eMedicine Specialties > Pediatrics: General Medicine > Hematology
Pearson Syndrome: Differential Diagnoses & Workup
Updated: Jan 25, 2010
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Anemia, Fanconi
Bone Marrow Failure
Failure to Thrive
Kearns-Sayre Syndrome
MELAS Syndrome
Shwachman-Diamond Syndrome
Other Problems to Be Considered
Shwachman-Diamond syndrome is the combination of pancreatic exocrine insufficiency and neutropenia. Epiphyseal and metaphyseal dysostosis also occur in Shwachman-Diamond syndrome. Patients with Pearson syndrome may be neutropenic, but severe anemia is most characteristic.
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 can be differentiated from Pearson syndrome on the basis of a low serum copper concentration and improvement with supplemental administration of copper.
Fanconi anemia is a congenital bone marrow failure syndrome that can be distinguished from Pearson syndrome by performing physical examination, by examining the bone marrow, and by testing for chromosomal fragility. Individuals with Fanconi anemia may have short stature, hyperpigmentation, anomalies of the thumb and radius, 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. The cytopenias of Fanconi anemia often improve with androgen therapy.
Diamond-Blackfan anemia is congenital pure red cell aplasia characterized by isolated, severe, macrocytic anemia and often bony abnormalities of the thumbs and radii. 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.
Workup
Laboratory Studies
- CBC count determination with differential and reticulocyte count
- Patients with Pearson syndrome have macrocytic anemia.
- The reticulocyte count is inappropriately low.
- Some patients also have neutropenia, thrombocytopenia, or both.
- 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, though it may be intermittent.
- The ratio of lactate to pyruvate may be increased.
- Urinalysis
- Complex organic aciduria, including 3-methylglutaconic aciduria, is 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 hypothyroid, hypoparathyroid, and a deficiency in growth hormone.
- 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 are appropriate for sampling. Peripheral blood cells are also appropriate for mitochondrial DNA 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 is prudent.
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, which may occur 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)
{{mediacaption:957258_2}}- 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)
More on Pearson Syndrome |
| Overview: Pearson Syndrome |
 Differential Diagnoses & Workup: Pearson Syndrome |
| Treatment & Medication: Pearson Syndrome |
| Follow-up: Pearson Syndrome |
| Multimedia: Pearson Syndrome |
| References |
| « Previous Page | Next Page » |
References
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].
Manea EM, Leverger G, Bellmann F, et al. Pearson syndrome in the neonatal period: two case reports and review of the literature. J Pediatr Hematol Oncol. Dec 2009;31(12):947-51. [Medline].
Morel AS, Joris N, Meuli R, et al. Early neurological impairment and severe anemia in a newborn with Pearson syndrome. Eur J Pediatr. Mar 2009;168(3):311-5. [Medline].
Faraci M, Cuzzubbo D, Micalizzi C, et al. Allogeneic bone marrow transplantation for Pearson's syndrome. Bone Marrow Transplant. May 2007;39(9):563-5. [Medline].
Blaw ME, Mize CE. Juvenile Pearson syndrome. J Child Neurol. Jul 1990;5(3):187-90. [Medline].
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].
Harding AE, Hammans SR. Deletions of the mitochondrial genome. J Inherit Metab Dis. 1992;15(4):480-6. [Medline].
Kerr DS. Protean manifestations of mitochondrial diseases: a minireview. J Pediatr Hematol Oncol. Jul-Aug 1997;19(4):279-86. [Medline].
Knerr I, Metzler M, Niemeyer CM, et al. Hematologic features and clinical course of an infant with Pearson syndrome caused by a novel deletion of mitochondrial DNA. J Pediatr Hematol Oncol. Dec 2003;25(12):948-51. [Medline].
Krauch G, Wilichowski E, Schmidt KG, Mayatepek E. Pearson marrow-pancreas syndrome with worsening cardiac function caused by pleiotropic rearrangement of mitochondrial DNA. Am J Med Genet. Jun 1 2002;110(1):57-61. [Medline].
Lee HF, Lee HJ, Chi CS, Tsai CR, Chang TK, Wang CJ. The neurological evolution of Pearson syndrome: Case report and literature review. Eur J Paediatr Neurol. Apr 13 2007;[Medline].
McShane MA, Hammans SR, Sweeney M, et al. Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. Am J Hum Genet. Jan 1991;48(1):39-42. [Medline].
Muraki K, Nishimura S, Goto Y, et al. The association between haematological manifestation and mtDNA deletions in Pearson syndrome. J Inherit Metab Dis. Sep 1997;20(5):697-703. [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].
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].
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].
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].
Further Reading
Keywords
Pearson syndrome, Pearson's syndrome, Pearson marrow-pancreas syndrome, Kearns-Sayre syndrome, KSS, marrow failure, Fanconi syndrome, Fanconi's syndrome, Fanconi anemia, Fanconi's anemia, FA, Diamond-Blackfan anemia, treatment, symptoms
