Immundeficiency 23D84.9

Immunodeficiency 23, also known as PGM3 (phosphoglucomutase 3)-associated congenital glycosylation disorder, phosphoglucomutase 3) is a rare immunodeficiency syndrome caused by a congenital disorder of glycosylation due to a mutation in the PGM3 gene .

Autosomal recessive inherited genetic defect in the PGM3 gene (chromosome 6q14) . This is characterized by a combined T-cell and B-cell immunodeficiency with pronounced atopy and autoimmunity.

Infancy, early childhood.

Clinically, immunodeficiency syndrome is characterized by recurrent bacterial and viral infections, recurrent respiratory and skin infections, atopic dermatitis, atopic diathesis, and marked elevation of serum IgE. Early neurological impairments such as developmental delay, mental retardation, ataxia, dysarthria, sensorineural hearing loss, myoclonus, and seizures are evident.

Increased T(H)2 and T(H)17 cytokine production by CD4(+) T cells, T cell lymphopenia, decreased number of memory B cellsincreased serum IgE; recurrent eosinophilia (see also hyper-IgE syndromes).

Zhang et al (2014) reported on 7 patients from a consanguineous Egyptian family. The patients had atopic dermatitis and atopic diathesis, including asthma and allergies, associated with elevated serum IgE. Skin infections were a prominent feature. Some patients had Epstein-Barr virus viremia, which was associated with lymphoma in 2 patients. Autoimmune and immune-mediated diseases were common and manifested as cutaneous leukocytoclastic vasculitis, membranoproliferative glomerulonephritis, and autoimmune neutropenia/hemolytic anemia. Five of 7 patients had rheumatoid factor. Neurologic features included developmental delay, ataxia, dysarthria, sensorineural hearing loss, and cortical myoclonus. One patient had seizures. Laboratory studies revealed neutropenia and leukopenia with particularly decreased levels of CD8 and CD27 memory B cells and increased IgE, IgG, and IgA.

In vitro studies showed that stimulation of CD4 (186940)-positive T cells from patients resulted in increased levels of certain cytokines, including IL4 (147780), IL5 (147850), IL13 (147683), and IL17 (IL17A; 603149), compared with controls. Stimulation of peripheral blood cells resulted in increased proliferation of CD4-positive and CD8-positive T cells compared with controls. There was also evidence of a glycosylation defect with decreased UDP-GalNAc and hyposialylation of O-linked serum glycans. However, glycosylation of serum transferrin (TF; 190000) was normal.

Sassi et al (2014) reported 9 patients from 4 consanguineous families with IMD23, one of which had been previously reported by Ayed et al (1987). The patients presented with recurrent respiratory infections and dermatitis, often with abscesses, during the first year of life. Fungal, viral, and bacterial infections were present. Most patients had failure to thrive and delayed psychomotor development, and some had dysmorphic facial features. Laboratory tests revealed an increase in serum IgE and eosinophils and a decreased ratio of CD4-positive to CD8-positive T cells. T-cell differentiation and proliferation were impaired in vivo.

1. Ayed K et al. (1987) Familial form of the Buckley syndrome with abnormalities of cellular immunity. Ann Pediat 34: 645-648.
2. Bjorksten B et al (1976) Recurrent bacterial infections in four siblings with neutropenia, eosinophilia, hyperimmunoglobulinemia A, and defective neutrophil chemotaxis. J Infect Dis 133: 63-71.
3. Hay BN et al (2004) Familial immunodeficiency with cutaneous vasculitis, myoclonus, and cognitive impairment. Am. J Med Genet 125A: 145-151.
4. Lundin KE et al. (2015) Susceptibility to infections, without concomitant hyper-IgE, reported in 1976, is caused by hypomorphic mutation in the phosphoglucomutase 3 (PGM3) gene. Clin Immun 161: 366-372.
5. Sassi A et al. (2014) Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J Allergy Clin Immun 133: 1410-1419.
6. Zhang Y et al. (2014) Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment. J Allergy Clin Immun 133: 1400-1409.