A 5-month-old boy is brought to the clinic due to fussiness and fever for 2 days. His medical history is significant for previous episodes of otitis media, oral candidiasis, and gastroenteritis due to rotavirus. The patient is at the third percentile for weight. His temperature is 39.3 C (102.8 F), pulse is 120/min, respiratory rate is 28/min, and blood pressure is 80/60 mm Hg. Physical examination shows an erythematous, bulging right tympanic membrane with poor mobility on pneumatic otoscopy. The lymph nodes are not palpable, and the tonsils are not visualized. Laboratory results are as follows: Which of the following is the most likely etiology of this patient's condition?

Question

A 5-month-old boy is brought to the clinic due to fussiness and fever for 2 days.  His medical history is significant for previous episodes of otitis media, oral candidiasis, and gastroenteritis due to rotavirus.  The patient is at the third percentile for weight.  His temperature is 39.3 C (102.8 F), pulse is 120/min, respiratory rate is 28/min, and blood pressure is 80/60 mm Hg.  Physical examination shows an erythematous, bulging right tympanic membrane with poor mobility on pneumatic otoscopy.  The lymph nodes are not palpable, and the tonsils are not visualized.  Laboratory results are as follows:  Which of the following is the most likely etiology of this patient's condition?

Quizplus · Accepted Answer

11ec25c8_d62a_83ee_bc81_fb123279055d_MD0003_00 This patient has recurrent infections, failure to thrive, hypogammaglobulinemia, and markedly low T cell counts. These findings are consistent with severe combined immunodeficiency (SCID), a disorder of defective T cell development leading to severe B cell dysfunction. The absence of T cells causes severe defects in cellular immunity, increasing the risk for infection due to viruses, fungi, and opportunistic pathogens (eg, Pneumocystis jirovecii). The loss of CD4+ T cells also leads to B cell (humoral immunity) dysfunction, increasing the risk for sinopulmonary and gastrointestinal bacterial infections. In addition to infection, chronic diarrhea and failure to thrive in infancy as well as absence of lymphoid tissue on examination are typical. Laboratory findings of SCID include lymphopenia and hypogammaglobulinemia. Stem cell transplant is the only treatment and should be performed as early as possible. Therefore, SCID is included in routine newborn screening in the United States and is detected by the absence of T cell receptor excision circles (circular DNA excreted by developing T cells in the thymus) in dried blood. (Choice A) Bruton (or X-linked) agammaglobulinemia is characterized by absent B cells, low serum immunoglobulins, and normal T cell concentrations. Patients present with recurrent sinopulmonary and gastrointestinal infections; examination shows an absence of lymphoid tissue. (Choice B) Chronic granulomatous disease is a defect of the NADPH oxidase in phagocytic cells, which leads to impaired killing of catalase-positive organisms (eg, Staphylococcus aureus, Serratia marcescens). Affected patients have recurrent skin and soft tissue infections but normal lymphocyte and immunoglobulin concentrations. (Choice C) Common variable immunodeficiency (CVID) causes recurrent sinopulmonary or gastrointestinal bacterial infections due to hypogammaglobulinemia. In contrast to Bruton agammaglobulinemia, CVID is less severe and presents at a later age with normal T cell and B cell counts. (Choice E) Wiskott-Aldrich syndrome, an X-linked recessive disease, presents in early infancy with eczema and bleeding (eg, post circumcision, bleeding from umbilical stump) due to thrombocytopenia, which is not present in this patient. T cell dysfunction and hypogammaglobulinemia worsen with age and present as bacterial, viral, and opportunistic infections. Educational objective: Severe combined immunodeficiency is a life-threatening condition caused by defective T cell maturation. Affected patients present with failure to thrive, recurrent infections (viral, fungal, bacterial), and extremely low lymphocyte concentrations. Treatment requires stem cell transplantation. References: Primary immunodeficiency in the neonate: Early diagnosis and management. (http://www.ncbi.nlm.nih.gov/pubmed/26776073) Severe combined immunodeficiency disorders. (http://www.ncbi.nlm.nih.gov/pubmed/26454313)

A 5-Month-Old Boy Is Brought to the Clinic Due to Fussiness