Studies have shown a dramatic increase in the incidence and the prevalence of chronic diseases such as type 2 diabetes mellitus and cardiovascular disorders over the last several decades. ...Environmental triggers and nutrition are considered major contributors to this increase. The first 1,000 days of life, which is the period between conception and the first 2 years of age, is considered the time for environmental factors, such as nutrition, to exert their positive and most crucial effects on a child's health. Nutrigenomics, the study of how genes and food components interact, looks into diet-altering disease development by modulating processes involved with the onset, progression, and severity of disease. These factors affecting the development of these chronic diseases are thought to be mediated by epigenetic mechanisms, which are heritable and reversible, and carry genetic information without changing the nucleotide sequence of the genome and are also mediated by maternal and postnatal nutrition.
Without intervention, classic galactosemia is a potentially fatal disorder in infancy. With the benefit of early diagnosis and dietary restriction of galactose, the acute sequelae of classic ...galactosemia can be prevented or reversed. However, despite early and lifelong dietary treatment, many galactosemic patients go on to experience serious long-term complications including cognitive disability, speech problems, neurological and/or movement disorders and, in girls and women, ovarian dysfunction. Further, there remains uncertainty surrounding what constitutes a ‘best practice’ for treating this disorder. To explore the extent and implications of this uncertainty, we conducted a small but global survey of healthcare providers who follow patients with classic galactosemia, seeking to compare established protocols for diagnosis, intervention, and follow-up, as well as the outcomes and outcome frequencies seen in the patient populations cared for by these providers. We received 13 survey responses representing five continents and 11 countries. Respondents underscored disparities in approaches to diagnosis, management and follow-up care. Notably, we saw no clear relationship between differing approaches to care and long-term outcomes in the populations studied. Negative outcomes occurred in the majority of cases regardless of when treatment was initiated, how tightly galactose intake was restricted, or how closely patients were monitored. We document here what is, to our knowledge, the first global comparison of healthcare approaches to classic galactosemia. These data reinforce the idea that there is currently no one best practice for treating patients with classic galactosemia, and underscore the need for more extensive and statistically powerful comparative studies to reveal potential positive or negative impacts of differing approaches.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Philippines is a densely populated nation faced with multiple challenges in the healthcare field given its geographic,cultural, and socioeconomic barriers. Due to the geographic limitations of ...medical services in the country, many patientsmust travel a great distance to referral centers. This was further exacerbated by the Coronavirus disease 2019 (COVID-19)pandemic, which spread across the world and upended lives. This pandemic triggered a public health crisis that impactedhealthcare systems, healthcare workers, and communities worldwide. It compounded current difficulties with the provision andaccessibility of medical services, necessitating the employment of alternative methods of providing health coverage. As a result,advanced technological methods for patient diagnosis, monitoring, treatment, and counseling were rapidly implemented.1
Interest in these technological advances began prior to the COVID-19 pandemic, though primarily in developed countries.However, during this global outbreak, telehealth practices – which refer to online health care services provided by all healthcare professions – have seen a rapid increase in popularity.2,3 Telehealth was brought to the forefront in all countries inorder to surmount lockdown constraints, allow continuous provision of health care for patients, and limit exposure to healthsystems and health providers.4
Traditional medical education and training were likewise disrupted during this time, resulting in the incorporationof telehealth into medical education. To reduce the risks associated with more personnel in the hospital, medical studentswere withdrawn from clinical environments during the COVID-19 outbreak. This created an environment of uncertaintyand limited clinical exposure, with concerns surrounding progression through the medical course and training program.5Continuing medical education, which has traditionally been based on clinical knowledge and skills, now requires onlinetechnical communication skills. Innovative services were rapidly developed with health professionals embracing this newtechnological competence, enabling general consultation for patients, remote patient monitoring, and self-directed patientcare, thereby decreasing the burden on health facilities. Digital learning platforms also provided an effective way to address thelearning gaps caused by the pandemic.
The restriction of “in-person” delivery of healthcare services due to the global outbreak has prompted physicians, includingclinical geneticists and genetic counselors, to investigate alternative methods of providing health care to patients. A telehealthinnovation for online delivery of clinical genetic and genetic counseling services is the Philippine General Hospital’s TelegeneticsService. Despite being launched in 2013 to serve genetics patients across the country, this service has since been upgradedand capitalized resulting in patient appreciation for its COVID-19 exposure prevention, increased access, and time and costefficiency. However, the telegenetics service has its limitations.6,7 Despite the expanding scope of telehealth/telegenetics and itsimmediate application, issues such as data/patient privacy, organizational readiness, digital maturity, regulatory impediments,access and acceptance of the technology, geographical and digital disparities, and its integration with traditional medicalservices have emerged.8 Lack of a detailed physical examination is also lost in a virtual visit, with focused questions leading tofragmented, impersonal interactions.
Even when restrictions were lifted, telehealth usage nonetheless remained significantly higher than it had been prior tothe pandemic. This may indicate a shift in public opinion in favor of this innovative medical practice.9 With the expansion of genetic services in the country, there is now a greater need for telegenetics due to the increased demand for clinical genetic andgenetic counseling expertise. Therefore, evidence on the safety and efficacy of this technology in comparison to the traditionalhealthcare delivery approach is required. If the technology has the potential to improve health care, we must guarantee itsavailability in all resource-limited areas. Future efforts should thus focus on establishing solutions to address the aforementionedissues and concerns within our healthcare and education systems, thereby ultimately enhancing the standard of medical care.
Catherine Lynn T. Silao, MD, PhDInstitute of Human Genetics, National Institutes of HealthDepartment of Pediatrics, College of Medicine and Philippine General HospitalUniversity of the Philippines Manila
REFERENCES
1. Keesara S, Jonas A, Schulman K. COVID-19 and Health Care’sdigital revolution. N Engl J Med. 2020 Jun;382:e82. doi: 10.1056/NEJMp2005835.2. Scott R, Mars M. Telehealth in the developing world: current statusand future prospects. SHTT. 2015;3:25-37. doi:10.2147/shtt.s75184.3. Telemedicine: opportunities and developments in member states -Report on the second global survey on eHealth (Global Observatoryfor eHealth Series, 2). Geneva, Switzerland: World HealthOrganization; 2010.4. Patel SY, Mehrotra A, Huskamp HA, Uscher-Pines L, Ganguli I,Barnett ML. Trends in outpatient care delivery and telemedicineduring the COVID-19 pandemic in the US. JAMA Intern Med.2021 Mar;181(3):388–91. doi: 10.1001/jamainternmed.2020.5928.5. Sharma D, Bhaskar S. Addressing the COVID-19 burden onmedical education and training: the role of telemedicine and teleeducation during and beyond the pandemic. Front Public Health2020 Nov;8:589669. doi: 10.3389/fpubh.2020.589669.6. Herlao IAV, Maceda EBG, Abacan MAR, de Castro Hamoy LG,Alcausin MMLB. Telegenetics services in a tertiary hospital: utilityand patient satisfaction. Acta Med Philipp. 2022. doi: 10.47895/amp.vi0.4981.7. Tumulak MJR, Pascua AV, Jover EJM, Guerbo RJ, Canoy GMR,Laurino MY. Genetic counseling in the time of COVID-19: ThePhilippine experience with telegenetics. J Genet Couns. 2021Oct;30(5):1285-91. doi: 10.1002/jgc4.1518.8. Doraiswamy S, Abraham A, Mamtani R, Cheema S. Use of telehealthduring the COVID-19 pandemic: scoping review. J Med InternetRes. 2020 Dec;22(12):e24087. doi: 10.2196/24087.9. Omboni S, Padwal RS, Alessa T, Benczúr B, Green BB, Hubbard I,et al. The worldwide impact of telemedicine during COVID-19:current evidence and recommendations for the future. Connect Health.2022 Jan;1:7-35. doi: 10.20517/ch.2021.03.
Although the exact pathogenesis of subacute sclerosing panencephalitis (SSPE) remains to be determined, our previous data suggested a genetic contribution to the host susceptibility to SSPE. During ...chronic viral infection, virus-specific cytotoxic T lymphocytes display poor effector functions. Since co-inhibitory molecules are involved in the suppression of T lymphocytes, we investigated whether single nucleotide polymorphisms (SNPs) of genes encoding co-inhibitory molecules contributed to a susceptibility to SSPE. Association studies on a total of 20 SNPs in 8 genes (CTLA4, CD80, CD86, PD1, PDL1, PDL2, BTLA and HVEM) and subsequent haplotype analysis of 4 SNPs in the PD1 genes were performed in Japanese and Filipino SSPE patients and controls. Then, we investigated a functional difference in promoter activity of two haplotypes and compared the expression levels of PD1 between SSPE and controls. The frequency of GCG(C) haplotype of PD1 containing −606G allele was significantly higher in SSPE patients than in controls both in Japanese and in Filipinos. The promoter activity was significantly higher in the construct with −606G allele than in that with −606A allele. The expression levels of PD1 were significantly higher in SSPE patients than in the controls. Our results suggested that the PD1 gene contributed to a genetic susceptibility to SSPE.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mucopolysaccharidosis type II, an X-linked recessive disorder is the most common lysosomal storage disease detected among Filipinos. This is a case series involving 23 male Filipino patients ...confirmed to have Hunter syndrome. The clinical and biochemical characteristics were obtained and mutation testing of the IDS gene was done on the probands and their female relatives.
The mean age of the patients was 11.28 (SD 4.10) years with an average symptom onset at 1.2 (SD 1.4) years. The mean age at biochemical diagnosis was 8 (SD 3.2) years. The early clinical characteristics were developmental delay, joint stiffness, coarse facies, recurrent respiratory tract infections, abdominal distention and hernia. Majority of the patients had joint contractures, severe intellectual disability, error of refraction, hearing loss and valvular regurgitation on subspecialists' evaluation. The mean GAG concentration was 506.5 mg (SD 191.3)/grams creatinine while the mean plasma iduronate-2-sulfatase activity was 0.86 (SD 0.79) nmol/mg plasma/4 h. Fourteen (14) mutations were found: 6 missense (42.9%), 4 nonsense (28.6%), 2 frameshift (14.3%), 1 exon skipping at the cDNA level (7.1%), and 1 gross insertion (7.1%). Six (6) novel mutations were observed (43%): p.C422F, p.P86Rfs*44, p.Q121*, p.L209Wfs*4, p.T409R, and c.1461_1462insN710.
The age at diagnosis in this series was much delayed and majority of the patients presented with severe neurologic impairment. The results of the biochemical tests did not contribute to the phenotypic classification of patients. The effects of the mutations were consistent with the severe phenotype seen in the majority of the patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
ABSTRACT
Classic galactosemia is an autosomal recessive disorder caused by deleterious variants in the galactose‐1‐phosphate uridylyltransferase (GALT) gene. GALT enzyme deficiency leads to an ...increase in the levels of galactose and its metabolites in the blood causing neurodevelopmental and other clinical complications in affected individuals. Two GALT variants NM_000155.3:c.347T>C (p.Leu116Pro) and NM_000155.3:c.533T>G (p.Met178Arg) were previously detected in Filipino patients. Here, we determine their functional effects on the GALT enzyme through in silico analysis and a novel experimental approach using a HeLa‐based cell‐free protein expression system. Enzyme activity was not detected for the p.Leu116Pro protein variant, while only 4.5% of wild‐type activity was detected for the p.Met178Arg protein variant. Computational analysis of the variants revealed destabilizing structural effects and suggested protein misfolding as the potential mechanism of enzymological impairment. Biochemical and computational data support the classification of p.Leu116Pro and p.Met178Arg variants as pathogenic. Moreover, the protein expression method developed has utility for future studies of GALT variants.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Classic homocystinuria due to cystathionine β‐synthase (CBS) deficiency is an autosomal recessive disorder of sulfur metabolism. Clinical manifestations include mental retardation, ...dislocation of the optic lens (ectopia lentis), skeletal abnormalities and a tendency to thromboembolic episodes. We present the first mutational analysis of CBS in a Filipino patient with classic homocystinuria.
Methods
Genomic DNA was extracted from peripheral blood collected from a diagnosed Filipino patient with classic homocystinuria. The entire coding region of CBS (17 exons) was amplified using polymerase chain reaction and bidirectionally sequenced using standard protocols.
Results
The patient was found to be compound heterozygous for two novel mutations, g.13995G>A c.982G>A; p.D328K and g.15860‐15868dupGCAGGAGCT c.1083‐1091dupGCAGGAGCT; p. Q362‐L364dupQEL. Four known single‐nucleotide polymorphisms (rs234706, rs1801181, rs706208 and rs706209) were also detected in the present patient's CBS. The patient was heterozygous for all the identified alleles.
Conclusions
This is the first mutational analysis of CBS done in a Filipino patient with classic homocystinuria who presented with a novel duplication mutation and a novel missense mutation. Homocystinuria due to CBS deficiency is a heterogeneous disorder at the molecular level.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In the beginning, medical genetics was concerned only with rare single gene or chromosomal disorders. However, the Human Genome Project has made available information of invaluable diagnostic and ...therapeutic importance. It links the genome with human health.
It is becoming clear that all diseases or medical conditions have a genetic component with a huge proportion of the general population having a recognized genetic disorder. Presently, there is greater appreciation of genetic contributions to normal physiologic processes, early disease detection, pathogenesis, prevention and susceptibility to disease, disease prognostication and monitoring, the development of innovative diagnostic tests and novel therapeutic approaches. Genetics is currently the driving force in medical research.
While the papers in this special 2017 Genetics issue of Acta Medica Philippina give different perspectives on genetics, certain key themes have become evident in the submissions. We highlight birth defects, molecular genetics, cancer genetics, dysmorphology–craniofacial syndromes, the importance of folic acid, metabolic disorders, and genetic counselling issues. With the expansion of our genetic understanding of normal physiologic processes and disease, the role of the genetic counselor has also undoubtedly increased. The challenge is to make these genetic advances benefit people/ patients and the public. There is a need to educate them and make them aware of the different facets of genetics and its implications to the patient, their families and disseminate these information to the community.
The integration of genetics into medical practice will occur at a different pace for all areas in medicine. Genetic technology is available and accessible for everyone with interest to do genetic research in their corresponding medical field.
It is realized though that the Philippines, being a developing country, needs to recognize the burden imposed by genetic disorders and birth defects. There must be political will and commitment to sup port the implementation of these genetic services. Knowledge about genetic disorders and birth defects must be enhanced and the goals of genetic services in terms of both individual/family welfare and public health must be delineated with ethical principles and cultural diversity respected.
Catherine Lynn T. Silao, MD, PhD, FPPS Guest EditorInstitute of Human GeneticsNational Institutes of HealthUniversity of the Philippines Manila
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