Laboratory Studies
CBC count with differential and reticulocyte count
Patients with Pearson syndrome have macrocytic anemia.
The reticulocyte count is inappropriately low for the degree of anemia.
Some patients also have leukopenia, neutropenia, or thrombocytopenia.
Test of pancreatic exocrine function
Document evidence of pancreatic exocrine dysfunction.
Various direct and indirect tests are available, including the following:
- Measurement of secretory capacity induced by exogenous hormones, a test meal, or a duodenal stimulant
- Stool microscopy and analysis of fecal fat and nitrogen
- Measurement of serum pancreatic isoamylase, trypsinogen, and lipase concentrations
Measurement of serum lactic acid
Patients may have lactic acidemia, most commonly seen during intercurrent illnesses.
The ratio of lactate to pyruvate may be increased at baseline.
Urinalysis
Complex organic aciduria, including 3-methylglutaconic aciduria, has been reported.
Some patients have proximal renal tubular dysfunction that causes urinary wasting of amino acids, glucose, bicarbonate, phosphate, citrate, and urate.
Hepatic study
Hepatic transaminase values may be increased in patients with hepatic involvement.
Bilirubin levels may be increased, and albumin concentrations and coagulation values (eg, prothrombin time) may reflect a defect in synthetic function.
Endocrinologic study
Some patients have evidence of having deficiencies of thyroid, parathyroid, or growth hormones.
Analysis of mitochondrial DNA
The causative deletions of mitochondrial DNA can be demonstrated with molecular genetic analysis. Because of heteroplasmy, not all tissues contain abundant amounts of mutant mitochondrial DNA.
Bone marrow cells and peripheral blood cells are appropriate for analysis. However, because of heteroplasmy, mutant DNA may not always be found. If Pearson syndrome is suspected despite normal findings in other tissues, analysis of bone marrow should be performed.
Imaging Studies
No specific imaging studies are needed to diagnose Pearson syndrome.
MRI of the brain may be performed to further investigate a phenotypic shift to a predominantly encephalopathic or myopathic condition, such as Kearns-Sayre syndrome, which may develop in older individuals with Pearson syndrome.
Procedures
Bone marrow aspiration and biopsy are necessary to obtain bone marrow for histologic analysis.
Characteristic histologic findings of Pearson syndrome can be observed, and other causes of pancytopenia can be excluded.
Histologic Findings
The number of erythroid precursors in the bone marrow is normal or increased, and a characteristic vacuolization of hematopoietic precursors occurs (see the images below).
Characteristic vacuolization of a hematopoietic precursor in the bone marrow. (Light microscopy; 100x; Wright-Giemsa stain) 
Electron photomicrograph of a hematopoietic precursor (normoblast) with vacuolization. (Transmission electron microscopy; original 10,000x) An increased number of sideroblasts with ringed sideroblasts may be observed on iron staining (see the image below).
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) 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].
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Rotig A, Cormier V, Koll F, et al. Site-specific deletions of the mitochondrial genome in the Pearson marrow-pancreas syndrome. Genomics. Jun 1991;10(2):502-4. [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].
[Best Evidence] 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].
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