Agammaglobulinemia 9 (autosomal recessive), mutation due to SLC39A7 D81.4

Autosomal recessive agammaglobulinemia-9 (AGM9) is a primary immunodeficiency syndrome caused by a homozygous or compound heterozygous mutation in the SLC39A7 gene (601416) on chromosome 6p21. Clinically, recurrent bacterial infections are prominent. Other features are failure to thrive and skin involvement (blistering, eczematous skin lesions).

Absence of B cells.

The severity of the disorder varies: more severe cases may require hematopoietic stem cell transplantation, while others can be effectively treated with Ig replacement therapy (Anzilotti et al. 2019).

Anzilotti et al (2019) reported on 6 patients from 5 unrelated families with a primary immunodeficiency associated with agammaglobulinemia and absent circulating B cells. The patients, ranging in age from 3.5 to 32 years, were of white European, South Asian, and Hispanic ancestry. Clinical details were limited, but all had recurrent bacterial infections. All had various skin lesions, including vesicular dermatosis, mild eczematous rash, seborrheic dermatitis, and transient necrotizing granulomatous rash. One individual (P4) had iron deficiency anemia, vitamin D deficiency, enteropathy, and failure to thrive. Two siblings (P1 and P2) with the most severe phenotype with blistering dermatosis (subepithelial blistering) had failure to thrive and developed thrombocytopenia; P2 had high-grade sensorineural deafness. Examination of the bone marrow of P1 and P2 showed progressive disruption of B-cell development, with an excess of pro-B cells compared with pre-B cells and an even smaller proportion of immature B cells compared with pre-B cells. T-cell number and function were normal in all patients. P1 and P2 underwent hematopoietic stem cell transplantation, and symptoms resolved. The other patients responded well to Ig replacement therapy.

In 6 patients from 5 unrelated families with AGM9, Anzilotti et al (2019) identified compound heterozygous or homozygous mutations in the SLC39A7 gene (see, e.g., 601416.0001-601416.0005). The mutations found by exome sequencing and confirmed by Sanger sequencing. Anzilotti C et al.(2019) concluded that proper zinc dynamics are essential for proper B cell development.

1. Anzilotti C et al.(2019) An essential role for the Zn(2+) transporter ZIP7 in B cell development. Nature Immun. 20: 350-361.
2. Woodruff G et al. (2018) The Zinc Transporter SLC39A7 (ZIP7) Is Essential for Regulation of Cytosolic Zinc Levels. Mol Pharmacol 94:1092-1100.