PURPOSE:To report interim results from the ongoing, open-label, phase 3 APHENITY Extension Study (NCT05166161), evaluating long-term treatment with sepiapterin in patients with phenylketonuria. METHODS:Participants received an age-based dose of oral sepiapterin daily; those with mean blood phenylalanine (Phe) levels <360 μmol/L (<5.95 mg/dL) after 2 weeks underwent a 26-week dietary Phe tolerance assessment, wherein dietary Phe intake was adjusted and blood Phe levels monitored. Other participants continued treatment with optional diet liberalization. Primary endpoints included change from baseline to week 26 in dietary Phe intake and treatment-emergent adverse events (TEAEs). RESULTS:As of September 2, 2024, 169 participants received sepiapterin (median [minimum, maximum] age: 14.0 [0.2, 55.0] years, median exposure: 72.9 weeks); 102 participants underwent dietary Phe tolerance assessments. Mean (SD) dietary Phe intake increased from 27.6 (18.0) mg/kg/day at baseline to 62.5 (41.5) mg/kg/day at week 26 (least-squares mean change [SE]: 36.4 [2.8] mg/kg/day from baseline) (P < .0001 from post hoc analysis). The incidence of treatment-related TEAEs was 29.0%; 3 participants (1.8%) discontinued treatment owing to treatment-related TEAEs. There were no treatment-related serious TEAEs or deaths. CONCLUSION:Interim results support the long-term safety of sepiapterin and demonstrate the potential for diet liberalization in adults and children with phenylketonuria. CLINICALTRIALS: GOV IDENTIFIER:NCT05166161 (https://www. CLINICALTRIALS:gov/study/NCT05166161; date of registration, December 8, 2021).

BACKGROUND:Cerebrotendinous xanthomatosis (CTX) is a progressive neurometabolic disorder, and chenodeoxycholic acid (CDCA) is the primary treatment that effectively prevents disease progression. However, using CDCA during pregnancy presents clinical challenges due to limited safety data and theoretical concerns about fetal teratogenicity. OBJECTIVE:This study aims to evaluate maternal and neonatal outcomes in genetically confirmed CTX pregnancies and to assess the safety profile of CDCA when used during pregnancy. METHODS:This retrospective, multicenter study included 19 pregnancies in 12 women with CTX. Data were collected on maternal neurological status, pregnancy outcomes, neonatal characteristics, and long-term offspring development. CDCA treatment status during pregnancy was documented, and outcomes were compared. RESULTS:Of the 19 pregnancies, 16 resulted in live births (84.2%), whereas 3 ended in spontaneous abortions-all in a single undiagnosed patient. Among the 5 pregnancies with a prior CTX diagnosis, 4 were treated with CDCA during gestation. No maternal neurological deterioration or fetal malformations were observed in CDCA-treated pregnancies. In contrast, adverse findings, including neurological decline in 1 mother, a case of spina bifida, and cognitive impairment in offspring, were limited to pregnancies without CDCA treatment. No fetal or neonatal complications suggestive of CDCA-related toxicity were detected. CONCLUSION:Our findings support evidence that continuing CDCA therapy during pregnancy in women with CTX is associated with favorable maternal and fetal outcomes, with no clear indications of teratogenicity. Maintaining CDCA treatment appears to contribute to maternal neurological stability.

Background/Objectives: Phenylketonuria (PKU) is a rare autosomal recessive disorder caused by phenylalanine hydroxylase (PAH) deficiency, impairing the conversion of phenylalanine (Phe) to tyrosine. Although early diagnosis and intervention yield excellent outcomes, dietary adherence often declines in adulthood, potentially leading to poor metabolic control and adverse nutritional consequences. This study aimed to evaluate physical activity levels, nutritional status, metabolic control, and anthropometric outcomes in adults with classic PKU, which have not been sufficiently researched in the current literature. Methods: This cross-sectional study included 100 adults with classical PKU (cPKU; baseline phenylalanine levels ≥ 1200 µmol/L) under regular follow-up at the Division of Metabolism, Hacettepe İhsan Doğramacı Childrens' Hospital. Sociodemographic traits and dietary behaviors were evaluated through structured interviews carried out by a dietitian. Dietary intake was assessed by using a 24 h dietary recall method, and nutrient analyses were performed with the Bebis 7.2 software program. Using the short version of the International Physical Activity Questionnaire (IPAQ), physical activity levels were specified, and participants were categorized according to established scoring criteria. Results: A hundred adults with classical PKU took part in the study, including 47 males and 53 females, with a mean age of 23.84 ± 5.41 years; 5% of participants were underweight, 40% had normal weight, 39% were overweight, and 16% were listed as obese. The intake of mean daily energy is 2443.8 ± 384.6 kcal for men and 1822.5 ± 312.7 kcal for women. Carbohydrates contributed approximately 61% of total daily energy intake in both genders, whereas protein accounted for 12-13% and fat for approximately 26-27% of total energy intake; 17% of participants were physically inactive, 40% were minimally active, and 43% met criteria for sufficient physical activity according to IPAQ-based classification. Energy intake, the use of Phe-free protein substitutes, and BMI were significantly higher in the sufficiently active group compared to the low-active group in men, while no significant differences were observed between physical activity groups among women. Conclusions: Adults with classical PKU showed a high prevalence of overweight and obesity, together with differences in dietary intake and physical activity patterns. Physical activity levels were associated with several nutritional and metabolic characteristics; however, further long-term research is required to fully understand these connections.

Abstract:We report a 16-year-old girl with progressive ataxia, gaze palsy, and psychotic symptoms suggestive of Niemann-Pick disease type C (NPC). Despite strong clinical and biochemical evidence, including elevated N-palmitoyl-O-phosphocholine-serine (PPCS or lysosphingomyelin-509 [lyso-SM-509]), conventional genetic testing was inconclusive. RNA sequencing of fibroblasts revealed a homozygous NPC1 intronic variant (c.3246-25A > G) causing aberrant splicing. Miglustat was initiated, leading to clinical stabilization. A systematic literature review identified 12 patients with intronic splice-altering variants located outside the canonical splice donor and acceptor regions, including variants situated more than 20 bp from exon-intron boundaries, predominantly affecting NPC1. Most patients presented with juvenile- or adult-onset disease and showed heterogeneous biomarker profiles. This case highlights the diagnostic utility of RNA sequencing in unsolved NPC cases and emphasizes its role in uncovering cryptic pathogenic variants, enabling timely diagnosis and treatment. Intronic variants should be considered in genetically elusive but clinically compatible NPC presentations.

OBJECTIVES:NSUN3 encodes a mitochondrial RNA methyltransferase responsible for cytosine methylation at the tRNA wobble base, which plays a role in the regulation of mitochondrial translation. Variants in NSUN3 lead to impaired oxidative phosphorylation resulting in multisystem involvement. Reported cases to date have described developmental delay, hypotonia, optic atrophy and neurological involvement. Cardiac manifestations, however, have not yet been clearly associated with NSUN3 deficiency. Here, we report hypertrophic cardiomyopathy (HCM) as a new clinical feature and the long-term follow-up of our case, further expanding the phenotype of NSUN3-related disease. CASE PRESENTATION:An 18-year-old girl was referred for visual loss, progressive fatigue, muscle weakness and HCM. Initial symptoms started as hypotonia in infancy and proceeded with developmental delay, reduced visual acuity and chest pain. At the age 15 years, she was diagnosed with HCM. Cardiac magnetic resonance imaging showed concentric left ventricular (LV) hypertrophy with septal thickness measuring up to 20 mm, LV ejection fraction was preserved (70 %). Whole exome sequencing identified a homozygous likely pathogenic variant in the NSUN3 gene: NM_022072.5: c.465dup (p.Gly156ArgfsTer6), for which both parents were found to be heterozygous carriers. CONCLUSIONS:To our knowledge, this is the first reported case of NSUN3-related mitochondrial disease with HCM. An increasing number of reported cases will likely contribute to a more comprehensive understanding of the clinical phenotype and genotype-phenotype correlations.

We report two siblings harboring a homozygous MGME1 variant, NM_052865.4:c.818 T>A; p.(Val273Glu), both presenting with ptosis, myopathy, scoliosis, and gastrointestinal symptoms. The index patient developed progressive, medically refractory dilated cardiomyopathy and underwent successful orthotopic heart transplantation (OHT). Reanalysis of previously negative WES identified the variant in the index case, and segregation by Sanger sequencing confirmed homozygosity in both siblings. Although several clinical findings overlap with previously described MGME1 -related disease, the detected variant remains classified as a variant of uncertain significance (VUS); thus, functional evidence is needed to better understand its potential causal relevance. Additionally, this report underscores the importance of periodic genomic data reanalysis and highlights the variable expressivity that may occur even within the same family.

This retrospective study on X-linked PDHA1-related pyruvate dehydrogenase complex (PDHc) deficiency combined a systematic literature review with a multicentre survey exploring genotypes, phenotypes and survival. Data from 891 individuals (45% unpublished) were included. Of note, 53% of cases were females. Median age at last assessment was 6 years (range 0-80 years, n = 622). We detected 331 different (118 unpublished) PDHA1 variants, of which 75% (305/405) had occurred de novo. Variants in this study were uploaded to ClinVar (SCV006297015-SCV006297345). The 10 most frequent variants accounted for 36% of the diagnoses. Sixty-nine per cent of the variants were private; missense (50%) and frameshift (20%) variants were most common. Frameshift/nonsense (FS/N) variants in males (44/401, 11%) were confined to regions escaping nonsense-mediated decay (NMD) and were significantly less frequent than in females (151/461, 33%). Neonatal or infantile (405/529, 77%) presentations were most frequent, with pre/perinatal abnormalities reported in 47% (159/342). FS/N variants in the NMD-predicted region 3.9 [95% confidence interval (CI) 1.54-11.04] times increased the odds of fetal findings. Females presented significantly earlier [2 months, interquartile range (IQR) 7.0, n = 224] than males (8 months, IQR 16.6, n = 233), with increased risk of neonatal presentation [odds ratio (OR) 3.01 (95% CI 1.279-7.616)] when harbouring FS/N variants in the NMD-predicted region. The overall (n = 242) mean survival time was 10.9 (95% CI 9.9-11.9) years. On average, females survived 4.5 (95% CI 2.62-6.40) years longer than males despite presenting more severe phenotypes. Poor survival was associated with male sex [hazard ratio (HR) 3.3 (95% CI 1.95-5.62)], neonatal presentation [HR 5.5 (95% CI 2.17-14.09)], FS/N variants in the NMD-predicted region [HR 4.0 (95% CI 1.78, 9.16)] and splice variants [HR 2.3 (95% CI 1.15, 4.59)]. More severe clinical phenotypes were predicted by neonatal or infantile presentations and by female sex. Developmental delay (DD), intellectual disability (ID), muscle hypotonia, abnormal movements, seizures, feeding difficulties and microcephaly were the most frequent phenotypes, all occurring in more than half. Corpus callosum or basal ganglia alterations and cerebral atrophy were common. Four per cent (36/891) were reported to have mild phenotypes with no DD nor ID (25/36 males). This is the largest dataset on a nuclear-encoded defect of mitochondrial energy metabolism. The genotypic and phenotypic details further defines the disease landscape and can be used for variant interpretation. The correlations between genotypes, sex, phenotypes and survival, adds substantial improvement to counselling.

Background. Scientific congresses are critical platforms for knowledge dissemination and collaboration. The scientific value of presented abstracts is best demonstrated through their subsequent publication as full-text articles in peer-reviewed journals. This study aimed to evaluate the publication rate and characteristics of oral abstracts presented at the Turkish National Pediatric Congresses (TNPC) between 2019 and 2023. Methods. Abstract books of five consecutive congresses were reviewed. The publication status of each abstract was determined through systematic searches in Web of Science, PubMed, Scopus, Google Scholar and the TR Index utilizing the title, keywords from the title and author names. Parameters such as study design, collaboration type, index status and the impact factor of the journal, the year it was published, and time to publication were analyzed. Additionally, the subspecialty of each abstract and the publication rate for each subspecialty were evaluated. Results. Among 268 oral abstracts, 111 (41.8%) were published as full-text articles. Of these, 66 (59.5%) were published in journals indexed in the Science Citation Index Expanded. Approximately one-third (32.4%) of the articles were published in Q1 or Q2 ranked journals. The average impact factor was 1.72 ± 1.26 and the mean time to publication was 1.6 ± 1.17 years. The most common study design published was retrospective (51.3%), and the majority were single-center studies (88.3%). The highest publication rates were observed in the fields of rheumatology, adolescent medicine, and infectious diseases. Conclusion. A significant portion of the papers presented at TNPC congresses are published in peer-reviewed scientific journals. The fact that more than one-third of the published studies appear in high-impact journals demonstrates the academic quality of the papers presented at the congresses and the effectiveness of the selective evaluation process. The findings provide valuable contributions to the monitoring and development of academic productivity in the field of pediatrics in Türkiye.

The evolving field of fetal neurology can offer insights into early nervous system development through antenatal dynamic ultrasonography and maternal perception of movements. The spectrum of abnormal fetal movements ranges from fetal akinesia, often associated with arthrogryposis multiplex congenita (AMC), to increased repetitive movements, typically indicating fetal seizures. Nonepileptic hyperkinetic movement disorders of the fetus are rarely documented. Here, we report a female infant who had clonus-like movements in utero and postnatally. Antenatal ultrasonography revealed polyhydramnios, fetal growth restriction, and repetitive clonus-like movements (∼5 Hz), which the mother perceived as frequently "shaking" her. The infant required resuscitation and intubation at delivery. AMC, ectrodactyly, cataract, axial hypotonia, and absent primitive reflexes were noted, along with persistent high-frequency, low-amplitude clonus-like movements without accompanying ictal epileptic activity on the EEG. Laboratory findings included markedly elevated serum creatine kinase levels attributed to sustained contractions, severe neutropenia, and 3-methylglutaconic aciduria. Despite supportive care, she died of respiratory failure on day 15. Whole-exome sequencing established the diagnosis as caseinolytic peptidase B deficiency, an autosomal recessive primary mitochondrial disorder caused by pathogenic variants in the nuclear-encoded CLPB gene. This is a unique case of AMC, paradoxically occurring with hyperkinesia rather than with global hypokinesia, but the hyperkinetic movement repertoire is limited and restrictive. This case underlines the diagnostic value of integrating antenatal history and imaging with detailed postnatal phenotyping by a multidisciplinary team in neurometabolic disorders.

Objectives Propionic acidemia (PA) is an autosomal recessive multisystem disorder caused by the deficiency of propionyl-CoA carboxylase, encoded by PCCA and PCCB genes. This retrospective study presents the clinical and laboratory characteristics of PA patients followed up in our center. Methods Included in the study were 50 patients diagnosed in a single center with propionic acidemia between 1984 and 2020, whose electronic and written hospital records regarding demographic, clinical, and laboratory features, along with diagnostic and therapeutic approaches, were reviewed retrospectively. Results This cohort had a median age at diagnosis of 18 days and 91.1 % (n=41) were born at term. Consanguinity was notably prevalent (91.1 %), and a family history of PA was reported in 14 % of cases. No significant relationships were observed between clinical and laboratory parameters and mortality. Laboratory findings at the time of diagnosis revealed significant metabolic abnormalities, including low levels of free carnitine, elevated C3 propionyl carnitine, and varied amino acid imbalances. Twenty-three patients exhibited developmental delay and/or intellectual disability. Brain magnetic resonance imaging unveiled white matter involvement and ventricular dilatation in 9/25 patients. Furthermore, dilated cardiomyopathy (26 %) was noted in patients who had cardiac assessments. Among the study cohort, 27 patients survived, 23 patients died during follow-up. No significant relationships were observed between clinical and laboratory parameters and mortality. Conclusions Despite improvements in the understanding of the pathophysiology and advances in diagnostic and treatment approaches, propionic acidemia and its long-term complications can still lead to severe consequences. This comprehensive evaluation offers valuable insights into the multifaceted nature of PA.

OBJECTIVES:Newborn screening and childhood immunization are among the most successful public health initiatives. Turkey has a high vaccination coverage (95-99%), but a recent decline is concerning. Vaccine hesitancy (VH) is a growing global issue, identified by the WHO as a major public health threat. Given that VH may correlate with attitudes toward other health practices, we explored whether early engagement with the health system via newborn screening influences childhood vaccine acceptance. Although these programs are implemented separately but concurrently as part of the national healthcare system in Turkey, integrating newborn screening and immunization initiatives may increase vaccine uptake through early engagement and trust building. This study aims to evaluate the relationship between newborn screening and parental vaccine hesitancy. METHODS:This study was conducted at a tertiary care center in Turkey from July 2023 to April 2024. Parental VH was assessed using the PACV scale, along with questions on demographics and parental vaccination status. Participants with PACV score ≥ 50 were classified as VH+, others as VH-. Groups were compared using t-tests, Mann - Whitney U, chi-squared, or Fisher's exact tests. Multiple logistic regression was used to analyze related factors. RESULTS:This analytic descriptive study included 481 parents (125 with children diagnosed with biotinidase deficiency or PKU via newborn screening, and 356 with healthy children aged 2-6). The mean age of respondents was 35 years, and the majority were mothers with a college education. The main sources of vaccine information were health professionals, followed by social media and family. Overall, 19.8% of parents were vaccine-hesitant, with a lower rate in the patient group (12% vs. 22.5%). VH was higher in fathers with chronic diseases (35.1% vs 18.1%, p = .012) and was lower in mothers received tetanus vaccine during pregnancy (16.1% vs. 30.6%, p = .001) or parents who received COVID-19 vaccine (mothers: 13.9% vs. 50.6%, fathers: 14.8% vs. 49.2%, both p < .001). VH was lower in those consulting healthcare professionals and higher in those relying on social media or non-medical sources. Diagnosis and treatment through newborn screening had an effect of 0.47 odds on VH in the overall group (95% CI = 0.24-0.92, p = .028). CONCLUSION:This study found lower vaccine hesitancy among participants in newborn screening programs and those whose parents received adult vaccinations, potentially due to increased contact with health professionals and greater health-seeking behavior. The influence of social media on vaccine hesitancy, evident in the general population, was not observed among cases, suggesting that systematic follow-up may buffer against external risk factors. Studies with matched cohorts, real-time data collection, and anonymous surveys are needed to improve generalizability, support causal inference, and reduce biases.

Objective: Despite overlapping features, these 2 groups of disorders may exhibit distinct clinical and biochemical profiles. This study aimed to evaluate and compare the clinical presentation, laboratory findings, neuroimaging characteristics, genotypic spectrum, and clinical outcomes of patients with ketogenesis and ketolysis defects. Materials and Methods: Thirty patients diagnosed between 1986 and 2023 were retrospectively reviewed. Diagnosis was confirmed by clinical findings, biochemical, and genetic/enzymatic testing. Data included demographic details, clinical manifestations, neurodevelopmental status, laboratory results, imaging findings, genetic information, and treatments. Results: Of the 30 patients, 13 (43.3%) were diagnosed with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD), 14 (46.7%) with 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD), and 3 (10%) with succinyl-CoA:3-ketoacid CoA transferase deficiency (SCOTD). Patients with ketolysis defects presented at a later median age (210 vs. 30 days, P < .009) and exhibited more profound metabolic acidosis (pH 7.06 ± 0.18 vs. 7.26 ± 0.12, P = .028). Common presenting symptoms included vomiting in 25 (83.3%), hypoglycemia in 9 (33.3%), and seizures in 5 (16.6%). Leigh-like neuroimaging findings were observed in 3 HMGCLD patients. Biallelic pathogenic variants in HMGCL, ACAT1, or OXCT1 were identified in 14 patients. Dialysis was required in 1 MATD and 1 SCOTD case. Excluding those lost to follow-up, the mortality rates among the remaining 18 patients were 1/8, 12.5% in 2/9 HMGCLD, and 22.2% in MATD. One of the patients with SCOTD was alive at the time of the last follow-up. Conclusion: Patients with ketolysis defects are more likely to present later and with severe metabolic acidosis, occasionally requiring renal replacement therapy. Delayed diagnosis may hinder timely intervention, potentially contributing to increased mortality.

Cerebrotendinous xanthomatosis (CTX) is a treatable neurometabolic disorder. Chenodeoxycholic acid (CDCA) is the first-line treatment and can potentially halt disease progression if initiated before neurologic symptoms appear. This nationwide, multicenter study evaluates the long-term effects of treatment in 86 genetically confirmed patients with CTX receiving CDCA for ≥ 6 months, focusing on neurologic and extraneurologic outcomes, prognostic factors, and biochemical response. Clinical and biochemical parameters were recorded at baseline and follow-up, and neurological outcomes were assessed using neurological disability scores. Our results indicate a critical age of 28 years for the start of treatment. Patients diagnosed before 28 years showed 100% neurological stabilization or improvement, whereas patients diagnosed later had a higher rate of disease progression (p < 0.05). CDCA effectively stabilized or improved pyramidal and cerebellar symptoms, although myoclonus and parkinsonism remained less responsive. Psychiatric symptoms showed a lower treatment response, with psychosis being the most refractory finding. CDCA resulted in a strong and sustained reduction in cholestanol levels, although biochemical response did not always correlate with clinical improvement. Longer diagnostic delay and presence of anxiety and pyramidal/cerebellar symptoms were associated with poorer outcomes. Notably, a cholestatic child, for whom liver transplantation had initially been considered, recovered completely under CDCA therapy. Our results show that early diagnosis and initiation of CDCA therapy significantly improve neurological outcomes in CTX. However, even in late-diagnosed patients, treatment continues to be beneficial, demonstrating that it is never too late to start therapy. Biochemical response does not always predict clinical improvement; multidisciplinary follow-up is essential.

Background: It has been reported that phenylalanine (Phe)-restricted diets may have negative effects on bone health in patients with classical phenylketonuria (cPKU). We aimed to evaluate bone mineral density (BMD) in adults with cPKU and determine the risk factors associated with low BMD. Methods: Eighty adult patients with cPKU were examined, including 41 women and 39 men. The age range was 18.3-39.4 years (median 22.8). The femoral and lumbar BMD were measured by dual energy X-ray absorptiometry. The patients were evaluated in two groups with low (Z-score <=-2) and normal BMD (Z-score > -2). Results: Low BMD was detected in 20 patients (25%). The low BMD group had significantly more males (75% vs 40%, p < 0.01) and lower mean body mass index (BMI, 22.4 vs 24.5 kg/m2, p = 0.02). Paradoxically, mean blood calcium and 25-hydroxy vitamin D levels were higher in the low BMD group, but only marginally (10.0 vs 9.8 mg/dl and 25.1 vs 21.0 g/L respectively, p < 0.05). The groups did not differ significantly with regards to age, mean Phe levels at diagnosis, median Phe levels above the age of 12 years, other nutritional parameters or vitamin-mineral supplementation. There was no history of clinical fractures. Discussion: Although osteopenia, osteoporosis and low BMD have been reported in PKU, conflicting data also exist. Our study of a large adult cPKU cohort strongly supports previously published limited data that suggest male sex and low BMI confer a higher risk for low BMD in cPKU; and age, Phe levels and dietary adherence do not. In our study, although the patients were young, low BMD was quite common (25%). Bone health should be evaluated even in young adults with cPKU, especially in males and those with low BMI, regardless of treatment compliance and vitamin-mineral status. Prospective studies reporting on clinical outcomes such as bone pain or fractures will be valuable in the coming years.

BACKGROUND:Phenylketonuria is an autosomal recessive disorder characterized by the deficiency of phenylalanine hydroxylase, which converts phenylalanine into tyrosine. Diagnosis and prompt initiation of appropriate treatment shortly after birth are important for achieving optimal outcomes in phenylketonuria. IDMP-PKU is an ongoing study to gain insight into the patient journey and identify the unmet needs and areas for improvement in diagnosis, treatment, and follow-up of PKU in Türkiye. AIM:To present the rationale and design of the IDMP-PKU study, as well as the findings from an interim analysis, describing baseline demographic, diagnosis, family history, and genetic testing data for 1553 children enrolled in the study. METHOD:This is a multicenter, observational registry-based study, conducted in 3 tertiary pediatric metabolic clinics in Türkiye. The study provides a descriptive analysis of baseline demographic, diagnosis, family history, and genetic testing data of study population. RESULTS:The study included 1,553 patients (median age: 10 (IQR 5-18) years; 37.1% classical PKU) from 90% of the cities in Türkiye, diagnosed between 1981 and 2022. Parental consanguinity was reported in 43.5% of families (27.1% first cousins). The most frequently detected allelic variant was c.1066-11G > A (IVS-10-11G > A) (22.8%). Homozygous mutations were more common in patients with parental consanguinity (76.8% vs 17.1%; p < 0.001). The median time to diagnosis improved to 21 days after the implementation of the national newborn screening (NBS) program in December 2006 but 28.6% of patients were diagnosed after one month of age. Low level of maternal education was associated with longer time to diagnosis (p < 0.001). CONCLUSIONS:Implementation of national NBS has contributed to earlier identification of patients with PKU. Increasing the number of screening laboratories and pediatric metabolic clinics will speed up the diagnostic process and help achieve the guideline-recommended time for diagnosis and initiation of treatment. In countries with high rates of consanguineous marriages, increasing public awareness of PKU and genetic counselling before marriage will be valuable in reducing the prevalence of PKU.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder characterized as deficiencies in phenylalanine hydroxylase, leading to neurotoxic effects and neurodevelopmental challenges. Sleep, crucial for cognitive and behavioral development, remains underexplored in PKU populations. This study evaluates sleep characteristics and influencing factors in school-aged children with PKU compared to those with hyperphenylalaninemia (HPA) and healthy controls. A total of 101 children aged 5–10 years participated: 37 with PKU, 31 with HPA, and 33 healthy controls. Sleep quality and disturbances were assessed using the Children’s Sleep Habits Questionnaire (CSHQ) and parent-reported data. Additional factors, including phenylalanine levels and sleep hygiene practices, were analyzed. Despite no significant differences in total CSHQ scores across groups, children with PKU exhibited unique patterns, such as being less likely to awaken by himself or herself. Phenylalanine levels showed no significant correlations with overall sleep characteristics, except for an association with reduced sleep anxiety. Distinct sleep hygiene influences emerged in the HPA and control groups, while no such relationships were observed in PKU. This study underscores the complexity of sleep disturbances in PKU, highlighting the need for future research integrating biological, behavioral, and environmental factors. Identifying determinants of sleep problems will aid in developing tailored interventions to enhance the quality of life for patients with PKU.

OBJECTIVES:Glutathione synthetase deficiency (GSSD) is a rare, autosomal recessive disease that causes disruption in glutathione metabolism. According to clinical findings, it occurs in three forms: mild, moderate and severe. In severe forms, metabolic acidosis and hemolytic anemia are accompanied by neurological findings. Although there is no definitive treatment, early initiation of sodium bicarbonate, vitamin C, and vitamin E supplements is one of the most important factors affecting prognosis. CASE PRESENTATION:Here we present a severe case of GSSD in a neonate with intrauterine periventricular cystic lesions, and postnatally developed severe hemolytic anemia, metabolic acidosis, and dilated cardiomyopathy. Exchange transfusion and peritoneal dialysis were performed because of refractory hyperbilirubinemia and acidosis despite sodium bicarbonate and vitamin supplementation. CONCLUSIONS:Early diagnosis and initiation of supportvive treatment with sodium bicarbonate, vitamin C, and vitamin E are esential for survival in severe GSSD. Dilated cardiomyopathy may represent a new complication of disease, highlighting the need for early cardiac monitoring.