Long-term follow-up of patients with Herlitz-type junctional epidermolysis bullosa.

BACKGROUND: Junctional epidermolysis bullosa, type Herlitz (JEB-H) is a rare, autosomal recessive disease caused by absence of the epidermal basement membrane adhesion protein laminin-332. It is characterized by extensive and devastating blistering of the skin and mucous membranes, leading to death in early childhood. OBJECTIVES: To present the results of the long-term follow-up of a cohort of patients with JEB-H, and to provide guidelines for prognosis, treatment and care. METHODS: All patients with JEB-H included in the Dutch Epidermolysis Bullosa (EB) Registry between 1988 and 2011 were followed longitudinally by our EB team. Diagnosis was established using immunofluorescence antigen mapping, electron microscopy and DNA analysis. RESULTS: In total, we included 22 patients with JEB-H over a 23-year period. Their average age at death was 5.8 months (range 0.5-32.6 months). The causes of death were, in order of frequency: failure to thrive, respiratory failure, pneumonia, dehydration, anaemia, sepsis and euthanasia. The pattern of initial weight gain was a predictor of lifespan in these patients. Invasive treatments to extend life did not promote survival in our patients. CONCLUSIONS: It is important to diagnose JEB-H as soon as possible after birth so that the management can be shifted from life-saving to comfort care. The palliative end-of-life care can take place in hospital, but is also safe in the home setting. Suffering in patients with JEB-H can become so unbearable that in some patients who do not respond to adequate analgesic and sedative treatment, newborn euthanasia, performed according to the Groningen protocol, is legally permitted in the Netherlands.

Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults.

BACKGROUND: In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for DBPCFCs to facilitate oral challenge tests in all age groups, including young children, while maximizing the top dose in an acceptable volume. METHODS: Recipes were developed and subsequently validated by a panel recruited by a matching sensory test. The best 30% of candidates were selected to participate in sensory testing using the paired comparison test. RESULTS: For young children, three recipes with cow's milk and one recipe with peanut could be validated which may be utilized in DBPCFCs. For children older than 4 years and adults, one recipe with egg, two with peanut, one with hazelnut, and one with cashew nut were validated for use in DBPCFCs. CONCLUSIONS: All recipes contained larger amounts of allergenic foods than previously validated. These recipes increase the range of validated recipes for use in DBPCFCs in adults and children.

Forty-eight new cases with infertility due to balanced chromosomal rearrangements: detailed molecular cytogenetic analysis of the 90 involved breakpoints.

A molecular cytogenetic study was performed on 48 infertile patients who were identified as carriers of balanced translocations (40 cases), inversions (6 cases) or insertions (2 cases) by means of banding cytogenetics. Cases with a Robertsonian translocation or pericentric inversion 2 or 9 were not included. In summary, 100 break-events occurred in these patients, and 90 different chromosomal regions were involved. Thus, this study confirmed the presence of abnormal karyotypes in a subgroup of patients seeking infertility treatment. Breaks were demonstrated to appear preferentially in GTG-light bands in these patients. Furthermore, the observed breakpoints were associated with genomic regions prone to instability due to the presence of segmental duplications. Nonetheless, further detailed molecular analysis will be necessary in the future to characterize the mechanisms and genetic basis for this phenomenon.