JIMD reports最新文献

{"title":"Calculation of continuous reference intervals for biological parameters exhibiting strong age-dependent level changes: Its application to glycosaminoglycans and sialic acid in urine","authors":"Carlos Emilio Rodríguez,&nbsp;Mette Diswall,&nbsp;Anders Olsson,&nbsp;Torleif Jonsson,&nbsp;Eva Johansson,&nbsp;Maria Blomqvist","doi":"10.1002/jmd2.12448","DOIUrl":"10.1002/jmd2.12448","url":null,"abstract":"<p>Glycosaminoglycan (GAG) and sialic acid (total and free) assays are used as first-line screening tests for the diagnosis of mucopolysaccharidoses and glycoproteinoses, respectively. There is a pronounced age-dependent variation in the urinary concentrations of these metabolites in the normal population, and the stratification of the reference values into discrete age ranges may lead to an undesirably high number of false-positive or false-negative results. The aim of this study was to design a method for calculating continuous reference intervals as a function of age and its application to the analysis of GAGs and sialic acid (total, free, and conjugated) in urine. In the postpubertal period, concentrations of urinary GAGs and sialic acid have reached a plateau, so a traditional calculation of the reference range in this specific age group was considered appropriate. In the prepubertal period, a nonlinear regression performed with the Excel add-in Solver was used to fit the logarithmized concentrations of the controls to a curve that represents the mean values as a function of age. A uniform distribution of the residuals was obtained, which allowed the calculation of the reference intervals by adding the values of their 2.5 and 97.5 percentiles to the independent variable of the regression curve to calculate the upper and lower reference curves. The main advantages of the developed method are (1) a reduction in the number of control samples needed to obtain adequate reference intervals and (2) an improvement in the reliability of diagnostic screening by reducing the uncertainty generated by the gaps in the traditional age-stratified method.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"442-449"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical experience on switching trientine tetrahydrochloride to trientine dihydrochloride in Wilson disease patients","authors":"Isabelle Mohr,&nbsp;Timo Schmitt,&nbsp;Christophe Weber,&nbsp;Nicolas Schall,&nbsp;Viola Yuriko Leidner,&nbsp;Andrea Langel,&nbsp;Jessica Langel,&nbsp;Aurélia Poujois,&nbsp;Karl Heinz Weiss,&nbsp;Uta Merle","doi":"10.1002/jmd2.12451","DOIUrl":"10.1002/jmd2.12451","url":null,"abstract":"<p>This study evaluates the effectiveness and safety of trientine dihydrochloride (TETA 2-HCl) in patients with Wilson disease (WD) following a switch from trientine tetrahydrochloride (TETA 4-HCl). A total of 30 WD patients with stable copper metabolism were identified for treatment with TETA 2-HCl (Cufence™) after prior use of TETA 4-HCl (Cuprior™). Biochemical markers including urinary copper, non-ceruloplasmin bound copper (NCC) and liver function were analyzed at baseline and followed up over 12 months. Safety was assessed based on reported adverse events (AEs). Urinary copper levels and NCC remained stable across all follow-ups, indicating adequate copper metabolism control. Reported AEs during TETA 2-HCl treatment were mostly gastrointestinal discomfort (<i>n</i> = 6). In two patients, progressive elevation of transaminases occurred (despite stable copper metabolism). AEs led to discontinuation of treatment in five cases. Median baseline dose per day was 10.2 mg TETA 4-HCl/kg bodyweight, whereas median baseline dose after therapeutic switch to TETA 2-HCl was 12.8 mg/kg bodyweight. Median daily dose at 12 months did not differ significantly from TETA 2-HCl dose at switching timepoint, with stable biochemical markers and markers of copper metabolism in most (25/30) of the patients. Transitioning from TETA 4-HCl to TETA 2-HCl maintained stable copper parameters and liver function in most of analyzed patients. TETA 2-HCl treatment was generally well tolerated, suggesting that switching medications is safe and effective. In our real-life cohort, adjustment factor of ~1.25× for the switch of TETA 4-HCl to TETA 2-HCl resulted in adequate copper metabolism control.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"406-416"},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo glycerol metabolism in patients with glycerol kinase deficiency","authors":"Ankit Shah,&nbsp;Huiting Xu,&nbsp;Hyok Joon Kwon,&nbsp;Fredric E. Wondisford","doi":"10.1002/jmd2.12452","DOIUrl":"10.1002/jmd2.12452","url":null,"abstract":"<p>Glycerol kinase deficiency (GKD) is an X-linked recessive disorder due to <i>glycerol kinase</i> (<i>GK</i>) gene mutations resulting in hyperglycerolermia, hyperglyceroluria, and “pseudohypertriglyceridemia.” In vivo glycerol metabolism has not been assessed in GKD. A 62-year-old man with suspected GKD and his extended family underwent whole exome sequencing and fasting blood work with two modes of lipid measurements: (1) standard lipase-based methodology and (2) nuclear magnetic resonance (NMR). Two overnight fasted men with GKD and a heterozygote female carrier then underwent ¹³C₃-glycerol infusion. Affected family members had a novel two-nucleotide deletion in exon 5 of the <i>GK</i> gene (c.373_374del). Compared to their family members (<i>n</i> = 14), men with GKD (<i>n</i> = 5) had significantly lower total cholesterol levels (3.72 ± 0.70 vs. 4.77 ± 0.85 mmol/L, <i>p</i> = 0.024). Compared to NMR, lipase-based assays overreported triglycerides (5.28 ± 1.38 vs. 0.81 ± 0.32, mmol/L, <i>p</i> &lt; 0.001) and underreported low-density lipoprotein cholesterol values (0.93 ± 0.23 vs. 2.18 ± 0.42 mmol/L, <i>p</i> = 0.001) in GKD. Men with GKD could not convert glycerol into glucose or triglycerides, which was preserved in the heterozygote carrier. Glycolytic metabolism of glycerol to lactate persisted in GKD, but it was reduced by a magnitude and, possibly, due to homologous glycerol kinases encoded by other genes. In summary, we report a novel <i>GK</i> pathogenic variant; affected men cannot convert circulating glycerol to glucose or triglycerides and have lower cholesterol levels. These results offer a human model for potentially targeting glycerol kinase to treat conditions associated with hyperglycemia and hyperlipidemia and warrant further investigation.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"392-400"},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymptomatic pediatric presentation of S-adenosylhomocysteine hydrolase deficiency","authors":"Patrícia Lipari Pinto,&nbsp;Marjorie Dixon,&nbsp;Sniya Sudhakar,&nbsp;Ivo Baric,&nbsp;Julien Baruteau","doi":"10.1002/jmd2.12449","DOIUrl":"10.1002/jmd2.12449","url":null,"abstract":"<p>S-adenosylhomocysteine hydrolase deficiency is an autosomal recessive inborn error of metabolism affecting methylation by disrupting the methionine cycle. Its clinical spectrum spans from severe perinatal encephalomyopathy and liver failure to asymptomatic course in patients with isolated hypermethioninemia. We present two new cases of S-adenosylhomocysteine hydrolase deficiency from Pakistani origin clinically asymptomatic at presentation. Both siblings showed mild chronic liver failure and elevation of creatine kinase. The older patient presented at 6 years of age with isolated verbal processing difficulty and mild diffuse leukodystrophy, reversible 12 months after introduction of methionine dietary restriction. The patient showed subtle atrophy in the muscle MRI at the age of 7 years. S-adenosylhomocysteine hydrolase deficiency was confirmed with homozygous missense variant c.146G&gt;A (p.Arg49His) in the <i>AHCY</i> gene, a genotype previously reported in Pakistani patients with mild presentation. Dietary methionine restriction decreased plasma methionine but not plasma S-adenosylhomocysteine and S-adenosylmethionine. This work expands the mild spectrum of S-adenosylhomocysteine hydrolase deficiency with no noticeable clinical symptoms in children, highlighting a specific hotspot variant from South Asia. This mild form of the disease is likely underdiagnosed and raises the question of therapeutic management to prevent long-term complications documented in the literature, such as hepatocellular carcinoma and myopathy in early adulthood.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"371-381"},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective analysis of arginase 1 deficiency progression in adults over 5 years at a single metabolic centre","authors":"Reena Sharma,&nbsp;John Bassett,&nbsp;Karolina M. Stepien,&nbsp;Andrew Oldham,&nbsp;Ana Jovanovic,&nbsp;Alison Woodall,&nbsp;Diane Green","doi":"10.1002/jmd2.12450","DOIUrl":"10.1002/jmd2.12450","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The clinical presentation of ARG1-D is characterised by elevated arginine levels leading to neurological and mobility impairments. Information about long-term outcomes in adults is lacking, which prompted us to undertake a retrospective observational study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We extracted ARG1-D patient data spanning a 5-year period from electronic health records. Ethical approval was not required for the study. Informed consent was obtained.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified nine ARG1-D patients from consanguineous backgrounds. Age of symptom onset ranged from infancy to age 7 years, age of diagnosis from infancy to 20 years. Patients had paraparesis or altered gait of varying degree and had experienced early ARG1-D onset. Over 5 years, mobility declined in six (6/9, 67%) patients. Three patients (3/9, 33%) were fully dependent and hoisted. Two (2/9, 22%) reached adulthood before experiencing hyperammonaemia, another one (1/9, 11%) first experienced hyperammonaemia at age 15 years. One patient (1/9, 11%) started on ammonia scavenger therapy in adulthood, one (1/9, 11%) required a second scavenger to be added to their treatment regimen. Two patients (2/9, 22%) had gastrostomy tubes inserted for nutrition and supplements at age 9 years and 15 years. Six patients (6/9, 67%) had raised levels of ALT; of these, four (4/9, 44%) also had elevated AFP. Heterogeneity of ARG1-D symptoms was evident, suggesting complex genetic and environmental interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ARG1-D presents significant lifelong challenges with deteriorating mobility and more frequent metabolic crises. Current management strategies are insufficient for preventing progression, highlighting the need for innovative treatments like enzyme replacement and gene therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"382-391"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olfactory and gustatory perception in Brazilian PKU patients: A cross-sectional study","authors":"Tássia Tonon,&nbsp;Chenia Martinez,&nbsp;Tatiele Nalin,&nbsp;Soraia Poloni,&nbsp;Otávio Bejzman Piltcher,&nbsp;François Maillot,&nbsp;Bianca Fasolo Franceschetto,&nbsp;Ida Vanessa D. Schwartz","doi":"10.1002/jmd2.12445","DOIUrl":"10.1002/jmd2.12445","url":null,"abstract":"<p>Patients with phenylketonuria (PKU) have a highly restrictive diet, which involves restriction of phenylalanine (Phe) intake and daily use of Phe-free metabolic formula. However, little is known about the potential impact of this diet on chemical senses. The present study aimed to evaluate the olfactory and gustatory perceptions of patients with PKU. A cross-sectional controlled study which included patients with PKU on dietary treatment and healthy controls was performed. Olfactory perception was assessed using the 12-item <i>Sniffin’ Sticks</i> test, and taste perception using the <i>Taste Strips</i> test. Twenty-five patients (mean age 19.3 ± 4.7 years; 13 females) and 25 controls (mean age 19.9 ± 4.9 years, <i>p</i> = 0.676; 13 females) were included. The mean age at treatment onset was 52.8 ± 29.7 days. The mean scores for olfactory and gustatory perceptions, and for bitter and salty flavors, were lower in patients than in controls (<i>p</i> = 0.039, <i>p</i> = 0.004, <i>p</i> = 0.008, and <i>p</i> = 0.020, respectively). Among patients, Phe levels at diagnosis correlated negatively with bitter taste (<i>r</i> = −0.493, <i>p</i> = 0.006). The lower olfaction and gustation scores found in patients may be related to understimulation caused by the highly restrictive PKU diet and the deprivation of flavors from breast milk.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"426-432"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced differentiation between 3-hydroxyglutaric and 2-hydroxyglutaric acids facilitates diagnostic testing for glutaric aciduria type 1","authors":"Denis Cyr,&nbsp;Michel Boutin,&nbsp;Bruno Maranda,&nbsp;Paula J. Waters","doi":"10.1002/jmd2.12447","DOIUrl":"10.1002/jmd2.12447","url":null,"abstract":"<p>Glutaric aciduria type 1 (GA1) is an inherited neurometabolic disorder, in which deficiency of glutaryl-CoA dehydrogenase leads to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3-HG). Some low excretors may exhibit only slight elevation of urinary 3-HG, with normal urinary GA, yet are at significant risk of severe clinical disease. Accurate quantitation of urinary 3-HG is crucial in diagnostic workup for GA1, but in this context, current gas chromatography–mass spectrometry (GC–MS) methods have inherent analytical challenges. Co-elution and spectral similarities of the 3-HG and 2-HG structural isomers can cause difficulties in quantitation of slightly elevated 3-HG. Our laboratory recently acquired a gas chromatography system coupled to a triple quadrupole mass spectrometer (GC–MS/MS), and we took advantage of its increased sensitivity and specificity to improve our existing GC–MS method. A stable isotope dilution process is used, with sample treatment consisting of a double liquid–liquid extraction followed by a trimethylsilyl derivatization. The transitions <i>m</i>/<i>z</i> 349 → 333 for 3-HG and <i>m</i>/<i>z</i> 349 → 321 for 2-HG were selected to differentiate these two isobaric molecules based on their characteristic fragments, thus minimizing interferences despite co-elution. Method validation demonstrated satisfactory precision and accuracy. Using GC–MS/MS instead of GC–MS allowed us to decrease the required specimen volume, number of sample processing steps, chromatographic run time, and instrument maintenance. This enhanced assay facilitates clinical laboratory testing for GA1, both in confirmatory protocols following positive newborn screening and in diagnostic investigation of patients with suggestive signs or symptoms.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"433-441"},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydrolipoamide dehydrogenase deficiency in five siblings with variable phenotypes, including fulminant fatal liver failure despite good engraftment of transplanted liver","authors":"Mihaela Mihaljević,&nbsp;Danijela Petković Ramadža,&nbsp;Tamara Žigman,&nbsp;Ivana Rako,&nbsp;Slobodan Galić,&nbsp;Toni Matić,&nbsp;Filip Rubić,&nbsp;Ivana Čulo Čagalj,&nbsp;Davor Mayer,&nbsp;Ante Gojević,&nbsp;Stanko Ćavar,&nbsp;Marijana Ćorić,&nbsp;Melanie T. Achleitner,&nbsp;Johannes A. Mayr,&nbsp;Ksenija Fumić,&nbsp;Jurica Vuković,&nbsp;Ivo Barić","doi":"10.1002/jmd2.12444","DOIUrl":"https://doi.org/10.1002/jmd2.12444","url":null,"abstract":"<p>Dihydrolipoamide dehydrogenase (DLD) deficiency can, in one of its forms, be a rare cause of acute liver failure. Clinical presentation is nonspecific. Biochemical findings can reflect metabolic block, but vary depending on patient and his condition. Consensus treatment guidelines do not exist. We present a family with five members suffering from DLD deficiency. Patient 1 presented with emesis, mental deterioration, and fulminant hepatic failure, which required high-urgency liver transplantation. His younger brother, patient 2, experienced unexplained hypoglycemia and metabolic acidosis on the second day after cardiac surgery. Three affected younger siblings were asymptomatic. In patients with acute liver failure of unknown etiology urgent metabolic work-up should be done, and whole exome sequencing considered. Liver transplantation remains life-saving treatment option, but its outcome may be dependent on etiology-specific supportive treatment.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 5","pages":"323-329"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the genetic and clinical spectrum of SLC25A42-associated disorders and testing of pantothenic acid to improve CoA level in vitro","authors":"Katharina Heckmann,&nbsp;Arcangela Iuso,&nbsp;Janine Reunert,&nbsp;Marianne Grüneberg,&nbsp;Anja Seelhöfer,&nbsp;Stephan Rust,&nbsp;Giuseppe Fiermonte,&nbsp;Eleonora Paradies,&nbsp;Carmela Piazzolla,&nbsp;Manoj Mannil,&nbsp;Thorsten Marquardt","doi":"10.1002/jmd2.12441","DOIUrl":"10.1002/jmd2.12441","url":null,"abstract":"<p><i>SLC25A42</i> encodes the mitochondrial coenzyme A (CoA) transporter localized at the inner mitochondrial membrane. SLC25A42 deficiency leads to a congenital disease with a heterogeneous clinical presentation, including myopathy, developmental delay, lactic acidosis, and encephalopathy. Twenty-one patients have been described so far. In the current study, we report on the identification of new biallelic variants in <i>SLC25A42</i> in three siblings. Patients presented with symmetrical T2 hyperintensity of the putamen with minor volume depression at the brain MRI, elevated lactate, reduced oxygen consumption rates in muscle and fibroblasts, and reduced CoA levels in fibroblasts. Administration of pantothenic acid led to clinical stabilization and increased CoA levels in fibroblasts, thus confirming a role for SLC25A42 in energy metabolism and CoA homeostasis.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"417-425"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do early-treated adults with phenylketonuria sense high phenylalanine levels?","authors":"Laura Hauri,&nbsp;Raphaela Muri,&nbsp;Regula Everts,&nbsp;Roman Trepp","doi":"10.1002/jmd2.12446","DOIUrl":"https://doi.org/10.1002/jmd2.12446","url":null,"abstract":"<p>This study aimed to analyze whether early-treated adults with phenylketonuria (PKU) can subjectively sense high phenylalanine (Phe) concentrations and whether a possible impact of Phe on objective measures of cognitive performance and mood reflects patients' self-perception. Data from the PICO study, a randomized, placebo-controlled, double-blind, crossover trial, were analyzed. Twenty-eight adults with PKU received either Phe capsules or placebo in two 4-week intervention periods in a randomized order, with a 4-week washout in between. The median Phe level increased from 852 μmol/L (interquartile range: 345) to 1455 μmol/L (interquartile range: 369). Neuropsychological assessments were performed at four study visits. At the end of the last study visit, patients were asked whether they could discern the Phe intervention period. Seven of 28 (25%) patients stated that they could not discern between the Phe and the placebo period. Twenty-one of 28 (75%) patients subjectively thought to sense high Phe levels. Of the 21 patients, 12 (57%) correctly identified the Phe period, whereas 9 (43%) received placebo at the time when they thought they would receive the high Phe load. Binomial tests showed that the probability of 12 out of 21 is <i>p</i> = 0.140, and 12 out of 28 is <i>p</i> = 0.113. The “Right-Guess” group showed significantly higher Phe changes than the “Wrong-Guess” group. Cognitive performance and standardized mood assessment did not significantly differ, and both groups reported similar subjective negative impact on cognition and mood. In conclusion, adults with early-treated PKU cannot effectively identify high Phe levels, although some individuals may be able to perceive more pronounced increases in Phe levels.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 5","pages":"354-358"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}