History
The history is nonspecific, with the constellation of symptoms guiding the evaluation. The patient may have been pale since birth, suggesting refractory anemia.
Birth weight may have been low, and the infant may not have gained weight well. This may be confirmed with a careful growth chart.
Chronic diarrhea and fatty stools may be noted and suggest pancreatic exocrine deficiency as a cause for failure to thrive.
Dietary history is important to exclude deficiencies of copper, riboflavin, and phenylalanine, which may cause anemia with vacuolization of hematopoietic precursors, similar to that observed in Pearson syndrome.
Previous illnesses or hospitalizations may include episodes of anorexia, vomiting, fever, and lethargy in association with electrolytic abnormalities, lactic acidosis, and hepatic dysfunction.
Development may be abnormal with the presence of neuromuscular abnormalities such as tremor, abnormal tone, and lethargy. Rarely corneal edema and hemispheric dysfunction has been reported, phenomena that are more commonly associated with KSS and MELAS. [24, 25]
History of medication exposure to rule out contact with drugs that may damage the bone marrow. For example, chloramphenicol can cause sideroblastic changes and vacuolization of hematopoietic precursors in the bone marrow, similar to the changes observed in individuals with Pearson syndrome.
Family history of unexplained pancytopenia, failure to thrive, acidosis, pancreatic insufficiency, neuromuscular dysfunction, or early death are important to document.
Some constitutional anemias and inherited bone marrow failure syndromes, such as X-linked sideroblastic anemia, Shwachman-Diamond syndrome, Fanconi anemia, and Diamond-Blackfan anemia, occur in families. A careful family history is vital to guiding investigation for these disorders.
Although mitochondriopathies can be inherited maternally, Pearson syndrome appears to be sporadic.
Physical
No pathognomonic physical characteristics are observed. Anemia causes pallor, and the patient's weight may be low for the person's age.
Hepatomegaly, often progressive, may occur. In the aforementioned AIEOP study, the investigators reported that out of 11 patients with Pearson syndrome, eight (73%) were found to have hepatomegaly, with the condition occurring in five of them before age 6 months; splenomegaly was found in just three patients (27%). [12]
Patchy erythema and photosensitivity are also reported.
Examine the patient for anomalies associated with other inherited bone marrow failure syndromes that present in the young child. For example, anomalies of the thumbs and radial ray may suggest Fanconi anemia, Diamond-Blackfan anemia, [26] or the thrombocytopenia-absent radii syndrome.
Causes
Abnormalities of mitochondrial DNA (mtDNA) (principally deletion, although rearrangements and duplications have also been reported) cause Pearson syndrome.
A study by Crippa et al suggested that in patients with Pearson syndrome, and possibly those with other mitochondrial diseases, ammonia and carbamoyl phosphate are “diverted from the urea cycle to the synthesis of nucleotides.” Biochemical analysis of four patients with Pearson syndrome found that, although low-normal ammonia levels were present, plasma levels of citrulline and arginine were low. Regression analysis indicated that each of the urea cycle’s intermediates was significantly correlated with the next, with the exception of ornithine (in its correlation with citrulline). [27]
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Characteristic vacuolization of a hematopoietic precursor in the bone marrow. (Light microscopy; 100x; Wright-Giemsa stain)
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Electron photomicrograph of a hematopoietic precursor (normoblast) with vacuolization. (Transmission electron microscopy; original 10,000x)
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Ringed sideroblast in the bone marrow (iron stain). The dark structures that form a ring around the nucleus are hemosiderin-laden mitochondria. (Light microscopy; 100x; iron stain)
