This patient is presenting with ataxia-telangiectasia characterized by cerebellar defects, telangiectasias, and IgA deficiency. It is caused by a defect in cellular DNA repair enzymes.
Ataxia-telangiectasia (AT) is a B and T cell immunodeficiency caused by defects in the ATM gene on chromosome 11 which codes for DNA repair enzymes. This makes cells hypersensitive to ionizing radiation and results in the characteristic triad of cerebellar defects, spider angiomas (telangiectasias), and IgA deficiency. Patients may also experience recurrent pulmonary infections and an increased risk of malignancy due to lack of DNA repair. On labs, an increased alpha-fetoprotein (AFP) is often seen.
Reust reviews the evaluation of primary immunodeficiency diseases in children. He states when an immunodeficiency disease is suspected, initial laboratory screening should include a complete blood count with differential and measurement of serum immunoglobulin and complement levels. The presence of lymphocytopenia on complete blood count suggests a T-cell disorder, whereas a finding of neutropenia suggests a phagocytic disorder.
Podralska et al. conducted a molecular analysis of the ATM gene in a cohort of 24 patients with ataxia-telangiectasia with the aim being to provide an updated mutational spectrum in AT patients. The status of recurrent mutation was confirmed, and ten new ATM variants were detected. Specifically, large genomic deletions were for the first time detected.
Answer 1: Defects in cellular transport do not cause AT.
Answer 2: Defects in cell surface receptors are not observed in AT. Rather, they are seen in severe combined immunodeficiency (SCID), which is characterized by defective IL-2 receptors.
Answer 3: Defects in actin cytoskeleton function are not observed in AT. Rather, they are seen in Wiskott-Aldrich syndrome in which T cells are unable to reorganize their actin cytoskeletons.
Answer 4: Defects in microtubule function are not observed in AT. Rather, they are seen in Chediak-Higashi syndrome in which there is microtubule dysfunction in phagosome-lysosome functions.
Reust CE. Evaluation of primary immunodeficiency disease in children. Am Fam Physician. 2013 Jun 1;87(11):773-8. Review
PMID:23939499 (Link to Abstract)
Podralska MJ, Stembalska A, Slezak R, Lewandowicz-Uszynska A, Pietrucha B, Koltan S, Wigowska-Sowinska J, Pilch J, Mosor M, Ziólkowska-Suchanek I, Dzikiewicz-Krawczyk A, Slomski R. Ten new ATM alterations in Polish patients with ataxia-telangiectasia. Mol Genet Genomic Med. 2014 Nov;2(6):504-11. doi: 10.1002/mgg3.98. Epub 2014 Jul 30. PubMed PMID: 25614872; PubMed Central PMCID: PMC4303220.
PMID:4303220 (Link to Abstract)