JIMD reports最新文献

{"title":"A Deep Clinical and Biochemical Characterization of a Patient With Combined Malonic and Methylmalonic Aciduria (CMAMMA)","authors":"Vincenza Gragnaniello,&nbsp;Alfonso Galderisi,&nbsp;Sara Tucci,&nbsp;Mara Doimo,&nbsp;Marianna Caterino,&nbsp;Christian Loro,&nbsp;Chiara Cazzorla,&nbsp;Margherita Ruoppolo,&nbsp;Leonardo Salviati,&nbsp;Alberto B. Burlina","doi":"10.1002/jmd2.70045","DOIUrl":"10.1002/jmd2.70045","url":null,"abstract":"<p>Combined malonic and methylmalonic aciduria (CMAMMA) is an inborn error of metabolism caused by a deficiency in mitochondrial malonyl-CoA synthetase, the enzyme responsible for activating malonic acid (MA) to malonyl-CoA, a precursor of lipoic acid. The clinical phenotype is highly heterogeneous, ranging from asymptomatic cases to severe neurological impairment. We describe a patient affected by CMAMMA. The patient presented in the neonatal period with hyperinsulinemic hypoglycemia. Urinary organic acid analysis revealed elevated levels of both malonic and methylmalonic acids. The diagnosis of CMAMMA was confirmed through molecular testing of the <i>ACSF3</i> gene. Levels of both lipoylated pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (αKGDH) were decreased. Given the role of lipoic acid in regulating insulin secretion, the involvement of impaired mitochondrial lipoic acid biosynthesis in the clinical presentation of hyperinsulinemic hypoglycemia cannot be excluded. We describe a case of CMAMMA associated with hyperinsulinemic hypoglycemia. While a definitive association between CMAMMA and hyperinsulinism cannot be established based on a single case, the observed reduction in lipoic acid levels may suggest a mechanistic connection between the two disorders. We suggest considering urinary organic acid testing in patients with hyperinsulinism, especially when the cause is unknown.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199477","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":"Splenic Artery Aneurysm in Gaucher Disease: A Hybrid Study Combining Case Report, Scoping Review, and Clinical Survey","authors":"Paolo Manzi,&nbsp;Anita Vergatti,&nbsp;Veronica Abate,&nbsp;Nadia Altavilla,&nbsp;Michelina Sibilio,&nbsp;Pietro Venetucci,&nbsp;Paolo Tirelli,&nbsp;Domenico Rendina,&nbsp;Antonio Barbato","doi":"10.1002/jmd2.70044","DOIUrl":"https://doi.org/10.1002/jmd2.70044","url":null,"abstract":"<p>Gaucher disease (GD) is a rare lysosomal storage disorder caused by pathogenic variants in the <i>GBA</i> gene. Splenic artery aneurysm (SAA) is an uncommon and underrecognized complication of GD, particularly in the absence of traditional risk factors. SAA carries a high risk of rupture and significant mortality. This hybrid study investigates the clinical features and impact of SAA in GD through a three-part approach: a case report, a scoping review with individual patient data (IPD) analysis, and a clinical survey conducted across two GD centers in Naples, Italy. We report the case of a 46-year-old woman with GD type 1, in whom a 37 × 32 mm calcified SAA was incidentally found. Despite the high risk of rupture, the patient opted for regular radiological monitoring. Over a 16-year follow-up period, the aneurysm remained stable. In the literature, we identified 11 GD subjects (four [36.4%] males and seven [63.6%] females) with SAA, including our case report. Most had not received enzyme replacement therapy (ERT) or were non-compliant before the SAA diagnosis. Only two patients reported abdominal pain, and one died due to intraoperative hemorrhage. In our clinical survey, the prevalence of SAA in GD patients was 2.1%, twice that reported in individuals without GD. Although SAA is a rare and often underdiagnosed complication in GD, its potential lethality warrants heightened clinical awareness. We recommend incorporating magnetic resonance imaging for routine evaluation of the spleen and splenic artery in GD patients. This strategy, in conjunction with timely ERT, may be life-saving.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135561","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":"Metabolic Control and Frequency of Clinical Monitoring Among Canadian Children With Phenylalanine Hydroxylase Deficiency: A Retrospective Cohort Study","authors":"Nataliya Yuskiv,&nbsp;Ammar Saad,&nbsp;Beth K. Potter,&nbsp;Sylvia Stockler-Ipsiroglu,&nbsp;John J. Mitchell,&nbsp;Steven Hawken,&nbsp;Kylie Tingley,&nbsp;Michael Pugliese,&nbsp;Monica Lamoureux,&nbsp;Andrea J. Chow,&nbsp;Jonathan B. Kronick,&nbsp;Kumanan Wilson,&nbsp;Annette Feigenbaum,&nbsp;Sharan Goobie,&nbsp;Michal Inbar-Feigenberg,&nbsp;Julian Little,&nbsp;Saadet Mercimek-Andrews,&nbsp;Amy Pender,&nbsp;Chitra Prasad,&nbsp;Andreas Schulze,&nbsp;Yannis Trakadis,&nbsp;Gloria Ho,&nbsp;Hilary Vallance,&nbsp;Valerie Austin,&nbsp;Anthony Vandersteen,&nbsp;Andrea C. Yu,&nbsp;Cheryl Rockman-Greenberg,&nbsp;Aizeddin A. Mhanni,&nbsp;Pranesh Chakraborty","doi":"10.1002/jmd2.70042","DOIUrl":"https://doi.org/10.1002/jmd2.70042","url":null,"abstract":"<p>Achieving and maintaining metabolic control is critical for children with phenylalanine hydroxylase (PAH) deficiency. This retrospective longitudinal cohort study investigated metabolic control and monitoring frequency of children with PAH deficiency (≤ 12 years) treated at one of 12 pediatric metabolic centres across Canada. We abstracted data from medical charts and analyzed outcomes by age and diagnostic classification, using mixed effects regression. Of 215 children included in the study, 43% had a chart diagnosis of classic phenylketonuria (PKU); the remainder had a diagnosis of mild PKU or mild hyperphenylalaninemia (grouped as “less severe PAH deficiency”). During the first month of life, blood phenylalanine levels of children with classic PKU reached the target therapeutic range of 120–360 μmol/L at a median age of 15 days, but 74.3% and 32.9% had ≥ 1 and ≥ 3 values below 120 μmol/L, respectively. From age &gt; 1 month to 12 years, mean blood phenylalanine values were 260.6 and 236.7 μmol/L for children with classic PKU and less severe PAH deficiency, respectively, with a trend of increased blood phenylalanine levels with increasing age (<i>p</i> &lt; 0.001). Fewer children with classic PKU (37.2%) versus less severe PAH deficiency (77.9%) had &gt; 60% of values in the therapeutic range, indicating less optimal metabolic control. Frequency of blood phenylalanine testing and communication with metabolic centres decreased with age. Our findings suggest a need to better understand the reasons for blood phenylalanine variability across child age and disease severity in order to inform supports for children with PAH deficiency and their caregivers to maintain metabolic control.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927179","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":"Successful Treatment of Severe Hepatopulmonary Syndrome as a Rare Complication of Zellweger Spectrum Disorder","authors":"Riya Mary Tharakan,&nbsp;Sanjay Rajwal,&nbsp;Bernd C. Schwahn","doi":"10.1002/jmd2.70026","DOIUrl":"https://doi.org/10.1002/jmd2.70026","url":null,"abstract":"<p>We report the case of an 11-year-old girl who developed hepatopulmonary syndrome (HPS) as a rare complication of Zellweger spectrum disorder and was successfully treated with liver transplantation. Our patient presented with neonatal sensorineural hearing loss. Muscular hypotonia, global developmental delay, and pigmentary retinopathy in infancy led to a diagnosis of peroxisomal biogenesis disorder due to compound heterozygous <i>PEX1</i> variants. Despite feeding disorder, poor weight gain, mild liver disease with subclinical coagulopathy, she had a relatively uneventful course, attaining developmental milestones till 7 years of age, when she was noted to have persistent central cyanosis (TcSO₂ 72%) with poor oxygen response. Echocardiogram and CT chest were normal. Liver ultrasound demonstrated mild portal hypertension with a small spleen. An ultrasound bubble test established extracardiac right-left shunting, and perfusion scintigraphy confirmed the diagnosis of HPS. Angiography showed increased portal pressure with normal right atrial pressures, ruling out porto-pulmonary hypertension. Due to the limited prognosis of HPS and inadequate oxygenation on 2 L/min oxygen supplementation, after multidisciplinary discussion, a decision was made to proceed with an orthotopic liver transplant (OLT). Seven months later, she underwent OLT, following which her saturation normalized. At age 11 years, she continues to be clinically stable without oxygen supplementation. HPS being a rare complication of liver disease, is not easily recognized in the pediatric population. OLT proved beneficial in this child with an intermediately severe disorder of peroxisomal biogenesis.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915173","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":"The Utility of High-Sensitivity Troponin to Detect Cardiomyopathy in Patients With Fabry Disease","authors":"Subadra Wanninayake,&nbsp;Tejas Kalaria,&nbsp;Antonio Ochoa-Ferraro,&nbsp;Ashwin Roy,&nbsp;Richard Steeds,&nbsp;Tarekegn Geberhiwot,&nbsp;Charlotte Dawson","doi":"10.1002/jmd2.70008","DOIUrl":"https://doi.org/10.1002/jmd2.70008","url":null,"abstract":"<p>Fabry disease (FD) is an X-linked lysosomal storage disease resulting in lysosomal accumulation of glycosphingolipids in multiple organs. In this study, we (1) compare high-sensitivity cardiac troponins I and T (hs-cTnI and hs-cTnT) as markers of Fabry cardiomyopathy (FC), and (2) evaluate the role of hs-cTn in monitoring early-stage FC to establish if there is a threshold at which significant FC can be reliably excluded. Data were collected retrospectively from clinical records of adults with FD seen in the Inherited Metabolic Disorders service, Birmingham, UK. Patients with cardiac magnetic resonance imaging and concurrent hs-cTnT and/or hs-cTnI measurement(s) were included. FC was defined as the cardiac magnetic resonance imaging features of LVH and/or late gadolinium enhancement and low/pseudonormal T1. One hundred thirty-three patients (male = 54) were included (hs-cTn incidences = 259), 62 patients had significant FC, and 71 did not have FC. hs-cTnI and hs-cTnT were compared by expressing as the fractional ratio (FRTn=hs-cTn concentration/age- and sex-specific 99th percentile). The distribution of FRTnI and FRTnT was not different (median [interquartile range], 0.89 [0.52–2.02] vs. 1.02 [0.47–1.9], <i>p</i> = 0.270), including in patients with and without cardiomyopathy. In differentiating patients with FC from those without, the area under the curve (AUC) for hs-cTn was higher (AUC = 0.974; 95% CI: 0.959–0.990; <i>p</i> &lt; 0.001) than for FRTn (AUC = 0.897) and NT-proBNP (AUC = 0.939). A threshold hs-cTn &lt; 8.5 ng/L was optimal to exclude FC (sensitivity 97.8% and negative predictive value 97.2%) with comparable performance of hs-cTnT and hs-cTnI at this threshold. The degree of serum hs-cTn elevation correlated with the severity of cardiac involvement. We conclude that serial hs-cTn monitoring is superior to NTproBNP for monitoring for early FC. cMRI scans to identify features of FC that are indicators to start treatment can be prioritised to patients with hs-cTn &gt; 8.5 ng/L.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832882","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":"Efficacy of Switching Therapy From Alglucosidase Alfa to Avalglucosidase Alfa on Respiratory Function in Participants With Late-Onset Pompe Disease: A Post Hoc Analysis From the COMET Trial","authors":"Priya S. Kishnani,&nbsp;Matthias Boentert,&nbsp;Stephan Wenninger,&nbsp;Kenneth I. Berger,&nbsp;Jérôme Msihid,&nbsp;Lasair O'Callaghan,&nbsp;Rachida Essadi-Addou,&nbsp;Victor Gallego,&nbsp;Neeraj Singh Rawat,&nbsp;Olivier Huynh-Ba,&nbsp;Jordi Diaz-Manera","doi":"10.1002/jmd2.70033","DOIUrl":"https://doi.org/10.1002/jmd2.70033","url":null,"abstract":"<p>Pompe disease (PD) is a rare, autosomal recessive neuromuscular disorder caused by a deficiency in acid α-glucosidase. In the Phase 3 COMET trial (NCT02782741), respiratory function was examined in participants with late-onset PD randomized to receive enzyme replacement therapy with alglucosidase alfa (ALG; standard of care) or avalglucosidase alfa (AVA; intervention) in the primary analysis period (PAP). The open-label extended treatment period (ETP) provided long-term data on AVA treatment. This post hoc analysis evaluated respiratory outcomes in participants who received ALG in the PAP (Weeks 0–49) and switched to AVA in the ETP (Weeks 49–145). Participants were categorized according to improvement in upright forced vital capacity percent-predicted (FVC) at Week 49. Forty-four participants were included, of whom 20 (45.5%) had ΔFVC &gt; 0% predicted at Week 49. Among ΔFVC &gt; 0% predicted participants, FVC improved during the PAP (estimated slope [SE]: 4.0 (1.1) %/year, <i>p</i> &lt; 0.01), and was maintained following switch to AVA in the ETP (0.1 (0.8) %/year, <i>p</i> = 0.86). For participants with ΔFVC ≤ 0% predicted during the PAP (<i>n</i> = 24; estimated slope [SE]: −3.4 (1.0) %/year, <i>p</i> &lt; 0.01), FVC stabilized following switch to AVA (0.3 (0.7) %/year, <i>p</i> = 0.70). Slopes in measures of respiratory airflow and inspiratory/expiratory muscle strength were consistent with these findings. Similar results were observed using ΔFVC ≥ 3% predicted as a measure of clinically meaningful change. This analysis demonstrates clinically meaningful maintenance in measures of lung volume (FVC) and airflow (forced expiratory volume in 1 s) after switching therapy from ALG to AVA that persists for ≥ 2 years and is independent of prior outcomes with ALG.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832883","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":"Glycine N-Acyltransferase Deficiency due to a Homozygous Nonsense Variant in the GLYAT: A Novel Inborn Error of Metabolism","authors":"Mona Nourbakhsh,&nbsp;Mohammad Miryounesi,&nbsp;Ali Tale,&nbsp;Parvaneh Karimzadeh,&nbsp;Hossein Sadeghi,&nbsp;Mohammad-Reza Ghasemi,&nbsp;Nasrin Alipour,&nbsp;Elham Pourbakhtyaran,&nbsp;Nakisa Hooman,&nbsp;Maryam Razzaghy-Azar,&nbsp;Mitra Nourbakhsh,&nbsp;Lil Klaas,&nbsp;Daniel Schulke,&nbsp;Jörn Oliver Sass","doi":"10.1002/jmd2.70032","DOIUrl":"https://doi.org/10.1002/jmd2.70032","url":null,"abstract":"<p>The enzyme glycine <i>N</i>-acyltransferase (GLYAT) plays a crucial role in detoxifying both xenobiotic and endogenous compounds that contain a carboxylic acid group, such as benzoic acid. Data on the impact of human GLYAT on the glycine conjugation pathway is limited and difficult to determine. In this study, we present a 5.7-year-old girl with gross motor delay first noticed at age 5 months and speech delay evident at the time of diagnosis. To the best of our knowledge, no case of GLYAT enzyme deficiency has been reported to date. Whole exome sequencing (WES) identified a homozygous nonsense variant (NM_201648.3: c.322C&gt;T: p.(Q108Ter)) in the <i>GLYAT</i> that abolished GLYAT activity in vitro. The detected variant was confirmed by Sanger sequencing. The patient was treated with pantothenic acid and a mitochondrial cocktail consisting of coenzyme Q10, vitamins B1, B2, B6, B12, C, folate, and carnitine, together with a low-protein diet, which led to the alleviation of edema and hypotonia and an improvement in her motor function and social interactions. Her serum glycine level was also normalized. This case identifies a novel homozygous nonsense variant in the <i>GLYAT</i>, leading to glycine <i>N</i>-acyltransferase enzyme deficiency and associated developmental delays.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725628","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":"Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): A Case Report With a Complex Biochemical Profile","authors":"Romain Penicaud,&nbsp;Jean-Baptiste Ferron,&nbsp;Xavier Valette,&nbsp;Pierrick Bauduin,&nbsp;Maxime Faisant,&nbsp;Manuel Schiff,&nbsp;Alexandre Nguyen,&nbsp;Fanny Fontaine,&nbsp;Stéphane Allouche","doi":"10.1002/jmd2.70035","DOIUrl":"https://doi.org/10.1002/jmd2.70035","url":null,"abstract":"<p>Three clinical entities of multiple acyl-CoA dehydrogenase deficiency (MADD, OMIM#231680) can be differentiated: two severe neonatal forms and one later-onset form that can manifest in adulthood. The latter typically presents with muscle-related symptoms, such as exercise intolerance and muscle weakness, with an increase in all chain-length acylcarnitine species on the acylcarnitine profile. Here, we report the case of a 33-year-old woman who experienced severe psychiatric issues complicated by an eating disorder resulting in a significant malnutrition a few months before presenting with a profound muscle weakness, fatigue, intermittent ptosis, and a major rhabdomyolysis (creatine kinase (CK) &gt; 15 000 IU/L). Biochemical blood tests, including acylcarnitine profile, urinary organic acid analysis, and in vitro beta-oxidation, were not suggestive of a metabolic disease. Given the absence of an etiology and the worsening health condition of the patient, whole exome sequencing (WES) was performed and revealed two pathogenic variants in the electron transfer flavoprotein dehydrogenase (<i>ETFDH)</i> gene, whose association has not been reported before. Unlike other beta oxidation deficiencies, which have a typical biochemical signature, the diagnosis of MADD was made by genetic analyses, which allowed the introduction of vitamin B2 supplementation and the rapid improvement of symptoms.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657580","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":"Human D-Lactate Dehydrogenase Deficiency: A Case Report in a Young Boy","authors":"T. B. Sloth,&nbsp;M. C. Ørngreen,&nbsp;J. Ek,&nbsp;I. Bache,&nbsp;F. Wibrand,&nbsp;A. M. Lund","doi":"10.1002/jmd2.70039","DOIUrl":"https://doi.org/10.1002/jmd2.70039","url":null,"abstract":"<p>D-lactate is an isomeric form of lactate, which is almost undetectable in the circulation in individuals with normal lactate metabolism. Patients diagnosed with the disease human D-lactate dehydrogenase deficiency present with elevated plasma D-lactate, causing D-lactic acidosis, which can be associated with neurological symptoms. This paper reports a Danish patient presenting with delayed psycho-motor development and metabolic acidosis. Whole genome sequencing (WGS) revealed a homozygous 0.1 Mb loss of the long arm of chromosome 16 involving 3 protein coding genes, <i>CTRB2</i>, <i>ZFP1</i>, and exon 1–7 of the <i>LDHD</i> gene (NM_194436.3c: 1_930del, p.M1_Q310del), which encodes the human D-lactate dehydrogenase enzyme. Metabolic screening of the plasma and urine demonstrated elevated levels of D-lactate. Based on the genetic and biochemical findings, the patient was diagnosed with human D-lactate dehydrogenase deficiency. Biochemical and molecular studies, including WGS, did not disclose any additional pathogenic findings. This report compares the laboratory and clinical findings in our patient with observations in other patients diagnosed with human D-lactate dehydrogenase deficiency described in the literature. The comparison shows that the clinical symptoms vary among patients with pathogenic variants in the <i>LDHD</i> gene, but an elevated level of D-lactate in plasma and urine is found in all patients. Some reported patients had additional diseases, while the boy reported here was most probably solely affected by D-lactate dehydrogenase deficiency, making the clinical picture clearer. Take-home message: Human D-lactate dehydrogenase deficiency can be caused by pathogenic variants of the <i>LDHD</i> gene, and shows a broad phenotypic variability, with some patients only having increased plasma urate/gout and others neurological findings and psycho-motor developmental delay.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647716","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":"A Mild Juvenile Onset Canavan Disease With Atypical Clinical Presentation and MRI Brain Features","authors":"Preeya Rehsi,&nbsp;Ata Siddiqui,&nbsp;Rahul Singh,&nbsp;Obioma Ihezue,&nbsp;Rebecca Halligan","doi":"10.1002/jmd2.70031","DOIUrl":"https://doi.org/10.1002/jmd2.70031","url":null,"abstract":"<p>This case report highlights an atypical presentation of Canavan disease (CD) in a 13-year-old female with intention tremor and fine motor difficulties. Neuroimaging revealed symmetrical changes in various brain regions initially suggesting a neurometabolic or mitochondrial disorder. However, further investigations, including biochemical analysis and whole genome sequencing, confirmed a diagnosis of CD. Unlike classical presentations, this case exhibited milder symptoms and unusual MRI findings, contributing to the expanding clinical and radiological spectrum of CD. The importance of recognizing such atypical presentations is emphasized for accurate diagnosis and management of CD.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606643","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}