Pearson marrow-pancreas syndrome, an often fatal disorder, was first described in 1979, by pediatric hematologist/oncologist Howard Pearson. Affected infants manifest a refractory, transfusion-dependent sideroblastic anemia, vacuolization of hematopoietic precursors, and exocrine pancreatic insufficiency.  The last, although frequently encountered, may be absent in some cases of Pearson syndrome. The condition is now known to be a rare, multisystemic, mitochondrial cytopathy with anemia, neutropenia, and thrombocytopenia, as well as variable hepatic, renal, and endocrine failure. Death usually occurs early in life (before age 4 years). The most common causes of death are lactic acidemia (which may be triggered by infection) and liver or renal failure.  Survivors after early childhood develop features of Kearns-Sayre syndrome (KSS), a mitochondropathy characterized by progressive external ophthalmoplegia, weakness of skeletal muscle, atypical retinal pigmentation, and cardiac conduction defects.
The syndrome is due to mitochondrial DNA (mtDNA) deletions of variable size and location; mtDNA encodes for 13 of the respiratory chain enzymes, along with 24 RNA molecules used in intramitrochondrial protein synthesis. As a result, defective oxidative phosphorylation, as well as other defects (occurring in enzymes and RNA molecules), is involved in the syndrome's etiology. Patients may recover from the refractory anemia.
The mitochondropathies comprise several diverse, overlapping syndromes caused by mutations of mitochondrial DNA. Pearson syndrome is a specific clinical subset of these syndromes in which involvement of the bone marrow and exocrine pancreas is prominent. The pathogenesis of Pearson syndrome is complex and not well understood. Deletions of certain components of the electron transport chain, encoded by mitochondrial DNA, cause a defect in cellular oxidative metabolism. Certain transfer RNAs (tRNAs) may also be deleted, and their deletion impairs the translation of messenger RNAs (mRNAs) to proteins.
These defects cause cellular injury in target tissues.
Other mitochondropathies, such as KSS and the mitochondrial myopathies, have deletions of mitochondrial DNA that may be similar or identical to those detected in Pearson syndrome. How similar abnormalities of mitochondrial DNA cause such diverse disorders is not well understood. The distinct phenotypes are probably the result of differences in the amount and in the tissue-specific distribution of abnormal mitochondrial DNA, the evolution of this distribution over time, and the effects of tissue-specific nuclear modifier genes. [7, 8]
Defining features of Pearson syndrome
The first defining feature of Pearson syndrome is marrow failure. Sideroblastic anemia, usually macrocytic and frequently transfusion dependent, is observed in isolation or associated with neutropenia and thrombocytopenia. Bone marrow examination is hypoplastic with characteristic vacuolation of hematopoietic precursors and ringed sideroblasts (see the images below).
The second defining feature of Pearson syndrome is dysfunction of the exocrine pancreas due to fibrosis and acinar atrophy. The result is malabsorption, chronic diarrhea, and poor growth or failure to thrive.
Another cardinal feature of Pearson syndrome is persistent or intermittent lactic acidemia, which is caused by defects in oxidative phosphorylation. Increased lactate/pyruvate ratio is observed along with increased urinary excretion of lactate and related organic acids.
Other organ systems are affected in various ways. Hepatic involvement may cause increases in transaminase, bilirubin, and lipid levels, as well as in steatosis. Some patients develop hepatic failure. Renal involvement is common and manifests as a tubulopathy, such as Fanconi syndrome. Endocrinologic disturbances, such as growth hormone deficiency, hypothyroidism, and hypoparathyroidism, may develop but are not usually part of the initial presentation.  The endocrine pancreas usually remains functional; however, a few patients develop diabetes mellitus and adrenal insufficiency. Splenic atrophy and impaired cardiac function have also been reported. [10, 11, 12, 13, 14]
Failure to thrive is common. Several factors are likely contributory. Such factors include a defect in cellular metabolic energy, malabsorption due to exocrine pancreatic failure, hepatic and renal insufficiency, abnormal myelinization, and possibly endocrinologic abnormalities. [15, 16]
Pearson syndrome is rare. Less than 100 cases have been reported worldwide.
See United States.
Pearson syndrome is often fatal in infancy or early childhood. The usual causes of death are bacterial sepsis due to neutropenia, metabolic crisis, and hepatic failure.
All races can be affected.
Pearson syndrome has no sex predilection.
Pearson syndrome is a progressive disease, and its features change with age. Neonates may be well at birth, but some 40% of patients present in the first year with persistent hypoplastic anemia, other cytopenias, low birth weight, microcephaly, and multiple organ system involvement (GI, neuromuscular, and metabolic). [15, 17, 18] Hydrops fetalis has also been reported. Anemic newborns may need transfusion.
During infancy and early childhood, failure to thrive, chronic diarrhea, and progressive hepatomegaly often occur in individuals with Pearson syndrome. These conditions are punctuated by episodic crises characterized by somnolence, vomiting, electrolytic abnormalities, lactic acidosis (elevated lactate:pyruvate ratio), and hepatic insufficiency. The lactic acidosis may become persistent with time. Typical causes of death in infants and young children with Pearson syndrome are metabolic crisis, hepatic failure, and overwhelming sepsis related to neutropenia.
Some patients survive infancy and early childhood and spontaneously recover from the hematologic dysfunction. Case reports document a shift in the phenotype of these individuals to a predominantly myopathic or encephalopathic condition. For example, some patients who survive early childhood may develop KSS or Leigh syndrome, whereas others may be neurologically healthy.