Mitochondrial DNA deletion syndromes (Pearson, Kearns-Sayre, CPEO)
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An infant with refractory sideroblastic anemia and pancreatic insufficiency (Pearson) later develops ptosis, ophthalmoplegia, and cardiac conduction defects (Kearns-Sayre).
Sporadic; large single mtDNA deletions (usually 2-10 kb)
- Same deletion can cause different phenotypes depending on tissue distribution
Phenotypic Spectrum:
| Syndrome | Onset | Key Features |
|---|---|---|
| Pearson | Infancy | Sideroblastic anemia, pancreatic insufficiency, lactic acidosis |
| Kearns-Sayre | <20 years | PEO, pigmentary retinopathy, cardiac conduction defects |
| CPEO | Adulthood | Progressive external ophthalmoplegia, ptosis |
- Pearson survivors often evolve to Kearns-Sayre phenotype
- Cardiac monitoring essential (risk of sudden death from heart block)
- Sporadic (de novo deletions); low recurrence risk
- mtDNA deletion analysis (long-range PCR, Southern blot, or quantitative methods); higher deletion load in affected tissue (muscle) than blood
- Kearns-Sayre triad: onset <20 years, PEO, and pigmentary retinopathy, plus one of cardiac conduction block, CSF protein >100 mg/dL, or cerebellar ataxia
- Muscle biopsy: ragged red fibers, COX-negative fibers
- Elevated lactate (serum and CSF)
- Cardiac surveillance with serial ECG; pacemaker for conduction block (prevents sudden death in Kearns-Sayre)
- Pearson syndrome: transfusion support for anemia and pancreatic enzyme replacement for exocrine insufficiency
- Ophthalmology, audiology, and endocrine monitoring; ptosis surgery as needed
- Avoid mitochondrial toxins; genetic counseling (sporadic, low recurrence risk)
"PKP" = Pearson, KSS, PEO: the three phenotypes caused by single mtDNA deletions, from earliest to latest onset. "PeaK Power" or "PicKuP truck." Rotate the "d" in "deletion" to get a "P."
"PearSon" = Pancreas + "Sytopenia": Pearson syndrome has pancreatic insufficiency and bone marrow failure (sideroblastic anemia). Pearson survivors evolve to Kearns-Sayre.
Kearns-Sayre has "Kardiac Syncope": may need pacemaker due to AV block (conduction defect). "K5 deletion": the common 4,977 bp deletion is ~5 kb ("Kearns 5ayre = Sayonara to the 5 kb region"). For KSS, check Kalcium and EKG (Konduction).