PM1045: Cardiac Manifestations of Pearson Syndrome

Background: Pearson syndrome is a rare mitochondrial disorder with many multi-system manifestations. There is scarce data about the natural history of cardiac disease in this patient population. We sought to describe the rhythm abnormalities and cardiac dysfunction in this group.

Methods: Patients enrolled in the prospective NIH Clinical Trial titled ' Natural History of Pearson Syndrome' (Record locator NCT02327364) from March 2014 to October 2021 were included in this retrospective study. All patients had a confirmed diagnosis of Pearson Syndrome which required a large scale mtDNA deletion along with sideroblastic anemia.

Results: A total of 16 patients met inclusion criteria of which 3 had incomplete data. Of the 13 patients who were included, 9 (69%) were males and the median age of presentation was 3 months (IQR 3-5 mos). The median follow up from diagnosis was 7.1 yrs (range 0.4-18.5 yrs). 6 patients had conduction defects with all 6 (100%) requiring pacemaker implantation; the indications were 2nd degree type 2 block in 4 patients, complete heart block (CHB) and complete right bundle branch block (BBB) in 1 patient each (Figure 1). The median age at pacemaker implantation was 10 years (IQR 7.8-11.3 yrs). All patients had progression of conduction defect from BBB to either 2nd degree type 2 or CHB within a median of 11 months (IQR 4-18 mos) (Figure 2). The shortest time to progression from bundle branch block to advanced heart block was 3 months and presented with severe symptomatic bradycardia in 1 patient. 2 patients developed decreased left ventricle ejection fraction (24% and 53%) starting at a mean age of 14.6 yrs (Range 14.3 - 14.9 yrs). Both these patients had pacemaker implanted at a mean of 2.7 yrs (range 1.2-4.2 yrs) prior to the development of ventricular dysfunction and were paced >50% of the time at their last visit. All patients with conduction defects had evolution to Kearns Sayre Syndrome.

Conclusion: Early signs of conduction defect progressed quickly and required pacemaker implantation in 6 patients (46%) in our study population. Similar to other mitochondrial disorders where rapid progression of conduction defects is well known, our patient population demonstrated a parallel pattern. This data suggests that pacemaker implantation at the onset of conduction disease is indicated.