Diagnostic Considerations
Pearson syndrome is currently diagnosed via a positive genetic test for mtDNA deletions. [28] Clinical features may help to suggest the presence of Pearson syndrome over other constitutional bone marrow failure syndromes, but in general, molecular diagnosis is available and preferred.
Shwachman-Diamond syndrome is the combination of pancreatic exocrine insufficiency and neutropenia. Epiphyseal and metaphyseal dysostosis also occur in Shwachman-Diamond syndrome. Patients with both syndromes may have cytopenias of all 3 lineages, but patients with Pearson syndrome have severe macrocytic anemia as the most characteristic finding, and those with Shwachman-Diamond syndrome have neutropenia.
Fanconi anemia is a congenital bone marrow failure syndrome that can be distinguished from Pearson syndrome by the frequent presence of physical abnormalities, absence of pancreatic malabsorption, and by increased chromosomal fragility. Individuals with Fanconi anemia often, but not always, have short stature, hyperpigmentation, anomalies of the thumb and radial ray, and other congenital abnormalities. No vacuolization of hematopoietic precursors occurs in Fanconi anemia, and chromosomes from patients with Fanconi anemia develop breaks when incubated with diepoxybutane, Mitomycin C, or other clastogenic agents. The cytopenias of Fanconi anemia usually start with thrombocytopenia and mild macrocytic anemia.
Diamond-Blackfan anemia is congenital pure red cell aplasia characterized by isolated, severe, macrocytic anemia and, often, bony abnormalities of the thumbs and radial rays. Serum adenosine deaminase levels are usually increased in Diamond-Blackfan anemia, and no pancreatic insufficiency is observed. Many cases of Diamond-Blackfan anemia respond to glucocorticoid therapy.
Myelodysplastic syndrome (MDS), specifically the World Health Organization (WHO) classification refractory cytopenia of childhood, may also display cytoplasmic vacuolation. Patients with MDS may have additional cytogenetic abnormalities in the bone marrow and, of course, a negative genetic test for mtDNA deletion. [28]
Deletion of 22q11.2, usually associated with DiGeorge and velocardiofacial syndrome, may also display myelodysplastic features and cytoplasmic vacuolation. [29]
Hereditary sideroblastic anemia lacks the characteristic vacuolization of marrow precursors, and no concomitant pancreatic insufficiency occurs. Sideroblastic anemia may respond to pyridoxine or pyridoxal phosphate.
Copper deficiency, either primary or secondary on the basis of excess zinc intake, is associated with neuropathy, cytopenias, myelodysplastic features and cytoplasmic vacuolation. [30] Hypocupremia can be differentiated from Pearson syndrome on the basis of a low serum copper concentration and improvement with supplemental administration of copper.
Differential Diagnoses
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Diamond Blackfan anemia
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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)
