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Objectives: Dihydropyrimidinase deficiency is a rare autosomal recessive disorder of the pyrimidine degradation pathway, with fewer than 40 patients published. Clinical findings are variable and some patients may remain asymptomatic. Global developmental delay and increased susceptibility to 5-fluorouracil are commonly reported. Here we present atrioventricular septal defect as a novel feature in dihydropyrimidinase deficiency., Case Presentation: A four-year-old male with global developmental delay, dysmorphic facies, autistic features and a history of seizures was diagnosed with dihydropyrimidinase deficiency based on strikingly elevated urinary dihydrouracil and dihydrothymine and a homozygous pathogenic nonsense variant in DPYS gene. He had a history of complete atrioventricular septal defect corrected surgically in infancy., Conclusions: This is the second report of congenital heart disease in dihydropyrimidinase deficiency, following a single patient with a ventricular septal defect. The rarity of the disease and the variability of the reported findings make it difficult to describe a disease-specific clinical phenotype. The mechanism of neurological and other systemic findings is unclear. Dihydropyrimidinase deficiency should be considered in patients with microcephaly, developmental delay, epilepsy and autistic traits. We suggest that congenital heart disease may also be a rare phenotypic feature., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Old age, obesity, and certain chronic conditions are among the risk factors for severe COVID-19. More information is needed on whether inherited metabolic disorders (IMD) confer risk of more severe COVID-19. We aimed to establish COVID-19 severity and associated risk factors in patients with IMD currently followed at a single metabolic center., Methods: Among all IMD patients followed at a single metabolic referral center who had at least one clinic visit since 2018, those with accessible medical records were reviewed for SARS-CoV-2 tests. COVID-19 severity was classified according to the WHO recommendations, and IMD as per the international classification of IMD., Results: Among the 1841 patients with IMD, 248 (13.5%) had tested positive for COVID-19, 223 of whom gave consent for inclusion in the study (131 children and 92 adults). Phenylalanine hydroxylase (48.4%) and biotinidase (12.1%) deficiencies were the most common diagnoses, followed by mucopolysaccharidoses (7.2%). 38.1% had comorbidities, such as neurologic disabilities (22%) or obesity (9.4%). The majority of COVID-19 episodes were asymptomatic (16.1%) or mild (77.6%), but 6 patients (2.7%) each had moderate and severe COVID-19, and two (0.9%) had critical COVID-19, both of whom died. 3 patients had an acute metabolic decompensation during the infection. Two children developed multisystem inflammatory syndrome (MIS-C). Long COVID symptoms were present in 25.2%. Presence of comorbidities was significantly associated with more severe COVID-19 in adults with IMD (p < 0.01), but not in children (p = 0.45). Compared to other categories of IMD, complex molecule degradation disorders were significantly associated with more severe COVID-19 in children (p < 0.01); such a significant IMD category distinction was not found in adults., Discussion: This is the largest study on COVID-19 in IMD patients relying on real-word data and objective definitions, and not on merely expert opinions or physician surveys. COVID-19 severity and long COVID incidence in IMD are probably similar to the general population, and the risk of acute metabolic decompensation is not likely to be greater than that in other acute infections. Disease category (complex molecule degradation) in children, and comorbidities in adults may be associated with COVID-19 severity in IMD. Additionally, the first documented accounts of COVID-19 in 27 different IMD are recorded. The high occurrence of MIS-C may be coincidental, but warrants further study., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ochratoxin A (OTA) is a chemical produced by some fungal species, and although its toxic effects have been shown in many animal studies, there are limited studies in humans. We aimed to examine the relationship between OTA and hypertension. 50 newly diagnosed hypertensive patients and 33 healthy individuals aged between 12 and 14 were included in the study. Anthropometric measurements, blood pressure measurements, complete blood count, blood biochemical parameters, urine lead level and urine OTA level were measured. OTA was detected in the urine samples of 90.9% of the control group, 100% of the hypertensive group and 85.7% of the obese+hypertensive group. Median urinary OTA was 32.9 ng/g creatinine for hypertensive group, 32.2 ng/g creatinine for hypertensive+obese group, 18.8 ng/g creatinine for the control group. Multivariate logistic regression analysis revealed a positive association between last quartile of urinary OTA level and being hypertensive [AOR:5.93 (95%CI: 1.27-27.61)] in adolescents without obesity. Hypertensive cases could be evaluated for OTA exposure in further studies., Competing Interests: Competing interests Authors state no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: GM1 gangliosidosis is an autosomal recessive lysosomal storage disease caused by biallelic mutations in the GLB1 gene. Neurodegeneration, hypotonia, visceromegaly, macular cherry-red spots, skeletal dysplasia, and coarse and dysmorphic face are the major clinical features., Aims: To evaluate the demographic and clinical data of patients with GM1 gangliosidosis in a single center., Study Design: A retrospective clinical study., Methods: This study included patients followed at Hacettepe University İhsan Doğramacı Children’s Hospital Pediatric Metabolism Unit with the diagnosis of GM1 gangliosidosis between 1988 and 2021. Hospital records of the patients were reviewed for demographic, clinical, and laboratory findings., Results: Fourteen patients were included in the study and 10 (71.4%) were male. The age at onset of clinical symptoms was between 0 and 5 months, and the median time to diagnosis after the first symptom was 4.3 (0-13) months. Motor delay (54%) was the most common initial symptom. The median follow-up period was 14.8 (0.4-92.2) months. Twelve patients (85.7%) died, and all deaths occurred before the age of 24 months. The median survival was 21.3 (95% confidence interval, 15.5-24.9) months. Higher leukocyte beta-galactosidase activity correlated with later age at onset ( ρ = 0.575), later age at diagnosis ( ρ = 0.618), and longer diagnostic delay ( ρ = 0.702) ( ρ < 0.05)., Conclusion: Median survival in patients with GM1 gangliosidosis is less than 24 months. Beta-galactosidase enzyme activity may be associated with clinical onset and time of diagnosis in these patients.

We aimed to evaluate 14 urinary phthalate metabolites and 4 toxic metals in adolescents having thyroid colloid cyst (TCC) and compare with age and sex-matched others without TCC. Phthalate metabolites were analysed with UPLC-MS/MS and heavy metals with ICP-MS. TCC ratios in tertile subgroups of pollutants were compared with multiple logistic regression analysis after adjusting for age, sex, z-scores for body mass index and urinary creatinine values. Adolescents having the highest tertile of mono (2-ethylhexyl) phthalic acid and mercury had increased odds and those with the highest tertiles of monocarboxy-isononyl phthalate, mono (3-carboxypropyl) phthalate, monoisobutyl phthalate had lower odds for TCC than counterparts. The odds of TCC were lower for those in the second and the third tertiles. No differences in TCC ratios were detected with other pollutants. Given phthalate esters' and toxic metals' specific interactions on TCC, further studies were necessary to assess the influence of chemicals on TCC.

Background: Both exposure to toxic elements and hypertension (HT) are a global health problem. We planned to examine the associations between some toxic elements in urine, and blood pressure (BP) and its diurnal changes in adolescents., Methods: In this cross-sectional study, 48 adolescents who were newly diagnosed with HT and 38 adolescents with age-appropriate BP and normal physical examination were included. Anthropometric measurements, urinary toxic elements, carotid intima media thickness (cIMT), and office and 24-hour ambulatory BP measurements (ABPM) of participants were taken. Urinary elements levels were studied with ICP-MS. Elements were grouped in tertiles according to urinary levels. Logistic regression analyses were performed to show the interactions., Results: Urinary cadmium, mercury, lead, and arsenic were found to be at detectable level in 90.7%, 69.8%, 91.9% and 100% of the participants, respectively. Univariate analyses showed that elevated daytime systolic and/or diastolic BP was associated with urinary cadmium and mercury. No association between urinary toxic elements and nighttime BP was found. When height and body mass index z-scores adjusted for, age, gender, and all four urinary creatinine-corrected toxic elements analyzed, multiple logistic regression revealed that there was an association between mercury (high vs. low; AOR:3.85) and office HT, and mercury (high vs. low; AOR:6.18) and cadmium (middle vs. low; AOR: 13.38) were associated with "elevated 24-hour systolic BP and/or diastolic BP", and "elevated 24-hour mean arterial BP" in ABPM., Conclusion: There are complex relationships between toxic elements and BP parameters in adolescents, and more studies are needed to define the evolution of these relations., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Among the possible causes of hypertension in adolescence, electrolyte imbalances and environmental pollutants are drawing increasing attention. We aimed to examine the relationship between bisphenol A (BPA), phthalate metabolites, and serum electrolytes and blood pressure., Methods: Eighty-six participants aged 12-15 years were included in the study. Body mass index (BMI), office blood pressure and 24-h ambulatory blood pressure measurements (ABPM), and carotid intima-media thickness were determined. Blood samples were taken for hemogram, renal function tests, and serum electrolytes. Free- and total-BPA and phthalate metabolites were analyzed from urine samples., Results: Of the participants, 34 were evaluated as normal blood pressure profile, 33 as white-coat hypertension (WCHT), and 19 as ABPM-hypertension. Adolescents in ABPM- hypertension groups had higher BMI-standard deviation score (SDS), leucocyte, platelet count; but lower serum chloride, compared to the normal blood pressure profile group. The percentage of adolescents with detectable urinary mono-benzyl phthalate (MBzP) was higher in ABPM-hypertension (42.1%) and WCHT groups (33.3%), compared to the normal blood pressure profile group (5.9%, p = 0.004). Associations between MBzP and ABPM- hypertension and WCHT were remained after confounding factor adjustment. Adolescents with detectable MBzP levels had also higher "albumin-corrected calcium" and lower serum phosphate and "albumin-corrected calcium x phosphate product" compared to others. Adolescents with detectable urinary MBzP levels had higher blood pressure profiles in some 24-h (mean arterial pressure-SDS, systolic blood pressure-SDS), daytime (systolic blood pressure-SDS), and night-time (mean arterial pressure-SDS, systolic blood pressure-SDS, and diastolic blood pressure-SDS) measurements, compared to others. WCHT was found to be associated negatively with monomethyl phthalate and the sum of dibutyl phthalate metabolites and ABPM-HT with MCPP. There was no significant association between blood pressure profiles and free- and total-BPA status., Conclusion: MBzP was associated with adverse blood pressure profiles in adolescence. Additive follow-up studies are necessary for cause-effect relations., (© 2022. The Author(s).)

Background: Osteopontin (OPN) is a glycosylated phosphoprotein found in human tissues and body fluids. OPN in breast milk is thought to play a major role in growth and immune system development in early infancy. Here, we investigated maternal factors that may affect concentrations of OPN in breast milk, and the possible associated consequences for the health of neonates. Methods: General characteristics, health status, dietary patterns, and anthropometric measurements of 85 mothers and their babies were recorded antenatally and during postnatal follow-up. Results: The mean concentration of OPN in breast milk was 137.1 ± 56.8 mg/L. Maternal factors including smoking, BMI, birth route, pregnancy weight gain, and energy intake during lactation were associated with OPN levels ( p < 0.05). Significant correlations were determined between body weight, length, and head circumference, respectively, and OPN levels after one (r = 0.442, p = < 0.001; r = -0.284, p = < 0.001; r = -0.392, p = < 0.001) and three months (r = 0.501, p = < 0.001; r = -0.450, p = < 0.001; r = -0.498, p = < 0.001) of lactation. A negative relation between fever-related infant hospitalizations from 0-3 months and breast milk OPN levels (r = -0.599, p < 0.001) was identified. Conclusions: OPN concentrations in breast milk differ depending on maternal factors, and these differences can affect the growth and immune system functions of infants. OPN supplementation in infant formula feed may have benefits and should be further investigated.

Objectives: Lysosomal storage diseases (LSD) constitute an important group of metabolic diseases, consisting of approximately 60 disorders. In some types of lysosomal diseases, enzyme replacement therapy (ERT) is administered intravenously in weekly or biweekly doses. Unfortunately, scheduled ERT during COVID-19 was disrupted. We considered the possibility of adverse outcomes caused by the disruption in the treatment of patients with lysosomal storage disorders., Methods: During the COVID-19 pandemic, we conducted a questionnaire that was delivered via Internet to assess how this vulnerable patient group was affected by the pandemic in terms of their access to treatment and their disease-related symptoms., Results: The questionnaire was filled out by 75 patients. There were 35 patients whose treatment dose was missed because of COVID-19. The most common reason for skipping treatment was not wanting to go to the hospital for fear of contracting COVID-19. These 35 patients missed a median of four doses of ERT (range: 1-16 dosages). Twenty-one patients (60%) claimed that they were affected physically by not taking ERT (20 mucopolysaccaridoses, 1 Fabry disease), whereas 14 (40%) did not., Conclusions: Interruption of ERT during the COVID-19 pandemic may have significant consequences. It may be beneficial to switch to home treatment or reserve dedicated facilities. With proper planning and management, the treatment disruptions of this particular group can be avoided., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Phenylketonuria (PKU) is an inherited disorder of amino acid metabolism, the treatment of which often requires a special diet to prevent adverse neuropsychiatric outcomes. In the COVID-19 pandemic, which has had a substantial effect on the whole world since the beginning of 2020, PKU patients represent a vulnerable population because they may be dependent on special nutritional products, have limited access to routine care and display increased levels of anxiety., Methods: For this reason, an online questionnaire assessing the anxiety levels and various personal opinions and practices regarding the pandemic was sent to the PKU patients managed at our clinic, who were 12 years of age or older. Ninety-eight patients responded to the questionnaire. Median age of the participants was 19 years., Results: Most patients were compliant with the hygiene and social distancing recommendations regarding the spread of COVID-19. Of the patients, 61.2% felt more anxious since the pandemic. The most common concern was the possibility of not being able to obtain special nutritional products (58.2%). Anxiety level was significantly higher in females., Conclusions: These data suggest that food security is an important issue of concern in PKU patients. In line with the changing world after the pandemic, different strategies should be considered in the management of patients with inborn errors of metabolism, including PKU.

Background Obesity and obesity-related diseases are one of the common health problems worldwide and have also been proposed to be important predictors of blood pressure and cardiovascular disease risk. The aim of our study is to determine the utility of different anthropometric measurements (body mass index [BMI], skinfold thickness [SFT], waist circumference [WC], mid-upper arm circumference [MUAC], arm circumference-height ratio [AHtR], and waist circumference-height ratio [WHtR]) as markers of hypertension (HT) risk in adolescents. Methods In this cross-sectional study, 544 participants aged between 12 and 13 years were included. Anthropometric measurements and blood pressure of participants were measured. The association of different anthropometric measurements with blood pressure was evaluated. Results The frequency of both elevated blood pressure and HT was 30.2%. Biceps, triceps, and suprailiac SFT have an impact on HT in girls but only suprailiac SFT in boys. WC measurements above the 85th percentile were strongly correlated with HT conditions, and this relationship was stronger in boys than in girls (3.3 vs. 2.6 fold). MUAC, WHtR, and AHtR measurements also have strong correlation with HT in boys but only WHtR has a poor relation in girls. In boys and girls with obesity, there was a positive association between obesity and blood pressures. Conclusions Not only age-related BMI z scores but also a number of other anthropometric measurements, such as WC, SFT, MUAC, WHtR, and AHtR, could have an influence on high blood pressure. The influence changes with gender during adolescence.

Hyperspectral imagers enable the collection of high-resolution spectral images exploitable for the supervised classification of habitats and objects of interest (OOI). Although this is a well-established technology for the study of subaerial environments, Ecotone AS has developed an underwater hyperspectral imager (UHI) system to explore the properties of the seafloor. The aim of the project is to evaluate the potential of this instrument for mapping and monitoring benthic habitats in shallow and deep-water environments. For the first time, we tested this system at two sites in the Southern Adriatic Sea (Mediterranean Sea): the cold-water coral (CWC) habitat in the Bari Canyon and the Coralligenous habitat off Brindisi. We created a spectral library for each site, considering the different substrates and the main OOI reaching, where possible, the lower taxonomic rank. We applied the spectral angle mapper (SAM) supervised classification to map the areal extent of the Coralligenous and to recognize the major CWC habitat-formers. Despite some technical problems, the first results demonstrate the suitability of the UHI camera for habitat mapping and seabed monitoring, through the achievement of quantifiable and repeatable classifications.

This work is devoted to discuss some spectral properties and the scattering function of the impulsive operator generated by the Sturm-Liouville equation. We present a different method to investigate the spectral singularities and eigenvalues of the mentioned operator. We also obtain the finiteness of eigenvalues and spectral singularities with finite multiplicities under some certain conditions. Finally, we illustrate our results by a detailed example., Competing Interests: The authors declare that they have no competing interests.