Critical congenital heart disease (CCHD) is a major cause of neonatal morbidity and mortality. Pulse oximetry screening enables early detection, potentially reducing complications and improving outcomes. This study evaluated pediatric residents’ knowledge, attitudes, and practices (KAP) related to CCHD screening in Saudi Arabia. A cross-sectional survey was distributed to pediatric residents across Saudi Arabia. The questionnaire assessed knowledge, attitude, and practice regarding CCHD screening. A total of 123 pediatric residents in training were included in the study. Of these, 57 (46.3%) were male, and 66 (53.7%) were female. A progressive increase in mean scores was observed with advancing training years (p = 0.010). A significant difference was observed in knowledge scores based on completion of a cardiology rotation (p = 0.006). A progressive increase in attitude scores was observed with each successive year of training. Current year in training showed a statistically significant association with attitude scores (p < 0.001). Completion of a newborn nursery or NICU rotation was also significantly associated with higher attitude scores (p = 0.027). Similarly, attitude scores were significantly higher among those who had completed a cardiology rotation (mean = 12.99, SD = 1.52) compared to those who had not (mean = 11.60, SD = 1.84; p < 0.001). While practice scores were not statistically different across most groups, senior residents demonstrated better adherence to screening. Residents exhibit increasing awareness and positive attitudes with experience; however, practical implementation remains inconsistent. Targeted education and standardized protocols are necessary to improve outcomes. A positive correlation was observed between knowledge and attitude scores (r = 0.346, p < 0.001).
Functional analysis of SLC22A5 variants can improve diagnostic accuracy in patients with primary carnitine deficiency (PCD). Herein, we performed a genetic analysis of three neonates with PCD. Two of the patients harbored a novel synonymous SLC22A5 variant that has not been previously reported, and the other patient harbored a classical splice site variant. The splicing patterns of the two SLC22A5 variants were evaluated using three in silico tools, and in vitro minigene analysis was performed to verify the impact of variants on RNA splicing mechanisms. All three in silico tools predicted that both SLC22A5 variants could alter normal RNA splicing. Functional studies using minigene assays demonstrated that the c.450C>T (p.F150=) leads to partial exon 2 skipping, and c.394-1G>A leads to intron 1 retention and exon 2 skipping. Intron 1 retention of 65 nucleotides and exon 2 skipping were confirmed by sequencing cDNA amplification products. These results, along with functional evidence, led to reclassification of c.450C>T (p.F150=) and c.394-1G>A as likely pathogenic and pathogenic, respectively. This is the first reported synonymous variant in the SLC22A5 gene that has been functionally validated to affect RNA splicing, thus enriching the variant spectrum of SLC22A5 and aiding accurate PCD diagnosis.
CFTR modulators have transformed the clinical evolution of patients with CF. The number of pregnancies is increasing in women with CF, most of whom are now treated with CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) or Tezacaftor/Ivacaftor. This raises some questions as we still lack data on foetal and maternal safety. The preliminary data seem to support the continuation of modulators. Some of these mothers may also give birth to newborns with CF and this raises more questions. We report here four cases of CF newborns whose mothers were treated with CFTR modulators throughout pregnancy to help refine potential foetal outcomes of in utero administration of CF modulators. No maternal or foetal complications could be attributed to CFTR modulators. Three CF newborns were exposed to ETI and were false negative of the newborn screening. Two of them were pancreatic sufficient at birth. The remaining patient, exposed to Tezacaftor/Ivacaftor (TI) alone, showed elevated immunoreactive trypsin (IRT) and severe pancreatic insufficiency at birth. These cases highlight that in utero administration of ETI could potentially improve neonatal outcomes of CF newborns and cause newborn screening false negative.
Screening for spinal muscular atrophy (SMA) was adopted by all US state newborn screening programs between 2018 and 2024; by the end of 2022, 48 states were screening for SMA. We assessed trends in health insurance records of SMA diagnoses to quantify improvements in the timeliness of SMA identification following the adoption of screening. We used nationally representative Medicaid claims data for approximately half of US births covered by public insurance and a convenience sample of employer-sponsored health plans. We analyzed records for birth cohorts with at least 1 full year of follow-up (i.e., through the end of the following calendar year). For 2017 births, 1.3 per 100,000 infants had SMA codes first recorded by 1 month of age; this increased to 6.6 per 100,000 among publicly insured newborns born in 2022. The rollout of SMA newborn screening across US states was also followed by improvements in the timely detection of SMA. The proportion of infants with SMA detected by 1 month increased from 18% in 2017 to 61% in 2021 and is projected to reach 75% in 2022. Growth in timely detection was even greater in the employer-insured sample. Timely diagnosis of SMA can enable the initiation of treatment prior to the irreversible loss of motor function.
In 2023, the Russian Federation expanded its national newborn screening (NBS) program from 5 to 36 conditions, 29 of which are inherited metabolic diseases (IMDs). This study presents the first nationwide results and outcomes of the expanded NBS program. Between January 2023 and December 2024, dried blood spots from 2,466,615 newborns (98.53% of the birth cohort) were analyzed for IMDs using MS/MS. Screen-positive cases were referred to the national reference center for confirmatory testing, which included biochemical (MS/MS and GC-MS) and genetic analyses (NGS). A total of 41,728 neonates (1.69%) screened positive, of whom 37,733 underwent confirmatory testing. It resulted in 834 confirmed diagnoses of IMDs (1 in 2900 live births). Phenylketonuria was the most prevalent IMD (n = 538; 1 in 4600), followed by MCADD (n = 99; 1 in 25,000). Distinct regional and ethnic variations were observed, including a high prevalence of tyrosinemia type 1 in the Chechen Republic and MCADD in North Ossetia. The integration of NGS was essential for resolving complex cases, such as identifying heterozygous carriers and dual diagnoses. These findings underscore the program’s clinical utility, highlight unique epidemiological patterns, and identify challenges such as false positives and diagnostic complexities, which will guide future refinements.
Mucopolysaccharidosis type I (MPS I) results in the accumulation of glycosaminoglycans (GAG) and, for the purposes of newborn screening, is differentiated into two forms: severe (Hurler syndrome) versus attenuated (encompassing Scheie and Hurler-Scheie syndromes). MPS I was added to the federal Recommended Uniform Screening Panel for newborn screening (NBS) in 2016, and as of December 2025, 45 of 54 programs in the United States (US) screen for MPS I. Within the newborn screening program, a second-tier analysis of GAG is thought to reduce false-positive rates, particularly through mitigating the detection of pseudodeficiency. However, there have been some concerns that the use of second-tier GAG analysis might inadvertently result in missed detection of attenuated cases. A survey of all US NBS programs was conducted requesting data on the total number of screen-positive NBS results for MPS I as well as the final diagnostic outcome from these results. Diagnostic outcomes after screening were classified as false-positive, pseudodeficiency, severe MPS I, attenuated MPS I, and MPS I of undetermined phenotype. Additionally, information on testing methodologies and dates of MPS I NBS implementation was collected. Responses were obtained from 32 NBS programs. The cohort of screening programs utilizing second-tier blood spot GAG determinations detected a higher proportion of severe cases than those not using this second-tier test (48% vs. 29%). The proportion of attenuated cases remained consistent between both groups (13% vs. 14%). The proportion of pseudodeficiency detection was only slightly lower in the cohort using second-tier GAG analysis (85% vs. 91%). Second-tier GAG analysis appears to reduce the detection of false-positive cases and improves the resolution of severe MPS I cases, though the proportion of pseudodeficiency was only slightly lower compared to the programs that do not use second-tier GAG analysis. Currently, the proportion of attenuated cases is comparable between the two cohorts, but the higher number of “undetermined phenotype” cases may eventually shift the balance toward states not using GAG analysis once the type is determined.
Organic acidemias (OADs) are a group of inherited metabolic disorders with a high false-positive rate in newborn screening. In this study, we aimed to evaluate the clinical performance of next-generation sequencing (NGS) as a combined genetic test for OADs. From September 2022 to August 2025, 154,634 newborns underwent primary screening using tandem mass spectrometry (MS/MS). Among them, 151 neonates with suspected OADs underwent combined genetic screening using a pre-designed NGS panel. Of these, 55 cases tested positive on genetic screening, and 17 were ultimately diagnosed with OADs, yielding a prevalence of 1 in 9096. The positive predictive value of NGS was 30.91% (17/55). The genotypes of nine patients (9/17, 52.9%) were identified through NGS screening. Notably, one case of methylmalonic acidemia that would have been missed by MS/MS screening was successfully identified using the combined genetic screening. Additionally, 37 neonates with positive biochemical screening results were confirmed to be either carriers or unaffected individuals. Two cases of Wilson’s disease were also identified through combined genetic screening. Therefore, integrating NGS into conventional MS/MS-based screening can significantly reduce the false-positive rate and shorten the time from screening to definitive diagnosis. This approach provides a valuable model for improving the efficiency and accuracy of newborn genetic screening.
Newborn screening (NBS) is a well-established public health program that enables early detection and treatment of rare disorders in newborns, preventing severe complications or death. Despite its recognized importance, the scope and implementation of NBS programs vary across Southeastern (SE) and Central Europe. This study aimed to evaluate the current status of NBS in 16 countries of SE and Central Europe and assess progress since the previous survey in 2021. A structured questionnaire was distributed to national experts between April and December 2025, collecting data on program organization, coverage, diseases included, laboratory methods, confirmatory testing, consent practices, and future expansion plans. All countries reported universal screening for congenital hypothyroidism, except Kosovo, where a national NBS is in the process of being established. Expanded NBS using tandem mass spectrometry was available in Austria, Bulgaria, Croatia, Cyprus, Greece, Hungary, North Macedonia, Romania, and Slovenia. Spinal muscular atrophy screening became universal in Austria, Croatia, Hungary, Serbia, and Slovenia. Most countries reported plans for further expansion, with congenital adrenal hyperplasia, severe combined immunodeficiency, spinal muscular atrophy, and cystic fibrosis being the most frequently targeted conditions. Although notable infrastructural progress has been achieved, financial constraints, lack of staff, and organizational barriers remain key challenges. The study’s assessment of program effectiveness was further limited by the absence of region-wide systems for capturing end-to-end performance indicators, such as the age of the infant at treatment initiation or missed cases. Regional collaboration and adoption of best practices are therefore vital to ensure equitable access and continuous advancement of NBS programs.
Spinal muscular atrophy (SMA) is a rare neuromuscular disorder causing progressive muscle weakness. Severe SMA forms are typically observed up to six months postnatally. Disease-modifying therapies provide significant benefits, making newborn screening (NBS) essential for timely diagnosis and treatment initiation. The NBS programme evaluated infants born between April 2023 and October 2024 in the Campania region, Italy. DNA was amplified to detect homozygous deletion of the SMN1 gene by RT-PCR and SMN2 copy number using multiplex ligation-dependent probe amplification. Following treatment, motor functions were assessed using CHOP-INTEND and Bayley III scales. Among 62,801 infants screened for SMA, thirteen (11 females, 2 males) tested positive. The distribution of SMN2 copy numbers was as follows: eight patients had two copies, one patient had three, and four patients had four copies. One year after treatment, motor outcome data were available for four of the eight patients with two SMN2 copies. Among these patients, one achieved the milestones of walking without support, and three were standing with support. At 24 months, three of these patients were walking independently. Pre-symptomatic treatment markedly improves motor function development. This underscores the urgent need for large-scale newborn screening to prevent diagnostic delays and ensure timely, effective therapy. Validated care protocols must be established to facilitate early diagnosis and intervention.
In The Netherlands, preventive child healthcare (PCHC) has been carrying out neonatal hearing screening in well-babies since 2006. The aim of this study was to examine the relationship between the age of newborns and the false positive referral rate of the first hearing screening using a transient evoked otoacoustic emission (OAE) test, to identify the most efficient timing for OAE screening. Additionally, we investigated the relationship between the type of OAE screening device (Echoscreen (ES)I/II versus ESIII) and the referral rate during the first screening. We used data from the Dutch universal well-baby neonatal hearing screening programme by PCHC between 2013 and 2023. Multilevel logistic regression analyses were performed to estimate the probability of a referral in 2023 for newborns screened in 2022 and 2023. We included a total of 1,650,506 newborns for 2013-2022 and 323,194 newborns for 2022-2023. The lowest false positive referral rates were found between days five and thirteen, ranging from 3.3 to 3.9%. ESIII significantly increased the probability of a referral compared to ESI/II (odds ratio = 1.84, 95% confidence interval = 1.65-2.06). In conclusion, the timing of neonatal hearing screening significantly impacts the false positive referral rate. Furthermore, the likelihood of a referral is significantly higher when using the ESIII compared to the ESI/II.
Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder caused by bi-allelic deletions or pathogenic SMN1 variants. Early diagnosis through neonatal screening is essential for timely therapeutic intervention, significantly improving clinical outcomes. In August 2022, a pilot neonatal screening program for SMA was launched in Romania, aiming to assess feasibility and impact. Objectives are to present the preliminary results of the ongoing SMA neonatal screening pilot program in Romania, evaluating its effectiveness in early detection and referral for treatment. The program started in August 2022 with four maternity hospitals and has progressively expanded to 28 maternity hospitals nationwide. Dried blood spot samples from newborns were analyzed for SMN1 gene deletions using real-time PCR. Positive results were confirmed through genetic testing, and affected infants, along with their families, were referred for further medical evaluation and early therapeutic intervention. Approximately 60,000 newborns have been screened since the program’s inception, and 12 newborns tested positive for SMN1 deletions, resulting in an estimated incidence rate of 1 in 5125 live births. All confirmed cases were promptly referred for specialized care, with early access to disease-modifying therapies. The program has faced challenges in logistics, parental awareness, and equitable access to treatment, but its expansion from 4 to 28 maternities demonstrates increasing feasibility, suitability, and acceptance. Conclusions: The Romanian pilot neonatal screening program for SMA has successfully identified affected infants early, proving its feasibility and clinical impact. The ongoing expansion suggests a strong foundation for a future national program, which could significantly improve early SMA diagnosis and patient outcomes in Romania.
The aim of the evaluation was to gather information on parents' experiences and attitudes towards the Irish National Newborn Bloodspot Screening Programme (NNBSP). An interviewer-administered survey was completed by 151 parents whose babies underwent newborn bloodspot screening (NBS) between 2023 and 2025 and for whom the screening result was normal. Results suggest that NBS is highly acceptable to parents, with 100% glad their baby underwent screening. The majority (95%) felt they were provided the information needed to understand the importance of NBS for their baby, and 93% are in favour of screening for more conditions. Positive aspects of NBS reported by parents included the following: blood sampling being undertaken in the home, the sample-taker being very nice and being advised in advance to keep the baby's heel warm to ease the sampling process. Negative aspects of NBS reported included the following: having to return to the hospital for sampling, the baby becoming distressed, not receiving adequate information and not receiving the screening results. Parents were more likely to report negative experiences if the sample was not taken at home and if the sample was taken by a healthcare professional other than a public health nurse. Parents offered recommendations for improvements to the programme. This study provides important insights into parents' experiences and attitudes towards NBS in Ireland.
Spinal muscular atrophy (SMA) is a genetic condition that causes the degeneration of motor neurons in the spinal cord. Newborn blood spot (NBS) screening can potentially enable diagnosis before symptoms, and presymptomatic treatment is considered to be more effective than symptomatic treatment. In this paper, we present an overview of a cost-effectiveness model of NBS screening for SMA in the UK, informed by key clinical trials and the relevant published literature. Our analyses suggest that implementing screening could result in better outcomes and lower costs compared to the current approach of no screening plus treatment. However, several uncertainties and limitations of the model remain. These include uncertainty in the reimbursement status of nusinersen and risdiplam in the future; the 'actual' costs of treatments, as they are under confidential commercial agreements; uncertainty in the long-term effectiveness of presymptomatic and symptomatic treatment; and uncertainty around the incidence of SMA and the costs and the accuracy of NBS screening. An SMA in-service evaluation (ISE) that could capture data specific to the UK is under consideration, and an appropriately designed ISE with ongoing data collection could support periodic updates of clinical and cost-effectiveness estimates of NBS screening for SMA in the UK.
In the Netherlands, the newborn screening (NBS) program includes screening for propionic aciduria (PA) and methylmalonic aciduria (MMA). When initial screening reveals elevated C3 concentrations or abnormal ratios (C3/C2, C3/C16), a second-tier test measuring methylcitric acid (MCA) for PA and methylmalonic acid (MMAmb) for MMA is performed. While this two-tier approach reduces false positives effectively, it can delay referral from the NBS program and diagnosis of propionic aciduria. We describe four early-onset PA cases in which the current Dutch screening algorithm negatively impacted clinical outcomes, highlighting the need for expedited referral. We investigated different alternative screening strategies to identify the most effective approach for improving timeliness, while maintaining the high specificity of Dutch PA NBS. This revised approach prioritizes the evaluation of the C3/C2 ratio in first-tier screening. Specifically, samples with a C3/C2 ratio ≥ 0.75 should be referred directly for medical consultation and confirmatory testing. For all other samples with less pronounced biochemical abnormalities, the existing two-tier screening algorithm remains an appropriate NBS protocol. To position our approach internationally, a survey of European NBS programs was conducted to compare screening and referral protocols for PA across the region.
3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD) is a metabolic disorder with a wide clinical spectrum ranging from asymptomatic individuals to severe metabolic decompensation. Following the introduction of expanded newborn screening, a high number of asymptomatic individuals with 3-MCCD were identified, prompting debates about its inclusion in screening panels. In order to inform policy and healthcare decisions regarding the inclusion of 3-MCCD in newborn screening programs, we evaluated the long-term outcomes for newborns with positive results over a decade of screening experience in North-East Italy, as well as the psychological impact on their parents. Of the 336,668 newborns screened between 2014 and 2025, 9 were confirmed to be affected. These infants underwent annual clinical and biochemical assessments, including dried blood spot acylcarnitine profile, plasma free carnitine, and urinary organic acids assays. An emergency protocol was provided to all affected children to manage intercurrent illnesses. An ad hoc survey was developed to assess the psychological impact of the disease on parents. During follow-up (mean age at last visit: 4.2 years), one patient experienced metabolic decompensation during an intercurrent illness, which was promptly treated. One patient presented with growth retardation and another with transient psychomotor delay. Five patients developed carnitine deficiency, requiring supplementation. Psychological assessments revealed an initial high level of parental psychological impact, which decreased over time. All parents strongly supported the screening program. Newborn screening for 3-MCCD enabled the early identification and management of affected individuals, thereby avoiding severe metabolic decompensation. Although there is an initial psychological burden on parents, it significantly decreases over time. Therefore, the long-term benefits of newborn screening for 3-MCCD seem to outweigh the psychological drawbacks.
The German federal state of Bavaria implemented newborn screening (NBS) using dried blood spots (DBS) as an integrated public health programme with centralised coordination. The Bavarian NBS Centre collaborates with NBS laboratories, obstetric and paediatric facilities, specialised centres of expertise, and parents. It is responsible for coordination, evaluation, quality assurance, and a long-term follow-up study. In this paper, an analysis of NBS in Bavaria from 1999 to 2023 and a long-term follow-up for the birth cohort until 2013 is presented. Of the 2,854,190 babies screened, 2500 were diagnosed and treated early thanks to NBS. An NBS coverage rate of 99.83% was achieved, with 99.09% of all requested repeat tests completed. Around 87% of infants with time-sensitive conditions underwent a clinical intervention within the first 14 days of life. Systematic tracking enabled all but 54 NBS-positive results to be clarified and 122 newborns to be diagnosed in due time. The results of the long-term follow-up study demonstrate that almost all the children identified through NBS receive ongoing medical care, and that NBS has contributed to the age-appropriate development of most affected children. This 25-year evaluation of NBS in Bavaria shows that near-universal participation in NBS and follow-up of almost all positive NBS results can be achieved through centralised coordination and ongoing cooperation of all those involved.
This study was designed to assess the effectiveness of neonatal congenital adrenal hyperplasia (CAH) screening in Guangzhou, China. A total of 818,417 newborns were screened for CAH by measuring 17-hydroxyprogesterone (17-OHP) concentrations. Cut-off values were stratified based on gestational age (GA) and the timing of sample collection. Neonates with initial positive results (17-OHP ≥ cut-off value) were recalled for a second dried blood spot sample to reassess 17-OHP levels. Confirmatory testing involved biochemical analyses, Sanger sequencing, and multiplex ligation-dependent probe amplification of the CYP21A2 gene. From 2018 to 2024, a total of 40 patients with classical 21-hydroxylase deficiency were identified, including 28 cases (70%) of the salt-wasting form and 12 cases (30%) of the simple virilizing form. The overall incidence of CAH was 1 in 20,653 (95% confidence interval: 1:34,928, 1:14,661). No statistically significant differences in prevalence were observed between sexes or between preterm and full-term infants (p > 0.05). 17-OHP concentrations are influenced by GA and the timing of sample collection. The screening efficiency for CAH could be improved by adopting a multitiered cut-off value system adjusted for GA and collection time.
This study aims to investigate the genotype characteristics of newborns with biallelic GJB2 mutations and their correlation with hearing phenotypes, providing a basis for clinical genetic counseling and hearing management. A retrospective study was conducted on 652 newborns with biallelic GJB2 mutations detected at the Newborn Diseases Screening Center of Shenzhen Maternal and Child Health Care Hospital from January 2022 to December 2024. The differences in mutation types, hearing screening, and diagnostic results were analyzed and compared between the homozygous and compound heterozygous mutation groups to assess their correlation with hearing phenotypes. Genotype analysis identified 543 cases of homozygous mutations, mainly the c.109G>A/c.109G>A genotype (98.90%). Compound heterozygous mutations were identified in 109 cases, with the majority being c.109G>A/c.235delC (76.15%). Following two-stage hearing screening, 227 (34.82%) of the 652 cases were referred, with bilateral failure accounting for the majority (81.94%) of these cases. The referral rates showed no significant difference between the homozygous (35.54%) and compound heterozygous (31.19%) groups (p > 0.05). The overall hearing loss detection rate was 6.90% (45/652); among these, eight infants who had initially passed the newborn hearing screening were later found to have hearing loss between 2.5 and 6 months of age. Among the 45 confirmed deaf children, hearing loss was mainly mild to moderate (87.50%), and profound deafness was only seen in the homozygous mutation group (10.29%, 7/68 ears). Most newborns with biallelic GJB2 mutations passed the two-stage hearing screening, and associated hearing loss was typically mild to moderate. Long-term auditory monitoring remains essential for all genetically confirmed infants to monitor late-onset progression.
Following Newborn Screening (NBS), parents receiving positive results experience various psychosocial effects upon learning their child’s genetic information or unexpected findings. These factors warrant careful consideration. The Japanese Medical Association’s Guidelines for Genetic Testing and Diagnosis in Medical Care highlight the importance of genetic counseling (GC) in NBS; however, its current implementation status remains unclear. This study aimed to determine current approaches to GC following positive NBS results in Japan. A questionnaire was conducted with pediatric metabolic specialists responsible for treating individuals who screen positive through NBS results to evaluate GC implementation and their views on its provision. GC was provided at most referral centers for NBS (although not routinely at approximately half of the facilities). In over 70% of cases, GC was performed by a metabolic specialist, regardless of clinical geneticist certification. Furthermore, some metabolic specialists may be reluctant to provide GC due to limited understanding or time constraints. Raising awareness that all parents are eligible for GC, regardless of their child’s diagnosis or health status, is essential. In addition, a GC system incorporating multidisciplinary and multidepartmental collaboration is important for the multifaceted support of patients and families.
This study evaluates the incidence of metabolic disorders detected from January 2005 to December 2024 and their clinical outcomes. Data were retrospectively collected from the Louisiana Newborn Screening database. Clinical outcomes were obtained through review of corresponding medical records. In addition, an electronic questionnaire assessing educational attainment and neurodevelopmental disorders was sent to the patients’ families. Of 1,230,356 infants screened, 478 were diagnosed with metabolic disorders, corresponding to an incidence of 1 in 2574 live births. The three most commonly identified conditions were biotinidase deficiency, phenylketonuria (PKU), and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). During the study period, at least 11 patients died. The program demonstrated a false-positive rate of 0.93%. Twelve patients (7%) were symptomatic before or at the time of NBS result notification. Recurrent metabolic decompensations occurred in 3 of 4 maple syrup urine disease (MSUD) cases, 7 of 7 methylmalonic acidemia (MMA) cases, 1 of 4 propionic acidemia (PA) cases and 1 of 7 urea cycle defect cases. Regarding long-term outcomes, 45.7% of survey respondents reported adverse neurodevelopmental outcomes of varying severity. Early detection and timely intervention have contributed to normal or near-normal outcomes in many cases. However, the morbidity and mortality observed in some patients despite early diagnosis highlights the severity and complexity of certain metabolic conditions. Additionally, the relatively high false positive rate underscores the need for ongoing efforts to improve the specificity of screening protocols to reduce unnecessary follow-ups and mitigate potential stress for families.
