Long-term follow-up of children with risk organ-negative Langerhans cell histiocytosis after 2-chlorodeoxyadenosine treatment

The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO−) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO− LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3–19·7 years) and the median follow-up after was 5·4 years (range, 0·6–15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO− LCH. Appropriate management of induced immune deficiency is mandatory.     

Overbite depth indicator and anteroposterior dysplasia indicator cephalometric norms for African Americans

Objectives:To examine normal Overbite Depth Indicator (ODI) and Anteroposterior Dysplasia Indicator (APDI) values in African Americans and to compare them with mean values from white patients. Secondary aims were to compare mean ODI and APDI values among different age, gender, and combined age-gender groups in African American patients.Materials and Methods:Lateral cephalometric radiographs of 160 African American patients (97 boys and 63 girls; age, 7 to 14 years) with normal occlusion and no history of orthodontic treatment were collected from the Bolton-Brush Growth Center. Cephalometric images were hand traced, and ODI and APDI values were assessed. Two-sample t tests were used to compare mean ODI and APDI values between African American and white patients; and between male and female African American patients. One-way analysis of variance, followed by the Tukey test, was used to compare mean ODI and APDI values among different African American age and combined age-gender groups.Results:Mean ODI and APDI values were significantly lower (P < .0001) in African American than white patients with normal occlusion and no history of orthodontic treatment. Mean ODI and APDI values increased with age in African American patients, and there were no significant gender differences.Conclusions:The mean ODI and APDI values in 7- to 14-year-old African Americans with normal occlusion and no history of orthodontic treatment were 70.9° and 78.1°, respectively, and were significantly lower than the mean values for white patients in the same age range.     

Pertussis Diagnosis in the 21st Century: Progress and Pitfalls, Part I

Bordetella pertussis is the causative agent of pertussis, also called whooping cough or the cough of 100 days. Infection can result in significant morbidity and mortality, particularly in young infants. Prior to the availability of effective vaccines, pertussis was a major cause of childhood disease. With the advent of such vaccines, the incidence of disease declined dramatically into the 1970s. However, pertussis is still present, with peaks occurring every 3 to 5 years, and the number of cases has been increasing in the United States since the 1980s. With recent reports of numerous outbreaks of pertussis, there is heightened interest in the control and diagnosis of the disease. Efforts to increase immunity through vaccination and also to improve the clinical and laboratory diagnosis of the disease are very important. Part I of this two-part article will review a recent outbreak of pertussis that occurred in California and discuss the biology of the genus Bordetella, followed by the clinical presentation of disease and recommendations for recent vaccination protocols and guidelines for diagnosis. Part II of this article will be published in the August 15 issue of this newsletter and will review laboratory methods available for diagnosis, along with their problems and pitfalls.     

C7orf10 encodes succinate-hydroxymethylglutarate CoA-transferase, the enzyme that converts glutarate to glutaryl-CoA

Glutarate, a side-product in the metabolism of tryptophan and lysine, is metabolized by conversion to glutaryl-CoA by a transferase using succinyl-CoA as a coenzyme donor. The enzyme catalyzing this conversion has not been formally identified. However, a benign form of glutaric aciduria (glutaric aciduria type III) is due to mutations in C7orf10, a putative member of the coenzyme A transferase class III family. In the present work, we show that recombinant human C7orf10 catalyzes the succinyl-CoA-dependent conversion of glutarate to glutaryl-CoA. C7orf10 could use many dicarboxylic acids as CoA acceptors, the best ones being glutarate, succinate, adipate, and 3-hydroxymethylglutarate. Confocal microscopy analysis of CHO cells transfected with a C7orf10-GFP fusion protein indicated that C7orf10 is a mitochondrial protein, in agreement with the presence of a predicted mitochondrial propeptide at its N-terminus. The effect of a missense mutation (p.Arg336Trp) found in the homozygous state in several patients with glutaric aciduria type III and present in the general population at a low frequency was also investigated. The p.Arg336Trp mutation led to the production of insoluble and inactive C7orf10 both in Escherichia coli and in HEK293T cells. These findings indicate that C7orf10 is implicated in the metabolism of glutarate, but possibly also of longer dicarboxylic acids. Homologues of this enzyme are found in numerous bacterial operons comprising also a putative glutaryl-CoA dehydrogenase, indicating that an enzyme with similar specificity exists in prokaryotes.