charge which in turn would affect the conformation of the enzyme and thus would render the enzyme non-functional.