Constitutional, Metabolic, and Related Disorders

Abstract

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.