Somatic reversion in dedicator of cytokinesis 8 immunodeficiency modulates disease phenotype.

Background: Autosomal recessive loss-of-function mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency characterized by atopy, recurrent infections, and cancer susceptibility. A genotype-phenotype explanation for the variable disease expression is lacking.

Objective: We investigated whether reversions contributed to the variable disease expression.

The respiratory presentation of severe combined immunodeficiency in two Mennonite children at a tertiary centre highlighting the importance of recognizing this pediatric emergency.

Severe combined immunodeficiency (SCID) is considered to be a pediatric emergency, with respiratory distress being the most common presenting symptom. The authors present two cases of SCID in children <4 months of age with respiratory distress at a tertiary care centre due to a recently described homozygous CD3 delta mutation found only in the Mexican Mennonite population. Failure to respond to broad-spectrum antibiotics prompted investigation for possible SCID.

Antibiotic skin testing accompanied by provocative challenges in children is a useful clinical tool.

Background: Diagnostic testing to antibiotics other than to penicillin has not been widely available, making the diagnosis of antibiotic allergy difficult and often erroneous. There is often reluctance in performing challenges to antibiotics when standardized testing is lacking. However, while the immunogenic determinants are not known for most antibiotics, a skin reaction at a non-irritating concentration (NIC) may mean that antibodies to the native form are present in the circulation.

Defining combined immunodeficiency.

Background: Although the extreme condition of typical profound T-cell dysfunction (TD), severe combined immunodeficiency (SCID), has been carefully defined, we are currently in the process of better defining less typical T-cell deficiencies, which tend to present with autologous circulating T-cell combined immunodeficiency (CID). Because autologous cells might interfere with the outcome of bone marrow transplantation, protocols usually include conditioning regimens. Therefore it is important to define the numbers of autologous cells usually detected in patients with CID versus those with SCID.

Aplastic anemia following varicella vaccine.

Varicella zoster vaccine is a safe vaccine that is rarely associated with life-threatening complications. We describe an immunocompetent child who developed transient severe aplastic anemia concomitant with a typical clinical and laboratory-proven chickenpox syndrome 3 weeks after immunization. A causative association between the vaccine and the hematologic disease is possible, and pediatricians should be aware of this severe although rare adverse event.

Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations.

Background: Cartilage hair hypoplasia is an autosomal recessive type of metaphyseal chondrodysplasia, caused by mutations in the ribonuclease mitochondrial RNA processing (RMRP) gene. Typical features of cartilage hair hypoplasia include short stature, a predisposition to malignancy, and a variable degree of impairment of cellular immunity.

Objective: We sought to describe the heterogeneity of clinical and immunologic phenotype in 12 consecutive patients with RMRP mutations who were referred to 2 different institutions for immunologic evaluation.

Acute neurological events associated with influenza vaccination: are the WHO criteria for assessing causality adequate?

We identified neurological admissions temporally associated with influenza vaccine to determine the likelihood of causality using World Health Organization (WHO) criteria. Although all cases were categorized as possibly related to the vaccine, most had a compelling alternative explanation. This observation suggests that the current WHO criteria may not be sufficient in determining if an adverse event is truly vaccine related.