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Background: Phenylketonuria (PKU) is an inherited error of metabolism, screened at 48–72 h of life since 1975 in Hungary. The patients have to keep a strict lifelong protein-restricted diet, resulting in PKU and its treatment can lead to social and financial burdens. The current study aimed to evaluate the health-related quality of life (HRQoL) of children living with PKU. Patients and methods: A single-centre, cross-sectional, observational study was conducted at the Center of Newborn Screening and Inherited Metabolic Disorders of Budapest, Hungary, using the PKU-quality of life (PKU-QoL) questionnaire. Responses of 59 parents and 11 teenagers were collected. Numerous aspects regarding HRQoL were analysed according to clinical compliance and severity. The patients were classified into groups with good or suboptimal adherence based on regular phenylalanine (Phe) values. The online officially translated versions of the adolescent or parental PKU-QoL questionnaire were used and analysed anonymously. Differences in HRQoL were compared - PKU vs. Hyperphenylalaninaemia (HPA) and good vs. suboptimal adherence. Results: Twenty-five of 32 examined parameters had no or little impact on HRQoL. The most frequently reported symptom was irritability. Food enjoyment was the most impacted domain, with a major severity score in the adolescent group (median 62,5, IQR: 25–75). The emotional impact was scored at moderate severity by both the adolescents and parents. Classical PKU patients with good metabolic control were more frequently tired than HPA patients (0,0027). The group with poor metabolic adherence showed more frequent tiredness (p = 0,03), slow thinking (p = 0,018) and anxiety (p = 0,015). Conclusion: Overall, our patients showed an excellent HRQoL; most domains (29/36) were reported as little/no impacted. Worse QoL was found in patients with suboptimal metabolic control. Particular attention should be paid to the emotional health of PKU patients.

In neonatal screening, amino acids have a significant diagnostic role. Determination of their values may identify abnormal conditions. Early diagnosis and continuous monitoring of amino acid disorders results in a better disease outcome. An easy and simple LC-MS/MS method was developed for the quantitation of underivatized amino acids. Amino acids were separated using a normal-phase HPLC column having a totally porous silica stationary phase and using classical reversed-phase eluents. Mass spectrometry in multiple reaction monitoring mode was used for the analysis, providing high selectivity and sensitivity. A standard addition calibration model was applied for quantitation using only one isotope-labeled internal standard for all amino acids. Five calibration points were used for quantitation, and the method was successfully validated. The slopes of the calibration curves of the individual amino acids in parallel measurements were found to be similar. Since the measured slopes were reproducible, one serum sample could represent every series of serum samples of a given day. The method was tested on human serum samples and adequate results were obtained. This new method can be easily applied in clinical laboratories.

The aim of our study was to describe the characteristics of patients with classical galactosemia in Croatia, with the description of patients with galactokinase deficiency and a patient who was a double heterozygote for mutations of the galactose-1-phosphate uridyl transferase (GALT), and galactose-4’-epimerase (GALE) genes. The study included 24 patients who were diagnosed with classic galactosemia from 1977 to 2020. Diagnosis was based on clinical presentation and galactose concentrations in blood and urine, and confirmed by measuring galactose-1-phosphate-uridyl-transferase activity and/or GALT gene analysis. Acute manifestations of the disease developed in 87% of patients in the newborn period, and one patient died. The median age at the onset of first symptoms was four days and for onset of therapy 11.5 days. At least one long-term complication occured in 78.3% of patients, including developmental disorders (68.2%), behavioral disorders (31.8%), speech disorders (55.6%), impaired intellectual abilities (46.2%), other neurological complications (40.9%), cataract (18.2%), and decreased bone mineral density (27.8%). Ovarian insufficiency occured in 66.7% of female patients older than 10 years. When comparing siblings, although a galactose-free diet was started earlier in the second-born children with classical galactosemia, the incidence of long-term outcomes did not appear to be related to birth order. In conclusion, this study shows that the vast majority of patients develop symptoms in the neonatal period, as well as long-term complications, despite strict adherence to a galactose-free diet. Many factors that affect the pathogenesis and clinical course of the disease are still unknown, which is why further research into classical galactosemia is needed.

The aim of this study is to evaluate the strategy of the cystic fibrosis newborn screening (CFNBS) programme in Hungary based on the results of the first year of screening. A combined immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) CFNBS protocol (IRT/IRT×PAP/IRT) was applied with an IRT-dependent safety net (SN). Out of 88,400 newborns, 256 were tested screen-positive. Fourteen cystic fibrosis (CF) and two cystic fibrosis-positive inconclusive diagnosis (CFSPID) cases were confirmed from the screen-positive cases, and two false-negative cases were diagnosed later. Based on the obtained results, a sensitivity of 88% and a positive predictive value (PPV) of 5.9% were calculated. Following the recognition of false-negative cases, the calculation method of the age-dependent cut-off was changed. In purely biochemical CFNBS protocols, a small protocol change, even after a short period, can have a significant positive impact on the performance. CFNBS should be monitored continuously in order to fine-tune the screening strategy and define the best local practices.

Background: Patients with phenylketonuria (PKU) must maintain a lifelong natural protein-restricted diet to prevent neuro-cognitive damage. Early diagnosis is established with newborn screening, with diet subsequently controlled by regular phenylalanine (Phe) monitoring. During the COVID-19 pandemic, significant lockdown measures were introduced that may have influenced the above. Aim of our study: To establish whether the diagnosis was delayed in neonates during the pandemic. In addition, metabolic control was further assessed during the COVID-19 pandemic era (CE) compared to the same period a year prior (non-COVID-19 era, NCE). The lockdown periods (LD) were also compared with unrestricted periods (URP). Patients, methods: Six neonates born during the CE and eight neonates born during NCE were included in the newborn screening analysis. Seventy-two classical PKU patients aged 2–18 years and categorized as children (2–12 years; 51 patients) and adolescents (>13 years; 21 patients) were included in the metabolic control analysis. The frequency of dried blood spot (DBS) sampling and Phe levels were assessed according to the different periods. Results: There was no diagnostic or therapeutic delay in reaching the recommended Phe range in neonates born during CE compared to those born in NCE (median [interquartile range, IQR]: 23.5 [22.5–24] vs. 22 [18.0–27] days, p = NS). The cumulative DBS sampling frequency in children increased by 9.9% in the CE while no change was noted in the adolescent group. The median Phe level increased significantly in both age groups in the CE, but remained within the recommended target range. During CE, changes in Phe levels differed in the two age groups: children had the highest median Phe in the second lockdown period (LD2), while the adolescents had an increased Phe in URP.There were significant negative correlations between DBS sampling frequencies and Phe levels in both age groups in NCE (children: r − 0.43, p = 0.002; adolescents r = −0.37, p = 0.012), and in adolescents in CE (r = −0.62, p = 0.006). Conclusion: The pandemic did not impact newborn metabolic screening. The increased frequency of DBS sampling in CE and good target Phe levels suggest a better compliance in a very sensitive period. Since many factors may impact metabolic control in the different age groups, further studies are needed to analyse their respective role.