Molecular and clinical analysis of ALPL in a cohort of patients with suspicion of Hypophosphatasia.

Hypophosphatasia (HPP) is a rare autosomal dominant or recessive metabolic disorder caused by mutations in the tissue nonspecific alkaline phosphatase gene (ALPL). To date, over 300 different mutations in ALPL have been identified. Disease severity is widely variable with severe forms usually manifesting during perinatal and/or infantile periods while mild forms are sometimes only diagnosed in adulthood or remain undiagnosed. Common clinical features of HPP are defects in bone and tooth mineralization along with the biochemical hallmark of decreased serum alkaline phosphatase activity. The incidence of severe HPP is approximately 1 in 300,000 in Europe and 1 in 100,000 in Canada. We present the clinical and molecular findings of 83 probands and 28 family members, referred for genetic analysis due to a clinical and biochemical suspicion of HPP. Patient referrals included those with isolated low alkaline phosphatase levels and without any additional clinical features, to those with a severe skeletal dysplasia. Thirty-six (43.3%) probands were found to have pathogenic ALPL mutations. Eleven previously unreported mutations were identified, thus adding to the ever increasing list of ALPL mutations. Seven of these eleven were inherited in an autosomal dominant manner while the remaining four were observed in the homozygous state. Thus, this study includes a large number of well-characterized patients with hypophosphatasemia which has permitted us to study the genotype:phenotype correlation. Accurate diagnosis of patients with a clinical suspicion of HPP is crucial as not only is the disease life-threatening but the patients may be offered bone targeted enzymatic replacement therapy. © 2017 Wiley Periodicals, Inc.

Clinical Efficacy of Preoperative CT-Assisted Planning for Primary Total Knee Arthroplasty: A Pilot Randomized Clinical Trial.

This study aims to determine the mean posterior condylar angle (PCA) in the included population and its relation to coronal alignment; and to know the clinical importance of the use of preoperative computed tomography (CT) scan in total knee arthroplasty (TKA). We randomized 50 patients with primary knee osteoarthritis into 2 groups. We used CT scan axial images to measure the PCA. In the first group we followed the CT scan plan (group 1), but in the second we did not follow the plan and adjusted rotation to the standard three degrees (group 2). The mean age of the included patients was 63 years. The radiological data of the included patients showed 5 patients with valgus deformity and 45 patients with varus deformity with the mean coronal alignment of 7.5 degrees. CT scan showed the mean PCA of 3.7 degrees (1.3 degrees). The axial knee postoperative X-ray showed the mean patellar tilt angle of 2.1 degrees (0.5 degrees) and 1.9 degrees (0.5 degrees) in groups 1 and 2, respectively. The congruence angle was 4 degrees (2.6 degrees) in group 1 and 5.5 degrees (3.2 degrees) in group 2. The median Knee Society functional score in group 1 was 85 (12), while it was 84 (7.5) in group 2. The median postoperative Western Ontario and McMaster Universities Arthritis Index score in group 1 was 84 (18.6) whereas 80.2 (13.6) in group 2. The median postoperative Bartlett score in group 1 was 30 (5), while it was 30 (6) in group 2. The use of preoperative CT scan did not improve the patient functional scores after TKA.