A Novel CD3G Mutation in a Taiwanese Patient With Normal T Regulatory Function Presenting With the CVID Phenotype Free of Autoimmunity-Analysis of all Genotypes and Phenotypes.

The T-cell receptor (TCR)/CD3 complex is crucial for T-cell development and regulation. In humans, CD3D, CD3E, and CD3Z gene defects cause severe combined T- and B-cell immunodeficiency. However, CD3G mutations alone lead to a less severe condition, which is mainly characterized by autoimmunity. In the present study, we report the case of a 36-year-old male who presented with recurrent sinopulmonary infections without opportunistic infections; this was compatible with hypogammaglobulinemia, but normal PHA-lymphocyte proliferation. This patient had the common variable immunodeficiency (CVID) phenotype and received regular immunoglobulin infusions over 20-years; he gradually developed nodular regenerative hyperplasia over a 5-year period. Distinct from the previously reported CD3G mutations, which mainly present as autoimmunity, the novel CD3G deletion (c.del213A) in our patient caused an obvious decrease in switched memory B cells and diminished CD40L expression. However, sufficient Treg suppression function was maintained so that he remained free of autoimmune thyroiditis (AIT), inflammatory bowel disease (IBD), and autoimmune pancytopenia. A PubMed search for this rare disease entity revealed seven Turkish and two Spanish patients (five unrelated families). Among a total of 20 alleles, there were 14 splicing mutations (80(-1)G>C), two missense mutations (c.1G>A), two nonsense mutations (c.250A>T), and two deletions (c.del213A). Three patients presented with isolated AIT without significant infections. Three patients died, one from a severe infection at 31 months, one from post-transplant respiratory failure due to viral pneumonia at 17 months, and one from graft-vs.-host disease at 47 months. Those experiencing opportunistic infections, severe life-threatening infections in need of hematopoietic stem cell transplantation, and IBD-like diarrhea had a significantly higher mortality rate compared with those without these features (p = 0.0124, p = 0.01, and p = 0.0124, respectively). The patients with AIT had a significantly better prognosis (p = 0.0124) to those without AIT. Our patient with the novel CD3G mutation presented with predominant B-cell deficiency overlapping with the CVID phenotype but without recognizable autoimmunity, which was consistent with his normal Treg suppression function.

Acute hypercapnic respiratory failure due to thyrotoxic periodic paralysis.

Acute hypercapnic respiratory failure is a potentially life-threatening complication of profound hypokalemia usually seen in patients with large total-body potassium (K+) deficits. It has rarely been reported in thyrotoxic periodic paralysis (TPP), which is due to intra-cellular shifts of K+. The authors report on a 29-year-old man who presented with sudden onset of muscle paralysis in all extremities and acute progressive respiratory insufficiency requiring artificial respiratory support. He was treated with intravenous KCl. After six hours, muscular strength had returned to normal, with plasma K+ concentration of 3.0 mmol/L. At the eighth hour, rebound hyperkalemia (6.6 mmol/L) developed with high-tented T waves, even after the KCl was discontinued. Ventilatory support was uneventfully weaned at 14 hours. Elevated free thyroxine and undetectable thyroid-stimulating hormone confirmed the diagnosis of TPP. TPP should be kept in mind as a cause of acute respiratory failure in association with acute muscle weakness to avoid delayed diagnosis and improper management.

Life-threatening hypokalemia in an asthmatic patient treated with high-dose hydrocortisone.

Although modest hypokalemia is frequently observed in asthmatic patients being treated with bronchodilators, profound hypokalemia and metabolic alkalosis are rarely reported in patients receiving high-dose hydrocortisone (HC). We describe a 66-year-old man who complained of generalized muscle weakness, shallow respiration, and palpitations after receiving high-dose intravenous HC (total dose, 2400 mg over 4 days) to treat a severe asthma attack. During this therapy, there was a weight gain of 1.0 kg. An electrocardiogram revealed ventricular arrhythmia with frequent premature ventricular contractions. Hypokalemia was profound, with plasma potassium (K+) concentration of 1.7 mEq/L, and associated with renal potassium wasting, as evidenced by a transtubular potassium concentration gradient of 12; metabolic alkalosis (plasma HCO3-, 37 mEq/L) was also present. When treated with spironolactone, KCl supplementation, and substitution of HC with prednisolone, his plasma K+ concentration rapidly normalized, metabolic alkalosis was corrected, and arrhythmia disappeared within 3 days. Because of unwanted mineralocorticoid side-effects, high-dose HC may cause life-threatening hypokalemia in asthmatic patients. Because of these potential risks, plasma acid-base and electrolyte concentrations should be monitored frequently in any patient treated with high-dose HC.

Correlation of neutrophil phagocytosis and lymphocyte adhesion molecules in exertional heat stroke.

BACKGROUND: Increased susceptibility to infections has been shown in patients with classic heat stroke. Although immunologic and inflammatory responses may be important factors, the direct role of circulating neutrophil phagocytosis and lymphocyte adhesion molecule expression has yet to be investigated in exertional heat stroke (ExHS). DESIGN: Circulating neutrophil phagocytosis and lymphocyte adhesion molecule CD11a and CD11b expression were examined in 17 patients with ExHS and 17 exertional control subjects (ExC). RESULTS: Patients with ExHS showed significantly increased total leukocyte, neutrophil, and lymphocyte counts, attenuated neutrophil phagocytosis ability, and higher expression of CD11a and CD11b in the acute phase of ExHS, compared with the recovery phase of ExHS and ExC. Although there were no correlations between body temperature and phagocyte function or adhesion molecules, a negative correlation between phagocytosis and CD11a/CD11b was present. CONCLUSION: Increased leukocyte count with decreased circulating neutrophil phagocytic capacity and increased expression of lymphocyte adhesion molecules may in part explain the susceptibility to infections in ExHS.

Thyrotropin-secreting pituitary adenoma presenting as hypokalemic periodic paralysis.

Thyrotropin (TSH)-secreting pituitary adenoma presenting with hypokalemic periodic paralysis is extraordinarily rare and may be misdiagnosed. We describe a 44-year-old man who suffered from acute muscle weakness and inability to ambulate upon awakening in the morning. Physical examination showed hypertension, tachycardia, and symmetrical flaccid paralysis of all extremities. The major biochemical abnormality was hypokalemia (K+, 2.0 mmol/L) with low urine K+ excretion. A thyroid function study revealed elevated thyroid hormone levels and inappropriately high TSH concentrations (2.10 microU/mL). Brain magnetic resonance imaging delineated a pituitary tumor with suprasellar extension. After trans-sphenoidal removal of tumor, he became clinically and biochemically euthyroid without any further attack of paralysis. Pathological findings confirmed a TSH-secreting adenoma with exclusive TSH immunostaining. TSH-secreting pituitary adenoma must be kept in the differential diagnosis in any thyrotoxic periodic paralysis patients with detectable TSH levels to avoid delaying diagnosis and management.