eMedicine Specialties > Pediatrics: General Medicine > Hematology
Pearson Syndrome
Updated: Jul 31, 2007
Introduction
Background
In 1979, Pearson et al described a previously unrecognized, often fatal disorder of infants with transfusion-dependent sideroblastic anemia, vacuolization of hematopoietic precursors, and exocrine pancreatic insufficiency. The large deletions of the mitochondrial genome that cause the disorder were discovered a decade later.
Pearson syndrome is currently recognized as a rare, multisystemic, mitochondrial cytopathy. Its features are refractory sideroblastic anemia, pancytopenia, defective oxidative phosphorylation, exocrine pancreatic insufficiency, and variable hepatic, renal, and endocrine failure. Death often occurs in infancy or early childhood due to infection or metabolic crisis. Patients may recover from the refractory anemia. Older survivors have Kearns-Sayre syndrome (KSS), which is a mitochondropathy characterized by progressive external ophthalmoplegia and weakness of skeletal muscle.
Pathophysiology
Mitochondropathies
The mitochondropathies comprise several diverse, overlapping syndromes caused by mutations of mitochondrial DNA. Pearson syndrome is a specific clinical subset of these syndromes that 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. Abnormal metabolism of iron, evidenced by sideroblastosis and hemosiderosis, may also be a key feature (see Image 3). 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.
Defining features of Pearson syndrome
The first defining feature of Pearson syndrome is marrow failure. Macrocytic sideroblastic anemia occurs with the characteristic vacuolation of hematopoietic precursors (see Images 1-2). The anemia is refractory, and patients may be transfusion dependent. Neutropenia and thrombocytopenia may also be present.
The second defining feature of Pearson syndrome is dysfunction of the exocrine pancreas due to fibrosis and acinar atrophy. The result is malabsorption and chronic diarrhea.
Another cardinal feature of Pearson syndrome is persistent or intermittent lactic acidemia, which is caused by a defect in oxidative phosphorylation.
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, are relatively uncommon. The endocrine pancreas usually remains functional; however, a few patients develop diabetes mellitus. Splenic atrophy and impaired cardiac function have also been reported.
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, and, perhaps, concomitant endocrinologic abnormalities.
Frequency
United States
Pearson syndrome is rare. Approximately 60 cases have been reported worldwide.
International
See United States.
Mortality/Morbidity
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.
Race
All races can be affected.
Sex
Pearson syndrome has no sex predilection.
Age
Pearson syndrome is a progressive disease, and its features change with age. Neonates may be well at birth, but some neonates with Pearson syndrome have low birth weight, pallor, and anemia. 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, 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 due 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.
Clinical
History
- Although the history is nonspecific, the astute clinician recognizes the need for further evaluation.
- Parents and/or caregivers may notice that the infant has been pale since birth, perhaps increasingly so; this finding indicates refractory anemia.
- Chronic diarrhea and fatty stools may be reported and indicate pancreatic exocrine deficiency.
- Inquire about previous illnesses or hospitalizations. Episodes of anorexia, vomiting, fever, and lethargy can occur. Associated dehydration, electrolytic abnormalities, lactic acidosis, and hepatic dysfunction may occur.
- Inquire about weight and obtain a growth chart. The birth weight may have been low, and the infant may fail to gain weight.
- A dietary history is important because deficiencies of copper, riboflavin, and phenylalanine may cause anemia with vacuolization of hematopoietic precursors, similar to changes observed in Pearson syndrome.
- Obtain a history of exposure to drugs. Certain drugs can damage the bone marrow. For example, chloramphenicol can cause sideroblastic changes and vacuolization of hematopoietic precursors, similar to its effects in individuals with Pearson syndrome.
- Obtain a family history.
- Some anemias and syndromes of bone marrow failure, such as X-linked sideroblastic anemia and Diamond-Blackfan anemia, affect families. A good family history can alert the clinician to these possible diagnoses.
- Although mitochondropathies can be inherited maternally, Pearson syndrome appears to be sporadic.
Physical
- No pathognomonic physical characteristics are observed.
- Anemia causes pallor.
- The patient's weight may be low for his or her age, and some patients are cachectic.
- Hepatomegaly, often progressive, occurs in patients with hepatic involvement.
- Patchy erythema and photosensitivity are also reported.
- Examine the patient for anomalies associated with other syndromes of bone marrow failure that present in the neonate or infant. For example, anomalies of the radii and thumb suggest Fanconi anemia, Diamond-Blackfan anemia, or the thrombocytopenia-absent radii syndrome.
Causes
Several types of abnormalities of mitochondrial DNA cause Pearson syndrome.
More on Pearson Syndrome |
 Overview: Pearson Syndrome |
| Differential Diagnoses & Workup: Pearson Syndrome |
| Treatment & Medication: Pearson Syndrome |
| Follow-up: Pearson Syndrome |
| Multimedia: Pearson Syndrome |
| References |
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References
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Cormier V, Rotig A, Quartino AR, et al. Widespread multi-tissue deletions of the mitochondrial genome in the Pearson marrow-pancreas syndrome. J Pediatr. Oct 1990;117(4):599-602. [Medline].
De Vivo DC. The expanding clinical spectrum of mitochondrial diseases. Brain Dev. Jan-Feb 1993;15(1):1-22. [Medline].
Gibson KM, Bennett MJ, Mize CE, et al. 3-Methylglutaconic aciduria associated with Pearson syndrome and respiratory chain defects. J Pediatr. Dec 1992;121(6):940-2. [Medline].
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Pearson HA, Lobel JS, Kocoshis SA, et al. A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction. J Pediatr. Dec 1979;95(6):976-84. [Medline].
Rotig A, Bourgeron T, Chretien D, et al. Spectrum of mitochondrial DNA rearrangements in the Pearson marrow-pancreas syndrome. Hum Mol Genet. Aug 1995;4(8):1327-30. [Medline].
Rötig A, Cormier V, Blanche S, et al. Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J Clin Invest. Nov 1990;86(5):1601-8. [Medline].
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Seneca S, De Meirleir L, De Schepper J, et al. Pearson marrow pancreas syndrome: a molecular study and clinical management. Clin Genet. May 1997;51(5):338-42. [Medline].
Stacpoole PW, Kerr DS, Barnes C, et al. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics. May 2006;117(5):1519-31. [Medline].
Stoddard RA, McCurnin DC, Shultenover SJ, et al. Syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction presenting in the neonate. J Pediatr. Aug 1981;99(2):259-61. [Medline].
Superti-Furga A, Schoenle E, Tuchschmid P, et al. Pearson bone marrow-pancreas syndrome with insulin-dependent diabetes, progressive renal tubulopathy, organic aciduria and elevated fetal haemoglobin caused by deletion and duplication of mitochondrial DNA. Eur J Pediatr. Jan 1993;152(1):44-50. [Medline].
Further Reading
Keywords
Pearson syndrome, Pearson's syndrome, Pearson marrow-pancreas syndrome, Online Mendelian Inheritance in Man #557000, OMIM #557000, sideroblastic anemia with marrow cell vacuolization and exocrine pancreatic dysfunction, pancytopenia, defective oxidative phosphorylation, exocrine pancreatic insufficiency, Kearns-Sayre syndrome, KSS, marrow failure, Fanconi syndrome, Fanconi's syndrome, Fanconi anemia, Fanconi's anemia, FA, Diamond-Blackfan anemia, DBA, macrocytic anemia
