High-Yield Facts from Kaplan

Question 1

The deficiency of which enzyme is a major cause of SCID (autosomal recessive)? What is the pathogenesis?

Answer 1

• adenosine deaminase deficiency in the purine salvage pathway
• excess ATP/dATP –> feedback inhibition of ribonucleotide reductase in pyrimidine base production –> inhibition of DNA synthesis –> decreased lymphocyte count

Question 2

A five-year-old boy is brought in with signs of dystonia, mental retardation, and aggression. During physical exam you find that he is missing several fingers and toes. Blood test shows high uric acid levels. Synovial fluid from an affected joint shows needle-like crystals with negative birefringence under polarized light. What enzyme deficiency does this boy have? What is the treatment?

Answer 2

• lacks HGPRT in the purine salvage pathway (converts hypoxanthine –> IMP and guanine –> GMP)
• excessive uric acid production and de novo purine synthesis
• inheritance is X-linked recessive
• Tx is allopurinol or febuxostat (2nd line xanthine oxidase inhibitor)

Question 3

A 9-month-old female infant presented with failure to thrive, repeated respiratory infections, and megaloblastic anemia refractory to administration of cobalamin, pyridoxine, folic acid, and iron. Urinalysis demonstrated a crystalline sediment and a blood test showed normal ammonia levels. Which of the following pathways is defective in this infant?

Answer 3

• defective UMP synthase in de novo pyrimidine synthesis –> orotic acid not covered to UMP –> orotic acuduria
• lack of pyrimidine bases –> less DNA replication