August 2020 — Molecular

A 4 month-old Caucasian boy with an unremarkable family history was hospitalized for new-onset pancytopenia and was diagnosed with anaplastic anemia of unknown etiology. Additionally, the patient had developmental delays with hypotonia, pancreatic insufficiency and failure to thrive. At age 25 months he was hospitalized for “septic” appearance. Lab values were remarkable for elevated liver function enzymes, blood ammonia levels, and lactic acidemia. A rare inherited condition was suspected and a muscle biopsy was sent for molecular testing (Fig.1).

Which of the following syndromes/diseases best fits the clinical presentation and molecular testing of this patient?

  • Diamond-Blackfan anemia
  • Evans syndrome
  • Pearson syndrome
  • Fanconi anemia

The correct answer is...

The correct answer is Pearson syndrome.

Pearson syndrome is a rare inherited disorder, which is caused by deletion in mitochondrial DNA. Heteroplasmy and extent to which different tissues are affected lead to variable clinical presentation and disease onset. Most common symptoms include transfusion dependent refractory anemia, bone marrow biopsy showing cytoplasmic vacuoles in erythroid precursors, lactic acidosis and pancreatic insufficiency. Molecular studies showing large deletion in mitochondrial DNA are important for diagnosis.

Diamond–Blackfan anemia is a rare syndrome, which is not related to mitochondrial DNA but it is a disease of ribosomal biogenesis and function. Clinical presentation includes short stature, red cell aplasia and increased risk of malignancy.

Fanconi anemia is a rare autosomal recessive bone marrow failure syndrome, which is due to mutations in proteins involved in DNA repair. Major complications are aplastic anemia and high probability for developing of malignancies. Deletion in mitochondrial DNA does not play a role in the pathogenesis.

Evans syndrome is an autoimmune condition that presents with cytopenias, commonly includes autoimmune hemolytic anemia and immune thrombocytopenia. Deletion in mitochondrial DNA does not play a role in the pathogenesis.

1. Jyothi Muni Reddy, Joe Jose, Anand Prakash, Shanthala Devi, Pearson Syndrome: A Rare Inborn Error of Metabolism With Bone Marrow Morphology Providing a Clue to Diagnosis, Sudan J Paediatr. 2019;19(2):161-164
2. Wild KT, Goldstein AC, Muraresku C, Ganetzky RD, Broadening the phenotypic spectrum of Pearson syndrome: Five new cases and a review of the literature. Am J Med Genet A. 2020 Feb;182(2):365-373
3. Sarah Ball, Diamond Blackfan Anemia, Hematology Am Soc Hematol Educ Program 2011;2011:487-91
4. Alter BP, Fanconi anemia and the development of leukemia. Best Pract Res Clin Haematol. 2014 Sep-Dec;27(3-4):214-21
5. Rivalta B et al, Evans Syndrome in Childhood: Long Term Follow-Up and the Evolution in Primary Immunodeficiency or Rheumatological Disease. Front Pediatr. 2019 Jul 23;7:304

Photo of Krasimira (Krasi) Rozenova, M.D., Ph.D Krasimira (Krasi) Rozenova, M.D., Ph.D.
Resident, Anatomic and Clinical Pathology (2019-2020)
Mayo Clinic
Photo of Linda Hasadsri, M.D., Ph.D. Linda Hasadsri, M.D., Ph.D.
Consultant, Laboratory Genetics and Genomics
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

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