A Post-reflective Examination of the Physical and Mental Health Suffering During COVID-19 Through the Lens of Christ's Kenotic and Redemptive Act.

The COVID-19 global pandemic has brought unprecedented physical and mental health challenges to many, making the exploration of the spiritual dimension of suffering increasingly meaningful and relevant. Pope John Paul II's theologico-pastoral approach in Salvifici Doloris (SD) sheds light on how spiritual reflections and pastoral care anchored on the theology of Jesus Christ's sufferings can be put together to contribute to post-COVID-19 reflections. Given this context, this paper explores the perceptions and coping mechanisms of COVID-19 patients as they navigate the challenges of their illness. By examining patient experiences gleaned from medical and scientific journals, the study underscores the necessity of supporting individuals suffering from various diseases. As John Paul II thoughtfully remarks in Salvifici Doloris, there is a profound need to address patients' inquiries about "the cause, the reason, and equally, the purpose of suffering, and, in brief, a question about its meaning." Taking this into account, this paper contextualizes the theology of suffering articulated by Pope John Paul II in SD within the experiences of patients who contracted COVID-19 during the global pandemic. To embark on this discussion, the following themes about suffering are expounded: First, Insights into the Weight of Suffering Among Persons who Contracted COVID-19. Second, Understanding of Suffering in Salvifici Doloris, and Third, The Salvific Meaning of Suffering in COVID-19 and its Transformative Experience.

The Coffin-Siris syndrome: a proposed diagnostic approach and assessment of 15 overlapping cases.

Coffin-Siris syndrome (CSS) is a rare, clinically heterogeneous disorder often considered in the setting of cognitive/developmental delay and 5th finger/nail hypoplasia. Due to the clinical variability of facial and other features, this diagnosis is often difficult to confirm clinically and the existence of this disorder as a specific diagnosis has been at times an issue of debate. In an effort to further delineate the spectrum and key phenotypic features, we reviewed 80 previously reported cases to define features in patients that most closely correlated with a convincing diagnosis. There appear to be two subtypes of CSS, one which displays the "classic" coarse facial features previously described; another displays "variant" facial features which are less striking. Using these features, we defined an algorithm to rank the confidence of diagnosis and applied it to 15 additional patients who had been previously characterized by chromosome microarray. This approach will also facilitate uniform categorization for whole-exome analysis.

Rubinstein-Taybi Syndrome in a Filipino Infant with a Novel CREBBP Gene Pathogenic Variant.

Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder characterized by dysmorphic facial features, broad thumbs and halluces, intellectual disability, and postnatal growth retardation. This report presents a male infant with microcephaly and characteristic facial features, namely, low anterior hairline, hirsutism, thin upper lip and micrognathia, broad thumbs and first toes, cryptorchidism, recurrent pneumonia, developmental delay, and growth retardation. Genetic testing showed a novel pathogenic variant in the CREBBP gene which is consistent with the clinical diagnosis of RSTS.

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.

A review of the clinical outcomes in idursulfase-treated and untreated Filipino patients with mucopolysaccharidosis type II: data from the local lysosomal storage disease registry.

BACKGROUND: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycan (GAG) accumulation, caused by a deficiency of iduronate-2-sulfatase (I2S). Enzyme replacement therapy (ERT) with recombinant idursulfase (IDS), the standard of care, was started in the Philippines in 2017. This study reviewed the clinical outcomes in idursulfase-treated and untreated Filipino MPS II patients who were included in the local Lysosomal Storage Disease (LSD) registry of the Institute of Human Genetics-National Institutes of Health (IHG-NIH) from January 1999 to December 2019. METHODS: A retrospective audit of records of MPS II patients listed in the registry was done. Qualified patients were divided into two cohorts: idursulfase-treated group (patients on enzyme replacement therapy, ERT, for ≥ 6 months) and untreated group. Baseline characteristics, including demographic data, biochemical results, neurocognitive classification, respiratory involvement, mortality, and adverse events, were recorded. Height, weight, cardiac pathology, liver and spleen sizes, six-minute walking test (6MWT), joint mobility, were determined at baseline and at year 1 and 2 of follow up. RESULTS: Forty male patients were included in this review, with only 8 receiving ERT since 2017. The mean age at diagnosis was 6.99 years (SD 4.15; 0.75-20) and mean age at start of ERT was 14.03 years (SD 7.1; 4-21.5), more delayed than previous reports. Eighty percent have early progressive phenotype which was higher than reported average. The early growth pattern differed in our Filipino cohort, but was followed by the expected slowed growth in later years. Improvements in the following endpoints were observed in the treated cohort: height and weight, cardiac disease, liver and spleen sizes, and joint mobility. There were also positive effects on respiratory involvement and mortality rate. Adverse events were consistent with previous reports. CONCLUSIONS: ERT is generally well tolerated and effective in reducing GAG storage and improving clinical endpoints among our Filipino MPS II patients. In untreated patients, typical disease progression was observed.

Maple syrup urine disease associated with nephrotic syndrome in a Filipino child.

A 22-month-old female child with maple syrup urine disease (MSUD) presented with generalised oedema. Diagnostic evaluation revealed nephrotic range proteinuria, hypoalbuminaemia and dyslipidaemia supporting the diagnosis of nephrotic syndrome (NS). Diet, being at the core of the management plan for both MSUD and NS, necessitated regular monitoring and evaluation via dried blood spot collection of leucine. The opposing requirement for total protein for both disorders (that is protein restriction in MSUD and protein supplementation in NS) prompted a careful balancing act of the dietary management. The monitoring, which revealed normal leucine levels on multiple determinations, allowed an eventual increase in dietary protein and daily administration of albumin to address the NS. Dietary protein increase, both in total protein (3.5 g/kg/day) and natural protein (1 g/kg/day) levels, was instituted. It was observed that NS does not trigger leucinosis and allowed easing of protein restriction in MSUD.

Genetic and clinical characteristics of Filipino patients with Gaucher disease.

Gaucher disease (GD) is a lysosomal storage disorder caused by the deficiency of the ß-glucocerebrosidase enzyme due to disease causing mutations in the GBA1 (glucosidase beta acid) gene, leading to the abnormal accumulation of the lipid glucocerebroside in lysosomal macrophages. This is a review of the clinical features and molecular profiles of 14 Filipino patients with GD. Five patients presented with type 1 disease, two had type 2 GD and seven had type 3 GD. The age of onset for all types was between 1 and 2 years of age but there was a delay of 2.2 years from the time of symptom onset to confirmation of diagnosis. Hepatosplenomegaly, anemia and thrombocytopenia were present in most of the patients. Stunting was seen in 64.3% and bone abnormalities were present in 63.6%. The most common mutant allele detected in this cohort was L483P (previously L444P), followed by F252I, P358A and G241R. IVS2+1 G>A, N409S and G416S mutations were reported singularly. There were 3 patients who were found to have N131S mutations and one patient with D257V mutation, mutant alleles that have only been reported among the Filipinos to date. Except for N409S, the mutations found in this cohort were generally severe and were congruent with the severe phenotypes found in most patients. Of the 14 patients, only 6 were able to undergo enzyme replacement therapy which significantly improved the hematologic parameters and decreased the sizes of the liver and spleen but did not consistently improve the growth and skeletal abnormalities nor alleviate the neurological manifestations of our patients with GD. Improved monitoring through recommended modalities for assessments and tools for evaluation should be implemented in order to fully appreciate the severity of the disease and accuracy of the response to treatment.

Challenges in the management of patients with maple syrup urine disease diagnosed by newborn screening in a developing country.

Maple syrup urine disease (MSUD) is a rare inborn error of metabolism resulting from a deficiency in the branched-chain alpha-ketoacid dehydrogenase complex. MSUD has been reported to be the most common inborn error of metabolism in the Philippines. We described all patients with maple syrup urine disease patients diagnosed through newborn screening during its first 2 years of implementation and the challenges encountered during their medical management. There were 24 patients diagnosed with maple syrup urine disease for the 2-year period. All patients needed hospital admission. The most common complication during hospital admission was infection, needing intravenous antibiotics which were given to 21 of the patients. Out of the 24 diagnosed, 16 patients are alive, while eight have died. Several neurologic and non-neurologic complications have been observed during the follow-up of the patients. The common challenges of MSUD management in a low-resource setting identified in this study were late diagnosis, lack of access to metabolic specialists and medical supplies, nosocomial septicemia, and protein deficiency. Aside from early properly timed collection, improvement in other logistical concerns will also help in earlier diagnosis. Mechanisms of transfer of critically ill patients must be improved. Hospitals in difficult-to-reach areas must be equipped to handle critical metabolic cases when transfers are not possible. Newborn screening has been proven to improve outcome in patients with MSUD but the success of the program in preventing disability is also dependent on improvements in other aspects of healthcare.

Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - Hunter syndrome.

BACKGROUND: 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. RESULTS: 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_1462insN[710]. CONCLUSION: 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.

Plasma amino acid and urine organic acid profiles of Filipino patients with maple syrup urine disease (MSUD) and correlation with their neurologic features.

BACKGROUND: Maple syrup urine disease (MSUD) is the most common inborn error of metabolism in the country. The cause of the neuropathology is still not well established although accumulation of branched chain amino acids (BCAA) and alteration in large neutral amino acids (LNAA) as well as energy deprivation are suggested. It is therefore the aim of this study to determine the plasma amino acid and urine organic acid profiles of patients with MSUD and correlate the findings with their neurologic features. METHODOLOGY: Twenty six Filipino patients with MSUD were studied in terms of their plasma amino acid and urine organic acid profiles. Their results were compared with 26 age and sex matched controls. The neurologic features were correlated with the results of the plasma amino acids and urine organic acids. RESULTS: Majority of the patients with MSUD had developmental delay/intellectual disability (88%), speech delay (69%), and seizures (65%). Their amino acid profiles revealed low glutamine and alanine with high levels of leucine, isoleucine, phenylalanine, threonine and alloisoleucine compared to controls (p < 0.05). The urine organic acids showed significantly elevated excretion of the branched chain ketoacids and succinate (p < 0.05). However there were no biochemical markers that correlated significantly with the neurologic features. CONCLUSION: The findings suggest that there could still be altered LNAA metabolism among patients with MSUD when the BCAAs are elevated. Although the biochemical findings were not significantly correlated with the neurologic features, the study showed that prevention and avoidance of neurologic disturbances may still rely primarily on early diagnosis and prompt institution of treatment, along with strict compliance with the dietary regimen and maintenance of good metabolic control over time.