Emberger Syndrome – A Family History Over 3 Generations

# Introduction Haploinsufficiency of _GATA2_ leads to impaired genesis and function of hematopoietic stem and progenitor cells, resulting in impairment of all subsequent blood cell lineages. Germline mutations in _GATA2_ are transmitted by autosomal-dominant inheritance. Leading clinical symptoms of _GATA2_ deficiency syndromes are immunodeficiency, infections (mainly nontuberculous mycobacteria and human papillomavirus), predisposition to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), pulmonary alveolar proteinosis (PAP) and primary lymphedema. _GATA2_ mutations underlie not only Emberger syndrome (primary lymphedema and MDS), but also other syndromes like monocytopenia and mycobacterial infections syndrome (MonoMAC), dendritic cell/monocytopenia/natural killer (NK)-cell/B-cell lymphoid deficiency (DCML) and familial MDS/AML syndrome. We report the history of a Swiss family with Emberger syndrome extending over three generations. In addition, a review of the literature on _GATA2_ deficiencies is provided. # Methods Based on a general practitioner's observation of father and son sharing similar declined blood values and lymphedema, we examined the whole family for the presence of _GATA2_ mutation and a possible genotype-phenotype correlation. Publications on _GATA2_ deficiencies were researched on the PubMed database. # Results Six family members were diagnosed with _GATA2_ mutation, demonstrating individually variable penetrance and diversity of leading symptoms. # Conclusion Careful investigation of personal and family history, as well as meticulous examination, led to suspicion of the rare diagnosis of familial Emberger syndrome. Early diagnosis is mandatory for appropriate disease management

A randomized double-blind placebo-controlled trial to investigate the effects of nasal calcitonin on bone microarchitecture measured by high-resolution peripheral quantitative computerized tomography in postmenopausal women — Study protocol

<p>Abstract</p> <p>Background</p> <p>Bone microarchitecture is a significant determinant of bone strength. So far, the assessment of bone microarchitecture has required bone biopsies, limiting its utilization in clinical practice to one single skeletal site. With the advance of high-resolution imaging techniques, non-invasive in vivo measurement of bone microarchitecture has recently become possible. This provides an opportunity to efficiently assess the effects of anti-osteoporotic therapies on bone microarchitecture. We therefore designed a protocol to investigate the effects of nasal salmon calcitonin, an inhibitor of osteoclast activity, on bone microarchitecture in postmenopausal women, comparing weight bearing and non-weight bearing skeletal sites.</p> <p>Methods</p> <p>One hundred postmenopausal women will be included in a randomized, placebo-controlled, double-blind trial comparing the effect of nasal salmon calcitonin (200 UI/day) to placebo over two years. Bone microarchitecture at the distal radius and distal tibia will be determined yearly by high-resolution peripheral quantitative computerized tomography (p-QCT) with a voxel size of 82 μm and an irradiation of less than 5 μSv. Serum markers of bone resorption and bone formation will be measured every 6 months. Safety and compliance will be assessed. Primary endpoint is the change in bone microarchitecture; secondary endpoint is the change in markers of bone turnover.</p> <p>Hypothesis</p> <p>The present study should provide new information on the mode of action of nasal calcitonin. We hypothezise that - compared to placebo - calcitonin impacts on microstructural parameters, with a possible difference between weight bearing and non-weight bearing bones.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00372099</p