Integrating Genetic Services in the Philippine Public Health Delivery System: The Value of Networks.

The delivery of genetic services in developing countries is faced with significant challenges, despite medical and technological advances globally. The Philippines, being an archipelago, faces even more challenges, with significant disparities in access to healthcare, and tertiary medical centers and specialists being concentrated in the major cities. The utilization of different networks for the integration of genetic services in the existing public health delivery system has been valuable. Using the well-established network of the national newborn screening program, genetic services have been successfully integrated into the delivery of healthcare, even at the grassroot level. Equitable access to healthcare, including genetic services, was highlighted and supported by the enactment of the Rare Disease Law in 2016. The support of the academe to assure the sustainability of services was evident in the establishment of a genetic counseling program to augment the work of a handful of clinical geneticists. Professional societies and support groups have been instrumental in identifying genetic conditions to be prioritized and lobbying for increased public awareness, leading to national programs and policies. This paper primarily discusses the value of networks in the delivery of genetic services, specifically newborn screening, programs for rare diseases, birth defects, and genetic counseling.

Clinical, Biochemical, and Molecular Characteristics of Filipino Patients with Tyrosinemia Type 1.

Hereditary tyrosinemia type I (HT1), or hepatorenal tyrosinemia, is an amino acid disorder which may cause hepatic failure as well as renal and neurologic comorbidities. Early detection of this disorder is possible with newborn screening (NBS). The objective of this study is to describe the clinical, biochemical, and molecular characteristics of Filipino patients diagnosed with HT1 through the expansion of the Philippine NBS program in 2014. There were a total of 16 patients with confirmed HT1 from then until September 2022. Clinical and biochemical data during confirmation and initial evaluation, as well as molecular data, were obtained from the patients' medical records. The cohort included children between the ages of 18 and 54 months at the time of data collection. The mean age at treatment initiation was 26.8 days. The mean succinylacetone level from dried blood spot sampling using tandem mass spectrometry (MS) was 11.1 µmol/L. Biochemical confirmatory tests via plasma amino acid analysis showed mean levels of tyrosine, phenylalanine, and methionine of 506.1 µmol/L, 111.5 µmol/L, and 125.4 µmol/L, respectively. Upon urine organic acid (UOA) analysis, succinylacetone was detected in all except for one patient, who was managed prior to UOA analysis. The most common clinical characteristics were abnormal clotting times (62.5%), elevated alpha fetoprotein (37.5%), anemia (31.3%), and metabolic acidosis (31.3%). The most common genotype was homozygous c.122T>C p.Leu41Pro in 64.3% of patients. The allelic frequency of this pathogenic variant is 71.4%. The inclusion of HT1 in the Philippine NBS program allowed early diagnosis and management of HT1 patients.

Carnitine-acylcarnitine Translocase Deficiency with c.199-10T>G Mutation in Two Filipino Neonates Detected through Parental Carrier Testing

Carnitine-acylcarnitine translocase deficiency (CACTD), a fatty acid oxidation defect (FAOD), can present in the neonatal period with non-specific findings and hypoglycemia. A high index of suspicion is needed to recognize the disorder. The case is of a 24-year-old G2P2(2000) mother who sought consultation for recurrent neonatal deaths. The neonates, born two years apart, were apparently well at birth but had a fair cry and no spontaneous eye opening within the first 24 h of life and died before the 72nd hour of life. Newborn screening of both babies revealed elevated long chain acylcarnitines and hypocarnitinemia suggestive of a FAOD. However, due to their early demise, no confirmatory tests were done. Parental carrier testing was performed, revealing both parents to be heterozygous carriers of a pathogenic variant, c.199 10T>G (intronic), in the SLC25A20 gene associated with autosomal recessive CACTD. This is the first reported case of CACTD in the Filipino population.

Successful Implementation of Expanded Newborn Screening in the Philippines Using Tandem Mass Spectrometry.

Newborn bloodspot screening (NBS) began as a research project in the Philippines in 1996 and was mandated by law in 2004. The program initially included screening for five conditions, with a sixth added in 2012. As screening technology and medical knowledge have advanced, NBS programs in countries with developed economies have also expanded, not only in the number of newborns screened but also in the number of conditions included in the screening. Various approaches have been taken regarding selection of conditions to be screened. With limited resources, low- and middle-income countries face significant challenges in selecting conditions for screening and in implementing sustainable screening programs. Building on expansion experiences in the U.S. and data from California on Filipinos born and screened there, the Philippine NBS program has recently completed its expansion to include 29 screening conditions. This report focuses on those conditions detectable through tandem mass spectrometry. Expanded screening was implemented in a stepwise fashion across the seven newborn screening laboratories in the Philippines. A university-based biochemical genetics laboratory provides confirmatory testing. Follow-up care for confirmed cases is monitored and provided through the NBS continuity clinics across the archipelago. Pre-COVID-19 pandemic, the coverage was 91.6% but dropped to 80.4% by the end of 2020 due to closure of borders between cities, provinces, and islands.

Successful Implementation of Newborn Screening for Hemoglobin Disorders in the Philippines.

The Philippine newborn bloodspot screening (NBS) program began in 1996 with 24 hospitals and was formalized by legislation in 2004. The NBS panel was recently expanded to include a number of additional hereditary congenital conditions. Expertise and experiences from other NBS programs already screening for hemoglobinopathies were essential to its successful integration into the ongoing dried bloodspot NBS program in the Philippines. Building on clinical experiences and population data from Filipinos born in California, USA, hemoglobinopathies (including thalassemias) were selected for inclusion in the expanded screening panel. Hemoglobinopathy NBS, using high performance liquid chromatography, was implemented in a stepwise manner into the seven regional NBS screening laboratories. A central university laboratory provides confirmatory testing using both capillary electrophoresis and molecular methodologies. NBS results indicating carriers are followed up with educational fact sheets, while results of presumptive disease are referred for confirmatory testing and follow-up with a hematologist. Long-term care is provided through newborn screening continuity clinics across the country. Hemoglobinopathy NBS is now included in the national insurance package and screening uptake continues to increase nationally, exceeding 90% of all newborns in 7400+ hospitals and birthing centers nationwide prior to the COVID-19 pandemic.

Change in bone mineral density of Filipino patients with osteogenesis imperfecta after 6 months of pamidronate therapy In a tertiary hospital in the Philippines

BACKGROUND: Osteogenesis imperfecta is a heritable disorder due to a collagen gene mutation causing a structural abnormality leading to brittle bones and osteopenia. To address the osteopenia, intravenous bisphosphonates (pamidronate) act by temporarily halting the action of osteoclasts giving time for osteoblasts to build bone. To date, there has been no local data regarding the improvement in bone mineral density of filipino patients with osteogenesis imperfecta following treatment. METHODS: This study is a retrospective review that included six patients aged 1 year and 10months-9 years and 9 months old at the Philippines General Hospital with moderate to severe osteogenesis imperfecta who have undergone six months of pamidronate infusions at 1mg/kg/dose monthly or a total dose of 6mg/kg. Chart review was done. Hand radiographs taken at baseline and after six months of therapy were reviewed by radiologist who was blinded, to determine metacarpal indices. RESULT: There was an increasing trend in the metacarpal index from baseline to six months post-treatment with a mean difference of 0.053mm (CI -0.0112 to 0.117). However, the increase was not stastically significant (p value 0.0874) when analyzed using the paired t-test at a 95% confidence interval. No adverse events were noted and only one patient reported a fracture after starting therapy. CONCLUSION: Bisphosphonate infusions among the six pediatric patients with moderate to severe osteogenesis imperfecta are well tolerate and although the increase in the metacarpal index from baseline after six months of treatment is not statistically significant, the trend shows improvement of the osteopenia from baseline.

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.