JIMD reports最新文献

{"title":"Clinical Outcomes and Correlation With Biochemical Control in Hydroxocobalamin-Treated Patients With Early-Onset Cobalamin C Disease.","authors":"Arthavan Selvanathan, Ashley Hertzog, Jacqui Russell, Rosie Junek, Carolyn Ellaway, Kate Lichkus, Adviye Ayper Tolun, Kaustuv Bhattacharya","doi":"10.1002/jmd2.70091","DOIUrl":"https://doi.org/10.1002/jmd2.70091","url":null,"abstract":"<p><p>Cobalamin C (cblC) disease is the most common disorder of Vitamin B12 activation. The early-onset form presents within the first few months of life, with some patients identified through newborn screening (NBS). However, despite early detection and optimal treatment, patient outcomes remain poor, with intellectual impairment and progressive visual loss in the majority. We reviewed a cohort of 10 patients with cblC disease, all identified either by NBS or a neonatal clinical presentation. We reviewed their biochemical control and correlated this with clinical progress and treatment. The majority of the cohort (including four asymptomatic patients) was identified through NBS and had genotypes predictive of early-onset disease. Clinical outcomes improved with standard-of-care treatment (hydroxocobalamin, betaine, and folinic acid) but were suboptimal, with both neurocognitive (6/10) and ophthalmological manifestations (10/10) occurring in most patients. One patient died at 5 months of age, and it is unclear whether this was related to cblC disease or not. Across over 250 timepoints from 9 patients, there was minimal correlation between cumulative intramuscular hydroxocobalamin (OHCbl) dose and biomarkers, including methylmalonic acid (<i>r</i> ² = 0.0031) and total homocysteine (<i>r</i> ² = 0.2858) levels. This study provides comprehensive, longitudinal biochemical, and clinical follow-up of patients with cblC disease treated from soon after birth, often presymptomatically. Our findings corroborate previous observations regarding the lack of correlation of current biomarkers, both with disease progression and with standard (< 0.3 mg/kg/day) hydroxocobalamin dosing. Further investigation of the clinical impact of early high-dose OHCbl treatment is needed in larger cohorts of patients.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 ","pages":"e70091"},"PeriodicalIF":1.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772130","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":"Antenatal Presentation of MRPS22-Related Mitochondrial Disease Confirmed With Rapid Proteomics.","authors":"Liana N Semcesen, Megan Ball, Daniella H Hock, Juliet Kaye, Aimee Woods, Lucas De Jong, John Christodoulou, David R Thorburn, Alison G Compton, David A Stroud, Jan Liebelt","doi":"10.1002/jmd2.70092","DOIUrl":"https://doi.org/10.1002/jmd2.70092","url":null,"abstract":"<p><p><i>MRPS22</i>-related mitochondrial disease (MIM#611719) is a rare autosomal recessive disorder caused by defects in the mitochondrial ribosomal protein S22, a component of the small mitoribosomal subunit essential for mitochondrial translation. Of the few reported cases, most present antenatally with a severe phenotype, conveying a poor prognosis. We describe a fetus with severe antenatal-onset <i>MRPS22</i>-related mitochondrial disease and the use of multi-omics in the molecular diagnosis. A primigravida underwent termination of pregnancy following identification of multiple congenital anomalies (hydrops fetalis, microcephaly, corpus callosal agenesis, periventricular cysts and cardiac hypertrophy) on ultrasound at 20 + 2 weeks' gestation, confirmed on fetal magnetic resonance imaging. Trio genome sequencing revealed compound heterozygous variants in <i>MRPS22</i> (NM_020191.4: c.509G>A; p.(Arg170His) and c.565C>G; p.(Arg189Gly)). Rapid proteomic analysis demonstrated destabilisation of the small mitoribosomal subunit and combined reduction of OXPHOS complexes, supporting the pathogenicity of the variants. This case consolidates the antenatal phenotype of severe MRPS22-related disease and highlights the importance of considering mitochondrial disease in the differential diagnosis of congenital anomalies, especially hydrops fetalis and corpus callosum anomalies. This study provides evidence for the utility of multi-omic approaches (trio genome sequencing, proteomics) in confirming variant pathogenicity following pregnancy loss, enabling accurate diagnosis, and informing reproductive counselling for affected families.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 ","pages":"e70092"},"PeriodicalIF":1.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772054","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":"Should PNPO Deficiency Be Treated In Utero? Clinical Findings From Prenatal Pyridoxine Therapy.","authors":"Chloé de Puyraimond, Samia Pichard, Muriel Girard, Julian Delanne, Laurence Faivre, Apolline Imbard, Amandine Baurand, Jean-François Benoist, Philippa B Mills, Peter T Clayton, Manuel Schiff","doi":"10.1002/jmd2.70086","DOIUrl":"https://doi.org/10.1002/jmd2.70086","url":null,"abstract":"<p><p>Pyridox(am)ine-5'-phosphate oxidase (PNPO) deficiency is characterized by early-onset epileptic encephalopathy refractory to standard antiseizure medications. It is caused by variants in the <i>PNPO</i> gene, resulting in deficient PNPO enzyme activity, which normally converts pyridoxine-5'-phosphate and pyridoxamine-5'-phosphate (two vitamers of vitamin B6) into the active cofactor, pyridoxal-5'-phosphate (PLP). Treatment relies on PLP or pyridoxine in some cases. Long-term outcomes remain suboptimal. We describe two cases of unrelated children treated with vitamin B6 (pyridoxine) in utero: one with a confirmed prenatal PNPO diagnosis and one at risk due to family history but ultimately unaffected. In utero pyridoxine, combined with early postnatal PLP treatment, allowed excellent seizure control and normal neurodevelopment in the long term. Notably, our first patient, treated from birth, is now 10 years old, representing the oldest reported PNPO-deficient individual treated from birth. Case 2 highlights the safety of prenatal B6 supplementation even in unaffected fetuses. These observations support prenatal pyridoxine supplementation as a safe and potentially beneficial strategy in at-risk PNPO pregnancies.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 3","pages":"e70086"},"PeriodicalIF":1.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772072","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":"Long-Term Safety and Efficacy of Pegvaliase in Japanese Adults With Phenylketonuria: Final Results of a Phase III Trial","authors":"Yoko Nakajima,&nbsp;Mika Ishige,&nbsp;Tetsuya Ito,&nbsp;Takashi Hamazaki,&nbsp;Mitsuhiro Kuwahara,&nbsp;Lawrence Lee,&nbsp;Haruo Shintaku","doi":"10.1002/jmd2.70084","DOIUrl":"10.1002/jmd2.70084","url":null,"abstract":"<p>Phenylketonuria (PKU) is an inborn error of metabolism leading to phenylalanine (Phe) accumulation and consequent neurological, neurocognitive, and psychiatric symptoms. Pegvaliase, a pegylated recombinant phenylalanine ammonia lyase that metabolizes Phe, effectively reduced blood Phe in phase III studies in the United States. This multicenter, open-label, phase III study (jRCT2080224573) evaluated efficacy and safety of up to 4 years of pegvaliase treatment in 12 adult Japanese participants with PKU (blood Phe &gt; 600 μmol/L). Subcutaneous pegvaliase followed an induction/titration/maintenance dosing regimen up to a maximum of 60 mg/day. After Week 52, diet and pegvaliase dose could be adjusted if blood Phe was ≤ 360 μmol/L. Mean (standard deviation [SD]) treatment duration was 166.4 (66.5) weeks. At Week 192 (<i>n</i> = 10), mean (SD) blood Phe was 296.2 (430.7) μmol/L, a 71.2% decrease from baseline, and daily protein intake from intact and medical food was 49.9 (21.4) g (68.0% increase) and 7.6 (16.2) g (64.2% decrease), respectively. All participants had ≥ 1 treatment-emergent adverse event (TEAE) during induction/titration, most commonly injection site erythema and injection site swelling (83.3% each); nine of 10 had a TEAE during maintenance. Of 395 TEAEs recorded during maintenance, 82 occurred between the 2-year interim analysis and the 4-year final analysis. One serious TEAE (allergic arthritis) was considered pegvaliase related. The exposure-adjusted rate of pegvaliase-related events was 17.0 per person-year (41.2 during induction/titration, 8.9 during maintenance). Pegvaliase effectively lowered blood Phe in Japanese participants with PKU, with no new safety issues with long-term treatment, and many participants were able to liberalize their diet.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673590","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":"Unifying the Communities of Early-Onset Glycogen Storage Disease Type IV and Adult Polyglucosan Body Disease Through a Genetic Prevalence Study of GBE1-Related Disease","authors":"Rebecca L. Koch,&nbsp;H. Orhan Akman,&nbsp;Erin Chown,&nbsp;Deberah Goldman,&nbsp;Jeff Levenson,&nbsp;Qing Lu,&nbsp;Lindsay T. Michalovicz Gill,&nbsp;Matthew Morgan,&nbsp;Jennifer L. Orthmann-Murphy,&nbsp;Natacha T. Pires,&nbsp;Rebecca Reef,&nbsp;Harriet Saxe,&nbsp;Moriel Singer-Berk,&nbsp;Samantha Baxter","doi":"10.1002/jmd2.70080","DOIUrl":"10.1002/jmd2.70080","url":null,"abstract":"<p>Glycogen storage disease type IV (GSD IV) is an autosomal recessive disorder caused by pathogenic variants in <i>GBE1</i>, resulting in deficient glycogen branching enzyme (GBE) activity and formation of abnormal glycogen (“polyglucosan”). GSD IV manifests across a spectrum of clinical dimensions—including hepatic, neurologic, muscular, and cardiac involvement—which vary in severity. The early-onset forms, historically referred to as Andersen disease, present at different stages ranging from in utero to adolescence. The adult-onset form, referred to as adult polyglucosan body disease (APBD), typically presents in middle to late adulthood. To date, no epidemiological study of GSD IV has been performed. Understanding the global prevalence of GSD IV is critical to increase disease awareness, improve diagnostic rates, inform therapeutic development, and engage pharmaceutical companies. In collaboration with the Rare Genomes Project at the Broad Institute of MIT and Harvard and the APBD Research Foundation, this study curated variants in <i>GBE1</i> and calculated prevalence across nine genetic ancestry groups. The estimated global carrier frequency of GSD IV is 1 in 243 individuals, and the global genetic prevalence is 1 in 235 784 individuals. Based on the 2024 world population, the estimated number of affected individuals with GSD IV is approximately 34 800. These estimates highlight a significant underdiagnosis of GSD IV and underscore the urgent need for increased awareness of this metabolic disorder. This model of collaboration between researchers, patient advocacy organizations, and genetic data sharing programs provides a framework for estimating the prevalence of other rare diseases in the global population.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633425","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":"Real-World Effectiveness and Safety of Pegzilarginase Treatment in Arginase 1 Deficiency","authors":"Anaïs Brassier,&nbsp;Alina Arion,&nbsp;Jean-Baptiste Arnoux,&nbsp;Magalie Barth,&nbsp;Dries Dobbelaere,&nbsp;Magali Gorce,&nbsp;Michael Grövdal,&nbsp;Cécile Laroche,&nbsp;Olivia Rime,&nbsp;Manuel Schiff,&nbsp;Mattias Rudebeck","doi":"10.1002/jmd2.70081","DOIUrl":"10.1002/jmd2.70081","url":null,"abstract":"<p>Pegzilarginase is the first disease-modifying drug for arginase 1 deficiency. In clinical trials, pegzilarginase effectively normalised plasma arginine (pArg), which was associated with clinically relevant improvements in neuromotor outcomes. We report from a French early access scheme the first report on experience from pegzilarginase therapy outside a clinical trial. Sixteen patients were started in the programme between September 2022 and September 2024. Six had previously participated in a clinical trial (PCT) and 10 were treatment naïve (TN). Clinical data was collected at baseline, after 3 months, and then 6-monthly. Mean pegzilarginase exposure was 78.9 weeks. Fourteen patients had been treated for ≥ 12 months. At the 3-month follow-up, mean pArg had dropped from 430 to 128 μmol/L (70%) for the TN group and from 168 to 107 μmol/L (36%) for the PCT group. Interestingly, one patient discontinued after 69 weeks of therapy due to absence of decrease of pArg despite stepwise increase of dose. After discontinuation of pegzilarginase, the presence of anti-drug antibodies (ADAs) was confirmed. For the whole cohort, average daily intake of dietary protein increased from 0.61 to 0.91 g/kg/day during the first 12 months (<i>p</i> = 0.02). No firm conclusions could be drawn from quality-of-life data, but trends were positive. In conclusion, our results are in line with what has been previously reported from clinical trials.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147585177","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":"Alkaline Phosphatase and Infantile GM1 Gangliosidosis: A Simple Biomarker for a Complex Disease?","authors":"Laura Fiori,&nbsp;Massimiliano Turzi,&nbsp;Veronica Maria Tagi,&nbsp;Laura Asnaghi,&nbsp;Eleonora Bonaventura,&nbsp;Davide Tonduti,&nbsp;Luigina Spaccini,&nbsp;Laura Assunta Saielli,&nbsp;Chiara Montanari,&nbsp;Francesca Cairello,&nbsp;Savina Mannarino,&nbsp;Matilde Ferrario,&nbsp;Alessandra Del Longo,&nbsp;Marcello Napolitano,&nbsp;Andrea Righini,&nbsp;Michela Semeraro,&nbsp;Anna Venerando,&nbsp;Martina Miceli,&nbsp;Elvira Verduci,&nbsp;Gianvincenzo Zuccotti","doi":"10.1002/jmd2.70075","DOIUrl":"10.1002/jmd2.70075","url":null,"abstract":"<p>GM1 gangliosidosis is a lysosomal storage disease (LSD) caused by β-galactosidase deficiency, characterized by the accumulation of gangliosides in various tissues. Among different GM1 forms (infantile form, late-infantile and juvenile form, and late-onset form), the infantile form is the most severe: despite an early clinical onset with rapid neurodegeneration, coarse face, abdominal visceromegaly and skeletal abnormalities, the diagnosis is usually delayed, given the lack of recognized early disease-specific markers. We report the case of a newborn presenting with mild edema of hands and feet, mild transient hypoalbuminemia and isolated hyperphosphatasemia at three weeks of life. The first cardiological evaluation showed mild mitral regurgitation. Despite the absence of neurological symptoms, organomegaly, or a coarse face, the turgid consistency of the limbs, together with mitral regurgitation and persistent hyperphosphatasemia, led to multiorgan investigations with discovery of bilateral cherry-red spots and a beak-shaped lumbar vertebra. The cardiological follow-up revealed a dysplastic mitral valve. In the suspicion of a lysosomal disease, biochemical investigations were planned. An altered profile of urinary oligosaccharides, along with low β-galactosidase activity in leukocytes, led to the diagnosis of infantile GM1 gangliosidosis at 3 months of age. The <i>GLB1</i> gene analysis confirmed the diagnosis. Genetic testing for GLB1 should be considered in cases of persistent hyperphosphatemia, especially if it is associated with any other clinical indicator of GM1, such as limb edema.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377416","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":"Quantitative Succinylacetone Measurement by Gas Chromatography-Tandem Mass Spectrometry (GC–MS/MS) Facilitates Diagnosis, Monitoring, and Characterization of Tyrosinemia Type 1 and Other Hypersuccinylacetonemias","authors":"Denis Cyr,&nbsp;Bruno Maranda,&nbsp;Paula J. Waters","doi":"10.1002/jmd2.70078","DOIUrl":"10.1002/jmd2.70078","url":null,"abstract":"<p>Tyrosinemia type 1 (HT1), due to deficient activity of fumarylacetoacetate hydrolase, causes accumulation of succinylacetone (SA). SA concentrations in urine and plasma of untreated HT1 patients are typically several thousand-fold higher than normal, hence are readily recognized by traditional diagnostic methods in most cases. However, quantitation of SA in the nanomolar range is important for monitoring patients treated with nitisinone, for identifying attenuated or atypical forms of HT1, and for confirmation or refutation of the diagnosis of HT1 following a positive newborn screen. Our laboratory, a reference centre for diagnosis and monitoring of HT1, previously assayed SA by gas chromatography–mass spectrometry (GC–MS). Three years ago, we upgraded this method by transferring it to a new triple quadrupole technology (GC–MS/MS). A stable isotope dilution process is used, with sample treatment consisting of an oximation step followed by a single liquid–liquid extraction then trimethylsilyl derivatization. Quantitation is based on intensities of the ion transitions m/z 620 → 181 for SA and 625 → 186 for the internal standard. Method validation demonstrated enhanced analytical specificity and sensitivity, with good precision and accuracy. Using GC–MS/MS instead of GC–MS allowed a limit of quantitation of 1 nmol/L while decreasing the required specimen volumes, as well as reducing the number of sample processing steps, chromatographic run time, and instrument maintenance. This assay facilitates laboratory diagnosis and monitoring of HT1, permits identification and characterization of other hypersuccinylacetonemias including maleylacetoacetate isomerase deficiency, and is also a valuable tool for research studies using animal models and cellular models of HT1.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325950","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 Outcomes and Management in Late Diagnosed Siblings Affected With Attenuated GSD Ib","authors":"Gregory Lynch,&nbsp;Alison Woodall,&nbsp;Charlotte Dawson,&nbsp;Philip Newsome,&nbsp;Maria Veiga-da-Cunha,&nbsp;Karolina M. Stepien","doi":"10.1002/jmd2.70079","DOIUrl":"10.1002/jmd2.70079","url":null,"abstract":"<p>Glycogen storage disease 1b (GSD1b) typically presents in early infancy with poor fasting tolerance, hepatomegaly, and neutropenia. We report two siblings who were diagnosed with GSD1b in adulthood. Both had a normal fasting tolerance throughout childhood and, as adults, were able to fast for at least 16 h without developing hypoglycaemia. The older sibling developed nodular cirrhosis during adolescence. The younger sibling exhibited a more pronounced metabolic phenotype, including hyperuricaemia leading to recurrent gout and nephrolithiasis. He experienced occasional episodes of mild neutropenia that were corrected with empagliflozin treatment. To our knowledge, these represent the first reported patients with GSD1b presenting in adulthood with non-hypoglycaemic complications of the disease and without overt neutropenia or neutrophil dysfunction.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325890","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":"Abnormal Newborn Screening Resembling Carnitine Palmitoyltransferase 1a Deficiency in Three Patients With COASY Protein Associated Neurodegeneration","authors":"Matthew Lynch,&nbsp;Sophie Manoy,&nbsp;Claire Murray,&nbsp;Geoff Wallace,&nbsp;Nolette Pereira,&nbsp;Ricky Price,&nbsp;Anita Inwood,&nbsp;Jim McGill,&nbsp;David Coman","doi":"10.1002/jmd2.70066","DOIUrl":"10.1002/jmd2.70066","url":null,"abstract":"<p><i>COASY</i> protein associated neurodegeneration is a rare, progressive autosomal recessive neuroferritinopathy due to pathogenic mutations in the <i>COASY</i> gene, coding for the mitochondrial located coenzyme A synthase. Clinical manifestations include seizures, progressive spasticity, dystonia, neuropathy, cognitive decline and neuropsychiatric abnormalities. Both foetal and childhood onset phenotypes are described. We report three patients with <i>COASY</i> protein associated neurodegeneration who were identified on newborn screening with a dried bloodspot acylcarnitine pattern consistent with carnitine palmitoyltransferase 1a deficiency, that is, an elevated ratio of free carnitine (C0) to the sum of palmitoylcarnitine (C16) and octanoylcarnitine (C18):[C0/(C16+C18)]. Two siblings, who died in infancy, displayed neurological features from birth, with magnetic resonance imaging of the brain displaying immature cortical sulcation, parenchymal atrophy and pontocerebellar hypoplasia. The third patient presented with global developmental delay, pyramidal signs and seizures with brain magnetic resonance imaging at age 15 months demonstrating a thin corpus callosum, symmetric diffusion restriction throughout the basal ganglia and evidence of deposition in the globus pallidus. This report demonstrates that phenotypes of <i>COASY</i> protein associated neurodegeneration should be included in the differential diagnosis of dried blood spot acylcarnitine pattern suggestive of carnitine palmitoyltransferase 1a deficiency and may represent new potential for early diagnosis.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325909","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}