Mitochondrial respiratory chain disorders have very diverse manifestations and can present with any symptom, in any organ at any time. Here we describe two Filipino children confirmed to have a mitochondrial respiratory chain disorder after presenting with non-specific neurologic symptoms. The first patient had Otahara syndrome and was later on found to have complex I deficiency. The second patient had the m.8993T>G mtDNA mutation that was consistent with a Leigh phenotype.
Human ; Female ; MITOCHONDRIAL DISEASES ; NUTRITIONAL AND METABOLIC DISEASES ; METABOLIC DISEASES

There is still a strong need for new treatment strategies that will maintain remission and prolong survival in patients with acute lymphoblastic leukemia (ALL). The glutathione-S-transferase (GST) enzymes, which are coded by highly polymorphic genes, have been associated with the risk of developing cancer and were found to regulate effect of cancer treatment drugs.
OBJECTIVES: The present study determines the association of GSTM1, GSTP1 and GSTT1 polymorphisms and treatment response in terms of occurrence of adverse events and relapse in ALL in Filipino children.
METHODS: This is a follow up study on the 2007 investigation done by Alcausin et al. which determined the association of the GST P1, M1, and T1 polymorphisms and occurrence of ALL. Four-year follow-up data were available for 46 out of the 50 patients from January 2007 to May 2011. Odds ratios (OR) as measures of association of GST M1, P1 and T1 gene polymorphisms with treatment outcomes were estimated at 95% confidence interval.
RESULTS: Results show a trend towards predisposition to elevation of liver enzymes in patients with GSTT1 and GSTP1 mutant genotypes showing an OR (95% Cl) of 2.0 (0.62-6.49). The presence of GSTM1 null genotype showed a trend towards protection from occurrence of relapse basing on both crude and adjusted ORs, 0.58 (0.16-2.07) and 0.23 (0.05-1.20), respectively. However, these results are not statistically significant.
CONCLUSION: The GSTP1 heterozygous genotype conferred increased predisposition to elevation of liver enzymes while the GSTT1 null genotype was shown to be a possible risk factor towards the occurrence of both infection and elevation of liver enzymes during chemotherapy. Furthermore, the GSTM1 null genotype appears to be protective from occurrence of relapse. It is recommended to do similar large-scale studies in the future to obtain more conclusive results.

Human ; Male ; Female ; Child ; Child Preschool ; Child ; Confidence Intervals ; Follow-up Studies ; Genotype ; Glutathione ; Glutathione S-transferase Pi ; Glutathione Transferase ; Liver ; Precursor Cell Lymphoblastic Leukemia-lymphoma ; Recurrence ; Treatment Outcome ; Glutathione S-transferase M1 ; Glutathione S-transferase T1

INTRODUCTION: Phenylketonuria (PKU), an autosomal recessive metabolic disorder caused by phenylalanine hydroxylase (PAH) deficiency, leads to hyperphenylalaninemia and neurological damage if untreated. This is the first study in the Philippines to identify the disease-causing mutations in the PAH gene of clinically diagnosed Filipino PKU patients.

METHODS: The study included four unrelated PKU patients detected by the Philippine Newborn Screening Program from 1996 to 2008. Plasma amino acid analyses for all patients showed increased phenylalanine and low to normal tyrosine levels consistent with the diagnosis of PKU. Mutations in the PAH gene were identified by genomic DNA extraction from dried blood spots of the patients, PAH exon amplification by polymerase chain reaction and subsequent bi-directional DNA sequence analysis.

RESULTS: All patients presented with significantly elevated phenylalanine levels on bacterial inhibition assay and thin layer chromatography. Urinary pterins confirmed the diagnosis of Tetrahydrobiopterin deficiency in two patients while the other 2 patients had the Classical PKU phenotype. Four previously identified mutations in the PAH gene (p.I65T, p.R413P, p.EX6-96A>G, p.R243Q) were identified in those with Classical PKU.

CONCLUSION: The present results confirm the heterogeneity of mutations at the PAH locus in Filipinos. Neonatal screening and the use of molecular diagnosis significantly aid in the medical management and genetic counseling of patients and their families.

Phenylalanine Hydroxylase ; Phenylalanine ; Neonatal Screening ; Genetic Counseling ; Tyrosine ; Pterins ; Chromatography, Thin Layer ; Philippines ; Phenylketonurias ; Exons ; Sequence Analysis, Dna ; Phenotype ; Dna

Introduction. Birth defects are global problem with impact particularly severe in middle - to low -income countries. In the Philippines, there is a limited data on birth defects despite the fact that congenital anomalies have been in the top 10 causes of infant mortality. The objectives of the study were: 1.) to determine the occurrence of birth defects among patients admitted to the Philippine General Hospital (PGH); 2.) To present the distribution of patients by geographic location and age group distribution; 3.) To categorize birth defects by organ systems; and 4.) To categorize birth defects as either isolated, part of a recognizable syndrome, chromosomal syndrome of multi-malformed case. Methods. Patients admitted to PGH from 2001-2010 and to have major structural defects were included in this study. Case ascertainment was done through a review of medical records of all admitted patients age 0 to more than 65 years old. Patients with birth defects was assigned codes of International Classification of Diseases (ICD)-10 classification. Results. Of the 438,944 admissions to the PGH from 2001 to 2010, there were 8,686 (2.0%) patients with a diagnosis of at least one (1) birth defect. The most common birth defects are as follows: digestive system (3,605/8,686 or 41.5%), cardiovascular system (,839/8,686 or 32.7%), nervous system (1,070/8,686 or .3%) and genital organ anomalies (755/8,686 or 8.7%). The common digestive system anomalies were cleft lip and /or palate (1,548/8,686 or 17.8%), imperforate anus (698/8,686 or 8%) and hirschsprung disease (582/8,686 or 6.7%). Most of the cardiovascular system anomalies were congenital malformations of the cardiac septa (1,160/8,686 or 13.4%) and the great arteries (769/8,686 or 8.9%), while almost of the nervous system anomalies were due to congenital hydrocephalus (347/8,686 or 4%), encephalocoele (303/8,686 or 3.5%) and spina bifida (193/8,686 or 2.%) The most common genital organ anomalies were hypospadias (340/8,686 or 3.9%) and undescended testicle (233/8,686 or 2.7%) Majority (4,042/8,686 or 46.5%) of birth defect cases came from the National Capital Region (NCR) while 32.5% (or 2,87/8.686) of the cases came from region IV-A or Cavite, Laguna, Batangas , Rizal and Quezon (CALABARZON) Region. Conclusion. The results of this study show that the most common birth defects are digestive, cardiovascular, nervous system, and genital organ anomalies. This trend is similar to those reported internationally. The findings of the study can be the basis of policies toward the development and implementation of practical strategies for primary and secondary prevention of birth defects among Filipinos.
Human ; Male ; Female ; CONGENITAL ABNORMALITIES ; CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES ; ABNORMALITIES ; EPIDEMIOLOGY

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.
Human ; Male ; Female ; Child ; Child Preschool ; PAMIDRONATE ; OSTEOGENESIS IMPERFECTA ; MUSCULOSKELETAL DISEASES ; BONE DISEASES ; BONE DISEASES, DEVELOPMENTAL ; BONE DISEASES, METABOLIC ; OSTEOCHONDRODYSPLASIAS ; THERAPEUTICS ; THERAPY ; OSTEOPOROSIS

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.
Human ; Male ; Female ; CONGENITAL ABNORMALITIES ; CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES ; EPIDEMIOLOGY

Mosaic trisomy 13 is estimated to occur in 5% of all trisomy 13 cases. Presentation of trisomy 13 mosaicism is highly variable, with cases that may present with a normal phenotype and intellectual function, to cases with grossly abnormal features and profound developmental delays. We present a 2-year-old female with trisomy 13 mosaicism, who presented with small for gestational age (SGA), polydactyly, ventricular septal defect (VSD), and poor oral feeding.
Trisomy 13 Syndrome ; Genetic Counseling

Polymorphisms in metabolic genes have been shown to modulate susceptibility to oral cavity cancer. Cases (n=176) and controls (n=317) from the Filipino population were genotyped for selected polymorphisms in CYP1A1, GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subjects. The CYP1A1m1/m1 genotype is protective against oral cancer, while being homozygous for the GSTP1 c.313G genotype and heterozygous for the NAT1*10 homozygotes and non-homozygotes for the CYP1A1 m1 allele. The risk from heterozygosity for the NAT1*10 allele was limited to subjects who were not homozygous for the GSTP1 c.313G genotype remained a significant oral cancer risk modifier, together with environmental variables, the homozygous GSTP1 c.313G genotype remained a significant oral cancer risk modifier, together with environmental risk factors, such as smoking, passive smoking, inverted smoking and tobacco chewing, and environmental protective factors, i.e. moderate consumption of fish sauce (patis) and shrimp paste (bagoong). The GSTP1 c.313G polymorphism increases susceptibility for oral cavity cancer in the Filipino population.

Cyp1a1 Protein, Human ; Cytochrome P-450 Cyp1a1 ; Tobacco Smoke Pollution ; Alleles ; Smoking ; Homozygote ; Ointments ; Protective Factors ; Glutathione Transferase ; Mouth Neoplasms ; Diet