Disorders: SCID, Orotic Aciduria
Start with the big picture
In ADA-deficient SCID, deoxyadenosine and dATP accumulate; excess dATP inhibits ribonucleotide reductase, reducing DNA synthesis and impairing T- and B-cell development. The result is severe immunodeficiency, often presenting in infancy. PNP deficiency is a rarer purine salvage defect associated mainly with T-cell immunodeficiency and neurologic signs. Orotic aciduria results from deficient UMP synthase activity in de novo pyrimidine synthesis, limiting UMP production. Its characteristic findings include megaloblastic anemia that does not respond to folate or vitamin B12, growth retardation, and urinary orotic acid. Normal ammonia helps distinguish it from OTC deficiency, where ammonia is elevated. The deeper lesson connects these mechanisms to diagnostic features and management approaches, including uridine replacement for orotic aciduria and therapies for ADA-deficient SCID.
What you'll learn
- Explain how ADA deficiency leads to impaired DNA synthesis and combined immunodeficiency.
- Distinguish the main features of ADA- and PNP-deficient SCID.
- Describe the enzyme defect and nucleotide consequences of orotic aciduria.
- Differentiate orotic aciduria from OTC deficiency using ammonia findings.
- Identify the management approaches described for these disorders.
Continue your study
Work through the complete notes and reinforce the topic with the study tools available in the full lesson.
