Immundeficiency 21 D84.-

Immunodeficiency-21 (IMD21) is a rare immune disorder caused by a heterozygous mutation in the GATA2 gene (137295) on chromosome 3q21. This primary immunodeficiency, referred to as IMD21, DCML or MONOMAC, is characterized by severely reduced or absent numbers of monocytes (constant feature - Vinh et al 2010), B lymphocytes, natural killer (NK) lymphocytes and circulating and tissue dendritic cells (DCs), with minor or no T cell numbers affected (Bigley V et al 2011).

5 months to 60 years; average age: 32 years

In larger collectives with this primary immune disorder, susceptibilities to disseminated nontuberculous mycobacterial infections, to viral infections, especially with human papillomaviruses, and fungal infections (16%) as well as to histoplasmosis have been demonstrated (Spinner M A et al. 2014). Furthermore, pulmonary alveolar proteinosis (18%), lymphedema (11%), and hypothyroidism (14%) may develop.

Hemograms and lymphocyte phenotyping: B lymphocytopenia (86 %), NK lymphocytopenia (82 %), monocytopenia (78 %), CD4 lymphocytopenia (51 %) and neutropenia (47 %). 84 % of patients who underwent bone marrow biopsy had myelodysplastic syndrome. Furthermore, karyotypic abnormalities including monosomy 7 and trisomy 8 can be detected.

A bone marrow transplant is the only cure.

Most patients develop one or more malignancies, including myelodysplastic syndromes or myeloid leukemia

Primary lymphedema with myelodysplasia (OMIM: 614038) or Emberger syndrome is an allelic disorder with overlapping clinical features.

1. Bigley V et al (2011) The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. J Exp Med 208: 227-234.
2. Biron C A et al (1989) Severe herpesvirus infections in an adolescent without natural killer cells. New Eng J Med 320: 1731-1735.
3. Cuellar-Rodriguez J et al (2011) Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency. Blood 118: 3715-3720.
4. Dickinson RE et al (2011) Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood 118: 2656-2658.
5. Johnson K D et al (2112) Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity. J Clin Invest 122: 3692-3704.

6. Spinner M A et al (2014) GATA2 deficiency: a protean disorder of hematopoiesis, ymphatics, and immunity. Blood 123: 809-821.

7. Vinh DC et al (2010) Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 115: 1519-1529.