Phenylketonuria (PKU), an autosomal-recessive inborn error of phenylalanine (Phe) metabolism is the most prevalent disorder of amino acid metabolism. Currently, clinical follow-up relies on frequent monitoring of Phe levels in blood. We hypothesize that the urine level of phenylacetylglutamine (PAG), a phenyl-group marker, could be used as a non-invasive biomarker. In this cross-sectional study, a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS) method was used for urinary PAG quantification in 35 participants with hyperphenylalaninemia (HPA) and 33 age- and sex-matched healthy controls. We have found that (a) PKU patients present higher urine PAG levels than healthy control subjects, and that (b) there is a significant correlation between urine PAG and circulating Phe levels in patients with HPA. In addition, we show a significant strong correlation between Phe levels from venous blood samples and from capillary finger-prick dried blood spot (DBS) samples collected at the same time in patients with HPA. Further research in order to assess the potential role of urine PAG as a non-invasive biomarker in PKU is warranted.

Hereditary Fructose Intolerance (HFI) is an autosomal recessive inborn error of metabolism characterised by the deficiency of the hepatic enzyme aldolase B. Its treatment consists in adopting a fructose-, sucrose-, and sorbitol (FSS)-restrictive diet for life. Untreated HFI patients present an abnormal transferrin (Tf) glycosylation pattern due to the inhibition of mannose-6-phosphate isomerase by fructose-1-phosphate. Hence, elevated serum carbohydrate-deficient Tf (CDT) may allow the prompt detection of HFI. The CDT values improve when an FSS-restrictive diet is followed; however, previous data on CDT and fructose intake correlation are inconsistent. Therefore, we examined the complete serum sialoTf profile and correlated it with FSS dietary intake and with hepatic parameters in a cohort of paediatric and adult fructosemic patients. To do so, the profiles of serum sialoTf from genetically diagnosed HFI patients on an FSS-restricted diet (n = 37) and their age-, sex- and body mass index-paired controls (n = 32) were analysed by capillary zone electrophoresis. We found that in HFI patients, asialoTf correlated with dietary intake of sucrose (R = 0.575, p < 0.001) and FSS (R = 0.475, p = 0.008), and that pentasialoTf+hexasialoTf negatively correlated with dietary intake of fructose (R = −0.386, p = 0.024) and FSS (R = −0.400, p = 0.019). In addition, the tetrasialoTf/disialoTf ratio truthfully differentiated treated HFI patients from healthy controls, with an area under the ROC curve (AUROC) of 0.97, 92% sensitivity, 94% specificity and 93% accuracy.

Background: Leigh syndrome (LS) is a serious genetic disease that can be caused by mutations in dozens of different genes. Methods: Clinical study of a deafness pedigree in which some members developed LS. Cellular, biochemical and molecular genetic analyses of patients’ tissues and cybrid cell lines were performed. Results: mitochondrial DNA (mtDNA) m.1555A>G/MT-RNR1 and m.9541T>C/MT-CO3 mutations were found. The first one is a well-known pathologic mutation. However, the second one does not appear to contribute to the high hearing loss penetrance and LS phenotype observed in this family. Conclusion: The m.1555A>G pathological mutation, accompanied with an unknown nuclear DNA (nDNA) factor, could be the cause of the phenotypic manifestations in this pedigree.

Background/Objectives: Hereditary fructose intolerance (HFI) is an inherited metabolic disorder caused by a deficiency of the enzyme fructose-1,6-bisphosphate aldolase. Treatment consists of a lifelong diet restricted in fructose, sucrose, and sorbitol (FSS). The aim of this study was to determine dietary intake of FSS and to analyze the consumption patterns of vegetables, fruit, legumes, pulses, and dried fruit in a nationwide cohort of HFI patients. Methods: Overall, 36 HFI patients and 28 age-, sex- and BMI-matched healthy control subjects participated in this study. A self-administered three-day dietary record and an adapted quantitative food frequency questionnaire (FFQ) including frequency and portion sizes were collected. FSS intake was calculated using the DIAL Nutritional Calculation Program (ALCE INGENIERÍA). Total fructose intake was calculated as the sum of free fructose, 50% of sucrose, and sorbitol. Results: Protein intake was significantly higher in HFI patients compared to the controls (92.43 g/day [65.1–165.03] vs. 70.39 g/day [35.21–133.83]; p = 0.001). In most patients, total fructose intake was within the recommended limits (9.79 mg/kg bw/day [0.29–59.09]), with no significant differences between children and adults (p = 0.325). Although the established dietary recommendations did not always match the actual intake observed in a real-life setting, in general, foods with higher fructose content were consumed less frequently and in smaller quantities. Conclusions: Further research on the fructose content of various foods, particularly fruits and vegetables, and updated dietary recommendations for HFI patients are warranted to provide the best tools for the nutritional management of the disease.