Introduction: Glutaric Aciduria Type 1 (GA1) is an inborn error of metabolism included in the expanded newborn screening of the Philippines. This inborn error of metabolism is caused by glutaryl-CoA dehydrogenase deficiency which is important in the catabolism of lysine, hydroxylysine and tryptophan. Objective: This paper aimed to present the baseline data of patients with GA1 in the Philippines by describing the clinical, biochemical, and radiologic characteristics of Filipino patients with biochemically-confirmed GA1 seen at the Philippine General Hospital from January 2010 to December 2017. The cases of this condition have been increasing and are expected to increase even more with the full coverage of the expanded newborn screening. Methods: This study was a review of the medical records of the GA1 patients managed by the Division of Clinical Genetics, Department of Pediatrics of the Philippine General Hospital (PGH). Biochemical parameters, developmental assessment, neurologic assessment, and radiologic features of the patients were reviewed and analyzed. Results: There were a total of 7 patients with GA1 at the PGH from January 2010 to December 2017. Of the 7 patients, 4 were diagnosed by expanded newborn screening (ENBS) and 3 patients had disease onset prior to diagnosis. Clinical features noted in screened patients include global developmental delay (75%), seizures (50%), dystonia (50%), truncal hypotonia (25%) and macrocephaly (25%). In unscreened patients, macrocephaly was present in 66.67 %, while the other clinical features were present in all of them. Four of the 7 patients had infection and one had vaccination, which may have led to a metabolic crisis and subsequent onset of symptoms. The plasma levels of glutarylcarnitine (C5DC) range from 2.81 to 4.58 umol/L. Grossly elevated urinary excretion of glutarylcarnitine were noted in all patients. Urinary glutaconic acid and 3-hydroxyglutaric acid were also detected in all patients. Both striatal and extra-striatal abnormalities were present in screened and unscreened patients on neuroimaging. The most common being the widening of the sylvian fissure, cerebral atrophy, and white matter abnormalities. Conclusion Although newborn screening of GA1 and initiation of early management of this condition have been seen important, it is still prudent to continue the appropriate management and to provide timely aggressive emergency treatment in order to improve outcome of patients with GA1. With the recent Philippine Health Insurance (PhilHealth) coverage of the expanded newborn screening, it is expected that physicians will encounter more of the metabolic disorders, including GA1. Hence, it is important that physicians be more aware of the presenting signs and symptoms of this disorder, as well as its management, which can further improve the neurologic and developmental outcomes of these patients.
Neonatal Screening

Background: Universal newborn hearing screening is mandated in the Philippines through the Universal Newborn Hearing Screening and Intervention Act of 2009 (RA 9709). Newborn hearing screening (NBHS) centers are required to perform screening tests, compile and submit data on screened newborns, and advise parents on the subsequent steps after NBHS. Objective: The study aimed to conduct a survey of the implementation of the Universal Newborn Hearing Screening and Intervention Program (UNHSIP) in the different regions of the country; and assess the information technology (IT) capabilities of hearing centers. Methods: Fifty-one NBHS centers across twelve regions were surveyed through on-site inspections in 2016. Data was gathered on the centers’ testing capability, staffing, access to specialists, use of local protocols, connectivity, and IT capabilities. Results: All surveyed centers followed the recommended protocols of the Manual of Operations of the Universal Newborn Hearing Screening and Intervention Act of 2009 (RA 9709). Among the 12 regions visited, only five (41.67%) had Category C centers with confirmatory testing and early amplification services as recommended. Majority of facilities (96.1%) were staffed by trained and certified personnel. A small percentage had access to subspecialists such as clinical audiologists (39.2%) and speech-language pathologists (23.5%). All facilities had computer access, but only 58.8% had internet access. Majority (94.1%) of the centers visited were not using the recommended data submission methods, specifically the use of registry cards and the online registry. Only 27.5% of centers had data on newborns who underwent confirmatory testing or early intervention. Conclusion Facilities were found to be compliant to NBHS screening protocols and majority complied with certification requirements for staff; but were found to be non-compliant with use of registry cards or the online registry. Majority of centers were able to contact the parents of neonates who did not pass newborn screening, but had no system to track outcomes. Lack of confirmatory and early intervention services in identified areas emphasize the need for development of regional centers. It is recommended that measures to improve the utilization of the online registry are taken.
Neonatal Screening

Background: With the increasing coverage of the newborn screening (NBS) program in the Philippines, the number of patients being followed-up has also been increasing. The NBS continuity clinics (NBSCCs) have continuously been creating strategies to improve long-term patient health outcomes. Objective: This paper aimed to describe the establishment of a community-based networking system of satellite clinics. Methodology: A document review of resources including powerpoint presentations, a local ordinance, Newborn Screening Reference Center database of statistics of the NBSCCs from 2015 to 2021 and a Department of Health - Center for Health Development memorandum was done. Results: NBS satellite clinics were developed as a strategy for improving the tracking and long-term follow-up of patients confirmed for one of the conditions in the NBS panel. Satellite clinics offering long-term follow-up services were set up in hospitals strategically located in the provinces of the Western Visayas, especially in areas with a high number of patients. Capacity building activities were initiated among the established NBS satellite clinic core teams which were composed of doctors, nurses, and/or midwives. A total of 15 satellite clinics spread out across the six provinces of Western Visayas were established in 2017. By the end of 2020, the Western Visayas region had a total of 528 confirmed patients endorsed by the Newborn Screening Center Visayas (NSC V) and the recall rate increased from 62.77 % in 2015 to 87.79 % in 2020. Conclusion The establishment of satellite clinics provided a region-wide accessibility and availability of longterm follow-up services to the patients as seen by the increase in the patient recall rate. The benefits were seen especially during the implementation of strict border controls due to the pandemic which ensured the continuity of care of the patients in the region. This concept can serve as a model for other NBSCCs in the archipelago and for other regions across the Philippines.
Neonatal Screening

Newborn screening (NBS) facilitates the early diagnosis and management of congenital metabolic disorders that, if left untreated, may lead to mental retardation or death. Successful medical interventions can bring about normal growth and development of individuals with these disorders.1 Introduced by the Newborn Screening Study Group in 1996, NBS became a routine procedure for newborns in the country through the enactment of Republic Act 9288, or the Newborn Screening Act of 2004,1 with the DOH as the lead implementing agency. The law mandates that all birthing and health facilities must offer NBS, in effect making the procedure accessible to all. The law further stipulates that these birthing and health facilities should be given NBS services and support, thus newborn screening centers (NSCs) were created and located strategically throughout the Philippines. An NSC is a facility equipped with a NBS laboratory that complies with the standards established by the National Institutes of Health - Philippines and provides all required laboratory tests and recall/follow up programs for newborns with heritable diseases.1 Currently, there are seven NSCs in the country. The Newborn Screening Center-Mindanao (NSC-Mindanao), the third NBS center to be built in the country, was established at Southern Philippines Medical Center (SPMC; formerly Davao Medical Center) in 2009 under the stewardship of Dr. Leopoldo J. Vega, then SPMC Chief of Hospital. Headed by Dr. Conchita G. Abarquez, NSC-Mindanao acquired its DOH accreditation and started operations in the same year of its establishment. The NSC-Mindanao started with a workforce of 11 staff, consisting of a full-time unit head, a pathologist as laboratory manager, a program manager, three medical technologists, a follow-up nurse, an encoder, an accountant, an administrative officer and an information technology staff. NSC-Mindanao initially performed screening tests for five disorders, namely, congenital hypothyroidism, congenital adrenal hyperplasia, galactosemia, phenylketonuria, and glucose-6-phosphate dehydrogenase deficiency. In its first year of operation in 2009, NSC-Mindanao received and tested 4,187 NBS samples. Screening for maple syrup urine disease was added to the original five tests in 2012. Presently, NSC-Mindanao caters to 1,859 NBS facilities in the six administrative regions in Mindanao—Zamboanga Peninsula (Region IX), Northern Mindanao (Region X), Davao (Region XI), Soccsksargen (Region XII), Caraga (Region XIII), and the Bangsamoro Autonomous Region in Muslim Mindanao (BARMM). As of 2022, NSC-Mindanao employs a workforce of 47 staff,2 consisting of a unit head, a laboratory head, a follow-up head, a laboratory manager, a program manager, 13 medical technologists, three nurse genetic counselors, two follow-up nurses, three project development officers (one medical technologist and two nurses), four nurse demo/encoders, one certified public accountant, two information technology staff, and 14 administrative support staff. All medical personnel are licensed and have completed training on their respective fields of expertise. The NSC-Mindanao laboratory is equipped with modern and top-of-the-line laboratory equipment for NBS. It uses fully-automated neonatal screening platforms, such as AutoDELFIA automated fluoroimmunoassay machines and Genetic Screening Processor machines, for testing endocrine disorders and cystic fibrosis. The center also has several tandem mass spectrometry machines, such as Xevo TQD and TQD Acuity, for screening metabolic disorders, and high-performance liquid chromatography machines for screening hemoglobinopathies. Presently, under the Expanded Newborn Screening Program, NSC-Mindanao tests for 29 panel disorders, including galactosemia, glucose-6-phosphate dehydrogenase deficiency, cystic fibrosis, and biotinidase deficiency, as well as specific endocrine disorders, amino acid disorders, fatty acid disorders, organic acid disorders, urea cycle defects, and hemoglobinopathies. As NBS is essentially a battery of screening tests, positive results need to be confirmed either through repeat collection or various confirmatory tests. Patients with one or more positive test results are recalled by the NSC, the respective health facilities where they were screened, or by their respective DOH regional Centers for Health Development (CHDs), either for repeat specimen collection or for confirmatory testing. The NSC-Mindanao Follow-up Teamㅡcomposed of the Unit Head, the Follow-up Head and five Follow-up Nursesㅡmanages the care of patients with confirmed disorders. The center handles the short-term follow-up of the patients, and provides free medicines and medical supplements to indigent patients. The Newborn Screening Continuity Clinics in SPMC, Cotabato Regional Medical Center, Northern Mindanao Medical Center, and Zamboanga City Medical Center, handle the long-term follow-up of patients with confirmed disorders in Mindanao.3 NSC-Mindanao also provides genetic counseling to patients with confirmed disorders and to their families. A clinical geneticist and three duly-qualified genetic counselor nurses carry out the counseling sessions. NSC-Mindanao, in coordination with the DOH CHDs, also provides NBS training and technical assistance to the NBS facilities. The center also conducts NBS program review and evaluation of these facilities to ensure that their NBS services are always available and at par with set standards, and regularly holds activities to increase public awareness on NBS. To enhance patient support, NSC-Mindanao organizes and participates in public fora and support group sessions among parents of patients with confirmed disorders. NSC-Mindanao undergoes an annual external audit, performed by the University of the Philippines Manila Newborn Screening Reference Center, the DOH technical arm for the NBS program. The audit ensures that the center’s laboratory complies with the set quality standards and assurance program for NSCs. NSC-Mindanao has also engaged the External Quality Assurance (EQA) program of Taiwan’s Preventive Medicine Foundation as third-party internal quality control for the center’s G6PD quantitative tests. NSC-Mindanao also follows the Centers for Disease Control and Prevention’s Newborn Screening Quality Assurance Program for its Expanded Newborn Screening tests, ensuring that the results generated are accurate and reliable. NSC-Mindanao also renews its DOH accreditation every three years. NSC-Mindanao is applying for ISO 15189 Certification for Medical Laboratories and hopes to obtain it by 2023. NSC-Mindanao also anticipates the opening of another NBS center in Cagayan De Oro City. The new NSC will be housed at the Northern Mindanao Medical Center, its host hospital, and will cater to the NBS services and support needs of birthing and health facilities in Region IX, Region X, and BARMM. NSC-Mindanao and the entire NBS program as a whole have been facing several operational challenges. Persuading birthing and health facilities to consistently screen newborn babies at the ideal age has been a demanding task for the center. Timing is essential to successful NBS. Timely screening will lead to timely medical management, which in turn affects the clinical outcomes of patients with confirmed disorders. Ideally, newborns should be screened within 24 to 48 hours after birth, but many birthing and health facilities perform the screening only on, or even beyond, the 5th day from birth. Arranging for a short specimen transit time has also been challenging for the entire NBS system. Transit time should be within two days upon collection, but NSC-Mindanao still receives specimens beyond five days from collection.1 Nationally, the NBS program has yet to achieve its target of 100% NBS coverage. This has been more challenging since the start of the COVID-19 pandemic. For 2021, the NBS program achieved 70% national coverage. Thirteen years after its establishment, NSC-Mindanao has grown exponentially and has become one of the NSCs, if not the NSC, with the widest coverage of NBS in the country. It is committed to fulfill its important contribution to health care, and it will continue the expansion and improvement of the quality of its NBS services in the years to come.
Neonatal Screening

BACKGROUND: Republic Act 9288 or the Newborn Screening Act of 2004 was enacted. A multi-sector effort towards systematic screening of newborn disorders and built-in systems for subsequent confirmatory tests for positively screened as well as treatment for confirmed cases was likewise implemented. Despite multi-sector efforts and continuous quality improvement mechanisms, national newborn screening coverage remained low for several years.

OBJECTIVE: The study determined factors that influence Newborn Screening (NBS) uptake from various perspectives: mothers, health providers, and program administrators.

METHODS: Framework analysis of NBS program documents, 25 focus group discussions and 37 key informant interviews of mothers, health providers and program administrators were done in purposively selected communities in the Cordillera Administrative Region and Region V.

RESULTS AND CONCLUSIONS: Findings showed the need to disseminate correct NBS procedures, especially upon obtaining positive results. Financing issues were addressed innovatively, but system administrators and health providers required a common understanding of program implementation. Monitoring geographically hard-to-reach areas remained a challenge. Barriers outside the system adversely affected filter cards availability, specimen transport, and release of results. Improved online and paper-based educational campaign, greater local government unit support, streamlined PhilHealth processes, a workload-based manpower complement for monitoring, and continuity clinics to handle positive findings can increase NBS uptake.

Objective: The observed irregularities in the biochemical profile and the limited information on long-term outcomes among patients with Duarte variant (D/G) galactosemia have led to patient management variability. This study examined the molecular characteristics of Filipino patients with presumed variant galactosemia for confirmation of diagnosis. It also aimed to describe the corresponding biochemical, clinical and neurodevelopmental profiles in order to gain a better understanding of the patients with normal galactose metabolites in spite of low to absent GALT activity detected by the local newborn screening program. Methods: Thirteen (13) patients who were presumed to have a variant form of galactosemia by national newborn screening between 2002 and 2010, and who previously underwent physical and neurodevelopmental assessment were included in the study. Repeat clinical, ophthalmologic and neurodevelopmental evaluations were done upon recruitment of participants. Direct sequence analysis of the coding region of the GALT gene was conducted to determine the patients’ genotypes. Results: None of the patients’ genotypes were consistent with Duarte variant (D/G) galactosemia. Their genotypes reflect the normal total blood galactose levels in patients, but were inconsistent with the absent or trace GALT activity. Conclusion Molecular testing for the entire cohort of presumed “variant” galactosemia Filipino patients will provide better profiling of this condition. Re-evaluation and assessment of the current guidelines used by national newborn screening in classifying variant galactosemia are recommended.
Galactosemias ; Neonatal Screening

Newborn screening (NBS) was introduced in the Philippines in 1996. After 12 years of implementation, a review of performance of the NBS facilities shows that there is a wide range of NBS performance from zero to 100%. This paper aims to review the NBS facilities (NSFs) that have at least 90% NBS coverage and to identify the successful strategies that have pushed the high coverage.

Humans ; Infant, Newborn ; Neonatal Screening

Background. Newborn screening (NBS) is a procedure for the immediate detection of genetic, metabolic, and endocrine disorders in neonates and is crucial for prompt treatment should such disorders be identified. In the Philippines, Republic Act 9288 requires health workers to properly inform mothers regarding NBS and its importance before the procedure.

Objective. To determine the knowledge, attitude, and awareness of primiparous postpartum mothers towards NBS Methods: A survey questionnaire was administered to primiparous mothers from Wards 15 and 16 of the Philippine General Hospital from April 11 through May 14, 2017. Results of primiparous postpartum mothers with or without previous prenatal check-ups were then compared.

Results. We surveyed 160 mothers, with half (56.3%) aged between 20 and 29 years. There were 149 mothers with and 11 without prenatal checkups. Mothers with previous prenatal checkups were more likely to be aware of NBS than those without prenatal checkups. Knowledge on NBS of mothers with previous prenatal checkups was higher on average compared to those without previous prenatal checkups. There was no significant difference in attitude between mothers with or without prenatal checkups.

Conclusion. Prenatal checkups increased the awareness and knowledge of primiparous mothers' towards NBS, and thus can be a potent vehicle where healthcare providers may inform the mother on the process and purpose of this procedure.

Cystic Fibrosis (CF) is a rare condition among Asians and has not been reported in the Philippines as of this time. The inclusion of this disease in the Philippines’ Expanded Newborn Screening Program (ENBS) has provided this Filipino family the opportunity of early detection and appropriate management of this condition that could ensure the survival of the proband and his other surviving siblings. Here we present a case of a 24-month-old male who had a positive Expanded Newborn Screening (ENBS) test for cystic fibrosis and eventually underwent further tests to confirm a homozygous deletion of exons 1 - 2 of the CFTR gene. He subsequently had recurrent pneumonia but is being managed by a team consisting of a pulmonologist, gastroenterologist, and a metabolic dietitian. The proband had an older sibling whose Newborn Screening (NBS) test was normal and who eventually expired from recurrent bouts of pneumonia. This sibling was never managed as a case of cystic fibrosis. Implications on the diagnosis and management of CF in the local setting is also discussed. The importance of an appropriate CF panel customized to the local population should be reiterated and carrier testing should be encouraged to help with proper family counseling for future pregnancies for the family involved.
Cystic Fibrosis ; Neonatal Screening ; Philippines