Osteogenesis imperfecta type V: A repost of two Filipino families and review of literature

Osteogenesis imperfecta (Ol) type V is distinct Ol phenotype that has recently been described. Patients with this phenotype present characteristically with interosseous membrane calcification and hyperplastic callus formation. We present the clinical and radiographic characteristics of two Filipino families diagnosed to have Ol type V. Through this review of cases, we aim to educate healthcare providers by highlighting salient clinical and radiographic features to aid in the recognition of this specific Ol phenotype, difficulties in diagnosis, current practices in management and fracture prevention, and issues in genetic counseling.

PMD patient mutations reveal a long-distance intronic interaction that regulates PLP1/DM20 alternative splicing.

Alternative splicing of the proteolipid protein 1 gene (PLP1) produces two forms, PLP1 and DM20, due to alternative use of 5' splice sites with the same acceptor site in intron 3. The PLP1 form predominates in central nervous system RNA. Mutations that reduce the ratio of PLP1 to DM20, whether mutant or normal protein is formed, result in the X-linked leukodystrophy Pelizaeus-Merzbacher disease (PMD). We investigated the ability of sequences throughout PLP1 intron 3 to regulate alternative splicing using a splicing minigene construct transfected into the oligodendrocyte cell line, Oli-neu. Our data reveal that the alternative splice of PLP1 is regulated by a long-distance interaction between two highly conserved elements that are separated by 581 bases within the 1071-base intron 3. Further, our data suggest that a base-pairing secondary structure forms between these two elements, and we demonstrate that mutations of either element designed to destabilize the secondary structure decreased the PLP1/DM20 ratio, while swap mutations designed to restore the structure brought the PLP1/DM20 ratio to near normal levels. Sequence analysis of intron 3 in families with clinical symptoms of PMD who did not have coding-region mutations revealed mutations that segregated with disease in three families. We showed that these patient mutations, which potentially destabilize the secondary structure, also reduced the PLP1/DM20 ratio. This is the first report of patient mutations causing disease by disruption of a long-distance intronic interaction controlling alternative splicing. This finding has important implications for molecular diagnostics of PMD.

The clinical outcome and antibiotic sensitivity pattern of Enterobacter spp. culture positive neonates admitted at Cebu Doctors' University Hospital - Neonatal Intensive Care Unit (2005-2008)

@#Objectives: This aim of this research is to determine the clinical outcome of neonates with Enterobacter spp. positive blood culture and the antibiotic sensitivity pattern of these isolates at Cebu Doctors' University Hospital Neonatal Intensive Care Unit. Methods: This descriptive, cross-sectional, retrospective study retrieved the list of neonates admitted at Cebu Doctors' Hospital - Neonatal Intensive Care Unit (CDUH-NICU) from January 2005 to December 2008 whose bloods were taken for culture. The antibiotic sensitivity patterns of the Enterobacter positive cases were reviewed, along with broad-spectrum cephalosporin (BSC) resistant and multiresistant Enterobacter spp. (MRE) determination and clinical outcome. The relationship between outcome and MRE was analyzed using the Pearson Chi-square test. Conclusion: Most isolates were BSC-resistant while 24% were MRE. Enterobacter was most sensitive to Imipenem, Meropenem, Cefepime, and Piperacillin-Tazobactam.

Intravenous pamidronate treatment in Filipino children with moderate to severe osteogenesis imperfecta

Objective. To present preliminary data on the effects of intravenous pamidronate in children with moderate to severe Osteogenesis Imperfecta (OI). Methods. This is a restrospective study wherein a review of medical records and available serial radiographs of children (N=14) with moderate to severe IO started on pamidronate from 2006 to 2010 was done. Results. Two children have IO Type I, 8 have IO Type III and 4 have IO Type IV. At baseline, 2 had normal height, 8 had height less than minus 2SD and the rest with less than minus 1SD. Twelve out of 14 had vertebral compression fractures. Mean age at start of pamidronate was 5.4 years (range 0.5-11 years). First infusion fever in five patients and transient generalized macular rash in one child were noted. Serum calcium and phosphorus levels were normal at baseline and remained stable. Based on parental report, improvement of motor function was noted. In the 10 children who had at least a year of treatment, long bone fractures decreased from mean annualized fracture rate of 2.6 at baseline to 0.9. In patients with vertebral compression fractures, serial radiographs showed improvement of vertebral shape. Conclusion. This preliminary study shows that treatment was generally well tolerated and led to decrease in long bone fractures, improved vertebral shape and improved function.

Establishment of the Philippine birth defects surveillance

Congenital anomalies have been in the top ten causes of infant mortality in the Philippines for the past 50 years. Since there is no synthetic surveillance for the congenital anomalies in our country, there are no specific programs directed toward better understanding of this group of patients. The birth defects surveillance project was convinced in 008 to develop a system of reporting of newborns with birth defects at the hospital and community setting. The lead agencies for this project are the University of the Philippines Manila-National Institutes of Health and the department of Health (DOH). This paper describes the establishment of the Philippine Birth Defects Surveillance.