Constitutional, Metabolic, and Related Disorders

  • Kristian T. Schafernak
  • Katherine R. CalvoEmail author
Part of the Atlas of Anatomic Pathology book series (AAP)


This chapter illustrates and describes the bone marrow features of inherited bone marrow failure syndromes (e.g., Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita), as well as acquired diseases such as aplastic anemia and paroxysmal nocturnal hemoglobinuria, which can have overlapping morphologic features and are often included in the differential diagnosis of young cytopenic patients) (Figs. 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, and 4.7). Increasingly, it is recognized that adolescents and adults may harbor germline mutations in GATA2 (Fig. 4.8), RUNX1 (Fig. 4.23), and other genes, which predispose to marrow failure, myelodysplasia, and myeloid malignancy. The bone marrow features of other inherited diseases presenting with cytopenias and impaired immunity are also illustrated, including CTLA4 deficiency (Fig. 4.9), autoimmune lymphoproliferative syndrome (ALPS) (Fig. 4.10), activated PI3K-delta syndrome (Figs. 4.11, 4.12, 4.13, 4.14, 4.15, 4.16 and 4.17), Chédiak-Higashi syndrome (Figs. 4.18, 4.19 and 4.20), WHIM syndrome (Fig. 4.21), and chronic granulomatous disease (Fig. 4.22). Inherited diseases resulting primarily in single-lineage cytopenias involving erythroid (e.g., severe congenital neutropenia (Fig. 4.5)), myeloid (e.g., severe congenital neutropenia (Fig. 4.5)), and platelets (e.g., familial thrombocytopenia (Fig. 4.23)) are also presented. Marrow diseases associated with toxic and/or metabolic states and storage diseases (e.g., Gaucher disease (Fig. 4.24), Niemann-Pick disease (Figs. 4.25, 4.26, and 4.27), hemophagocytic lymphohistiocytosis (Fig. 4.28), megaloblastic anemia (Figs. 4.29, 4.30 and 4.31), arsenic toxicity (Fig. 4.32), renal osteodystrophy (Fig. 4.33), and osteopetrosis (Fig. 4.34) are included in this chapter.


Bone marrow failure Inherited syndromes Acquired syndromes Aplastic anemia GATA2 deficiency Congenital disorders with abnormal bone marrow Metabolic bone marrow disorders Toxicity 



Work in this chapter was in part supported by the Intramural Research Program of the National Institutes of Health and the NIH Clinical Center.

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Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicinePhoenix Children’s HospitalPhoenixUSA
  2. 2.Department of Laboratory MedicineNational Institutes of Health Clinical Center10 Center Dr. Bldg 10/2C306 BethesdaUSA

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