A 6-year-old boy presents with his mother to the pediatrician for evaluation of progressive unsteadiness, which his mother first noticed when the patient was a toddler. She reports that his trunk has always been unstable and that he seems to wobble when he walks. Past medical history is significant for recurrent sinopulmonary infections. He does not take any medications. Vital signs are within normal limits. Physical examination is significant for an ataxic gait and telangiectasias on the bilateral conjunctiva. Results of a complete blood count indicate mild lymphopenia and no other abnormalities.
A mutation in which of the following genes is most likely responsible for this patient’s presentation?
A) ATM gene mutation
Ataxia telangiectasia is an autosomal recessive condition commonly caused by mutations in the ATM gene, which impairs double stranded DNA repair and renders the individual extremely sensitive to radiation. Accumulation of mutations typically presents with ataxia, telangiectasias, low IgA/IgG/IgE, lymphopenia, and elevated alpha-fetoprotein (AFP).
Answer choice B: BTK gene mutation, is incorrect. BTK mutation is the etiology of X-linked agammaglobulinemia in which B cells fail to mature, leading to low levels of all immunoglobulins. Patients with this disease typically present after 6 months of age with bacterial and enteroviral infections due to the loss of maternal IgG at this point.
Answer choice C: LYST gene mutation, is incorrect. LYST mutation is a cause of Chédiak-Higashi syndrome, which disrupts lysosomal trafficking. Patients with this disease present with partial albinism, peripheral neuropathy, neurodegeneration, and pancytopenia.
Answer choice D: STAT3 gene mutation, is incorrect. Mutation in STAT3 leads to hyper-IgE syndrome, an autosomal dominant condition in which Th17 cells are deficient and neutrophils cannot be recruited to infection sites. This leads to non-inflamed staphylococcal abscesses and typically presents with high levels of IgE. Coarse facies, retained primary teeth, and atopic dermatitis may also be present.
Answer choice E: WAS gene mutation, is incorrect. A mutation in WAS is responsible for Wiskott-Aldrich syndrome, an X-linked recessive disease in which disorganization of the actin cytoskeleton leads to defective antigen presentation by leukocytes. Thrombocytopenia and elevated IgA levels are typically present.
Key Learning Point
Ataxia-telangiectasia is caused by defects in the ATM gene. It typically presents in the first decade of life with ataxia, telangiectasia, and frequent sinopulmonary infections.
