Pearson marrow–pancreas syndrome (OMIM #557000) is an uncommon, heterogeneous disorder caused by deletions or duplications of mitochondrial DNA (mtDNA). First reported in 1979, this disorder presents in neonates or infants and is characterized by refractory sideroblastic anemia with vacuolization of marrow precursors, exocrine pancreatic dysfunction, and metabolic acidosis. Consequent multisystem mitochondrial cytopathy results in inadequate ATP generation for cellular energy requirements and secondary accumulation of iron in mitochondria.

Clinical and laboratory manifestations

Pearson syndrome causes multiple abnormalities that are evident in neonates or infants. Anemia, usually macrocytic, was present in 82% of 55 patients. Typical values of hematocrit are 15%–18%. Some patients have neutropenia or thrombocytopenia. The bone marrow is either normocellular or hypocellular. Ringed sideroblasts are present, and there is vacuolization of marrow erythroblasts and delayed erythroid maturation. Some patients develop splenic atrophy.

Pancreatic exocrine insufficiency was observed in 31% of 55 patients before age 4 years. This results in malabsorption, and thus fat is present in stools. The presence of persistent metabolic (lactic) acidosis suggests that affected patients have a mitochondrial disorder. 3-Methylglutaconic aciduria may be a useful marker for Pearson syndrome. Muscle biopsy may reveal ragged-red fibers that lack cytochrome C, an indicator of abnormal function of the respiratory chain that is typically due to deletions or duplications of mtDNA. Neuroimaging in some patients with Pearson syndrome reveals increased signal intensity over the basal ganglia, brainstem, cerebral hemispheres, or vermis. This is attributed to increased mitochondrial iron retention in these areas of the brain.