The association between haematological manifestation and mtDNA deletions in Pearson syndrome

Abstract

We studied the proportion of deleted mitochondrial DNA in blood cells from patients with Pearson syndrome. Patient 1 is a 17-year-old female with Kearns-Sayre syndrome who survived Pearson syndrome. Patient 2 is a 5-year-old boy with Pearson syndrome who recovered from refractory anaemia but continues to have thrombocytopenia and neutropenia. Patient 3 is a female neonate who died with severe acidosis and pancytopenia at 14 days of age. Southern blot analysis was performed with total DNA from three patients' blood cells and two samples of bone marrow cells from one patient. In peripheral blood, patients with a higher proportion of deleted mitochondrial DNA had lower blood cell counts. In patient 2, the percentage of mutant mitochondrial DNA in bone marrow cells decreased as anaemia improved. This indicates that the proportion of deleted mitochondrial DNA in peripheral blood and in bone marrow has a tendency to correlate to the severity of haematological manifestation.

Reversible infantile respiratory chain deficiency: A clinical and molecular study

“…For mtDNA analysis, total DNA was extracted from muscle specimens of 6 patients (patients 1–6) and lymphocytes of patients 7 and 8. Southern blot and long polymerase chain reaction (PCR) analyses were performed to detect mtDNA rearrangements, as described previously 22, 23. Total mtDNA sequencing was performed as described previously 24.…”

Hematological Manifestations of Primary Mitochondrial Disorders

“…PS is characterized by iron-refractory, transfusion-dependent sideroblastic anemia, aplastic anemia [20], megaloblastic anemia, leukopenia, neutropenia, thrombocytopenia, or pancytopenia and exocrine pancreatic dysfunction (table 4) [21,22,23]. Additional clinical features include failure to thrive, villous atrophy with chronic diarrhea, lactic acidosis, muscle hypotonia, pancreas dysfunction, and ataxia [23, 24].…”

“…Different phenotypic expression of the common deletion in relatives may be due to developmentally regulated tissue-specific nuclear factors [29]. There are indications that the blood cell count decreases with an increasing percentage of mutant mtDNA [21]. Conversely, it has been shown that the proportion of deleted mtDNA in bone marrow cells decreased as anemia improved [21].…”

“…Conversely, it has been shown that the proportion of deleted mtDNA in bone marrow cells decreased as anemia improved [21]. The proportion of deleted mtDNA in bone marrow cells correlates with the severity of the hematological manifestations [21]. …”

Bone marrow features in Pearson syndrome with neonatal onset: A case report and review of the literature

“…Fifty percent of affected children die in infancy because of bone marrow (BM) failure, infections, metabolic acidosis, or kidney insufficiency. In children who survive, a spontaneous hematologic improvement is noted in almost all cases, and in one of three cases a phenotypic transformation to Kearns–Sayre syndrome or Leigh syndrome is observed later in life . The presence of vacuolization in myeloid and erythroid progenitors on BM aspirate (BMA) is suggestive of PS.…”