An Unusual Presentation of X-Linked Agammaglobulinemia

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http://www.apnet.com/www/journal/aaaai/5222.html#5222

AAAAI 56th Annual Meeting

Abstract No.: 657

An Unusual Presentation of X-Linked Agammaglobulinemia

Jaffe, Rhoda Kagan

Subject: 23 Immunodeficiency

Keywords:

X-linked agammaglobulinemia (XLA) is a disorder of B cell maturation which

generally manifests in early childhood, before the age of two years, with

recurrent severe bacterial infections. Mutations in the tyrosine kinase

gene, BTK, block maturation of B cells and hence lead to low or absent

levels of immunoglobulin and lack of antibody response to vaccine. There

have been very few reports of milder XLA phenotypes presenting in older

individuals, and they are not usually associated with a complete lack of

mature B cells. We describe a family of three boys with a distinctly late

presentation and complete lack of mature B cells.

The index case was the middle son, who was diagnosed with XLA after

presenting with pneumococcal bacteremia with a paravertebral infectious

process at age 16. His past medical history was significant for

hospitalization at age 3 for 4 weeks of watery diarrhea and rectal prolapse,

with no defined etiology by the end of the hospitalization. He had two

episodes of pneumonia at ages 1 and 10. He had otherwise been healthy. He

had varicella, and received all immunizations to date, including oral polio,

without adverse effect. Immunological workup at the time of his

hospitalization for pneumoccocal bacteremia was remarkable for low IgG

(5.18), IgM (0.26), and IgA (0.06), lack of mature B cells , and poor

response to vaccines. Complement levels, and T cell numbers and

proliferative responses were normal. Family history was notable for

recurrent pneumonia, streptococcal cellulitis, and UTI with renal abscess in

his older brother, who had been worked up for immunodeficiency in early

childhood, but was found to have normal immunoglobulin levels. Later tests

performed after his brother's diagnosis revealed that he too had no mature B

cells. The youngest brother, age 14 at diagnosis, had recurrent otitis media

in early childhood but had otherwise been healthy. He too had absent mature

B cells, and poor response to vaccine.

Genomic DNA analysis revealed a deletion of three consecutive thymidines

near the splice junction of intron 16. cDNA analysis revealed multiple bands

including a deletion of exon 16, which has previously been implicated in a

mild phenotype of XLA. The intron deletion presumably affects splicing,

leading to unstable products and an absence of BTK.

This case report reemphasizes the variability of XLA, and the importance

of examining specific B cell subsets in addition to quantitative

immunoglobulins in milder phenotypes, and is also a second report of a mild

XLA phenotype associated with absence of exon 16.