Transcobalamin II Deficiency - Transcobalamin II is the primay plasma transport protein for vitamin B12. Transcobalamin II deficiency patients develop macrocytic anemia, thrombocytopenia, and neutropenia. Immunologic abnormalities include lymphopenia, hypogammaglobulinemia, and impaired specific antibody responses. Replacement therapy with hydroxycobalamin can reverse the clinical manifestations of this disease.
Orotic aciduria - This condition is characterized by an error in pyrimidine metabolism (defective monophosphate synthase) which results in megaloblastic anemia (unresponsive to vitamin B12 or folate), growth retardation, and developmental delay. Immunologic abnormalities include T cell lymphopenia, delayed type hypersensitivity response, and hypogammaglobulinemia. Opportunistic and invasive infections have been reported in patients.
Fanconi pancytopenia - This is an AR bone marrow failure syndrome that results in anemia and thrombocytopenia. The anemia is typically macrocytic. Neutropenia secondary to marrow failure occurs in 95% of patients (T and B cell immunity is normal). Additional features include short stature, radial hypoplasia, microcephaly, renal and genital anomalies, skin hyperpigmentation, mental retardation, and characteristic facial features.