JIMD reports最新文献

{"title":"A Pilot Study of Bone Marrow Transplantation in a GALT-Null Rat Model of Classic Galactosemia","authors":"Shauna A. Rasmussen,&nbsp;Madelyn M. Seemiller,&nbsp;Ingrid Smith,&nbsp;Madeleine Wilson,&nbsp;Jennifer M. I. Daenzer,&nbsp;Keenan Wiggins,&nbsp;Judith L. Fridovich-Keil","doi":"10.1002/jmd2.70037","DOIUrl":"https://doi.org/10.1002/jmd2.70037","url":null,"abstract":"<p>Classic galactosemia (CG) is a rare inborn error of metabolism with substantial unmet medical need. Early detection, often by population newborn screening, enables immediate and life-long dietary restriction of galactose, which is the current standard of care. This treatment minimizes or prevents the potentially lethal acute symptoms of disease in infants but fails to prevent the long-term developmental complications experienced by most patients later in childhood. Many possible approaches to improved intervention have been proposed, ranging from small molecule inhibitors or effectors to chaperones to DNA or RNA-based gene therapy, among others. Here, we describe the results of a pilot study testing the potential efficacy of GALT+ bone marrow transplantation (BMT) as a candidate intervention in a GALT-null rat model of CG. Specifically, we pre-treated adolescent GALT-null rats with busulfan for myeloablation and then administered major histocompatibility complex (MHC)-matched GFP+ bone marrow cells harvested from either GALT+ or GALT-null donors. Successful engraftment of GALT+ but not GALT-null cells resulted in &gt; 50% wild-type levels of GALT activity in red blood cells (RBC) and normalized RBC galactose-1-phosphate, a biomarker commonly followed in CG patients. However, GALT activity and galactose metabolites in both liver and brain samples remained essentially unchanged, demonstrating that successful GALT+ BMT in adolescent GALT-null rats was not protective of other tissues.</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/jmd2.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606644","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":"Mitochondrial DNA Pathogenic Variant Prevalence in Primary Mitochondrial Disease Patients With African (L) Mitochondrial Genome Haplogroups","authors":"Surita Meldau,&nbsp;Elizabeth M. McCormick,&nbsp;Ibrahim George-Sankoh,&nbsp;Gillian T. Riordan,&nbsp;Kashief Khan,&nbsp;Laura E. MacMullen,&nbsp;Shrinav Dawlat,&nbsp;Dee Blackhurst,&nbsp;Marni J. Falk,&nbsp;Joanna L. Elson","doi":"10.1002/jmd2.70036","DOIUrl":"https://doi.org/10.1002/jmd2.70036","url":null,"abstract":"<p>Primary mitochondrial diseases (PMD) are caused by pathogenic variants in over 350 genes, 37 of which are located in mitochondrial DNA (mtDNA). While more than 100 mtDNA variants have confirmed disease associations, there are few reports of mtDNA-related PMD in patients with African heritage, even in well-studied populations. We investigated the frequency of pathogenic mtDNA variants in African L-haplogroups in patients with confirmed PMD from two diagnostic cohorts. Data from genetically confirmed mtDNA-related cases were extracted from existing databases at the National Health Laboratory Service Inherited Metabolic Disease Laboratory in South Africa (SA), and the Children's Hospital of Philadelphia (CHOP) Mitochondrial Medicine Frontier Program (USA). Mitochondrial genome haplogroup context was recorded from existing sequence report data. Stored DNA from the remaining cases was sequenced for mitochondrial genome haplogroup determination. Haplogroup context was obtained for 82 SA and 165 CHOP PMD cases. Sixty-two (47 SA; 15 USA) PMD cases from at least 50 maternal lineages were found to carry L Haplogroups. Unique L sub-haplogroups were identified in 11 (9 SA, 2 USA) families with the m.3243A&gt;G MELAS variant, 6 SA families with the m.11778G&gt;A LHON variant, and 20 (15 SA, 5 USA) cases with single large-scale mtDNA deletions (4 of whom had the 4977 bp common deletion). Several additional well-documented mtDNA pathogenic variants were identified in L-haplogroup context. PMD patient clinical features correlated closely with those described in other haplogroup cohorts. This study demonstrates that common pathogenic mtDNA variants occur in the context of multiple African mtDNA lineages. Disproportionately low diagnostic rates highlight ongoing diagnostic inequalities affecting those on the African continent and African patients globally.</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/jmd2.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606655","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":"Cardiac Transplantation Does Not Improve Exercise Tolerance, Muscle Mass, or Substrate Metabolism in Barth Syndrome","authors":"W. Todd Cade,&nbsp;Kathryn L. Bohnert,&nbsp;Linda R. Peterson,&nbsp;Lisa de las Fuentes,&nbsp;Emily Poehlein,&nbsp;Cynthia L. Green,&nbsp;Christina A. Pacak,&nbsp;Barry J. Byrne,&nbsp;Dominic N. Reeds,&nbsp;Adil Bashir,&nbsp;Brian Feingold,&nbsp;Carolyn Taylor","doi":"10.1002/jmd2.70034","DOIUrl":"https://doi.org/10.1002/jmd2.70034","url":null,"abstract":"<p>Barth syndrome (BTHS) is a rare X-linked recessive disorder characterized by mutations in the TAFAZZIN gene, leading to mitochondrial dysfunction, cardioskeletal myopathy, neutropenia, exercise intolerance, and growth delay. While cardiac transplantation can improve heart function in BTHS patients, the metabolic effects of this procedure remain poorly understood. This study aimed to compare skeletal muscle morphology, substrate metabolism, energetics, and exercise tolerance in individuals with BTHS who had undergone cardiac transplantation (BTHS-T) versus BTHS patients without transplantation (BTHS-noT) and healthy controls. Six (<i>n</i> = 6) BTHS-T participants (3 adolescents, 3 adults) were compared with <i>n</i> = 29 BTHS-noT and <i>n</i> = 28 healthy controls. All participants underwent graded exercise testing, echocardiography, body composition analysis, and clinical metabolism studies, including ³¹P-MRS to assess mitochondrial energetics. No significant differences were observed in fat-free mass between BTHS-T participants and BTHS-noT. Exercise capacity (V̇O_2peak) was significantly lower in both BTHS groups compared to controls, with lower heart rate responses during peak exercise. In addition, plasma lactate was higher in both BTHS groups compared to healthy controls. Skeletal muscle energetics showed slower phosphocreatine recovery and reduced ATP production in BTHS participants, regardless of cardiac transplantation status. Findings suggest while cardiac transplantation in BTHS may improve heart function, it may not normalize skeletal muscle mass and energetics, metabolic abnormalities, and exercise intolerance. The study enhances our understanding of long-term metabolic consequences of BTHS and potential limitations of cardiac transplantation in ameliorating these dysfunctions. Further research is needed to explore targeted therapies to address underlying metabolic abnormalities in BTHS patients.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573672","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 Management and Clinical Outcomes of Pregnancy in a Female With Glycogen Storage Disease Type IIIA Caused by Rare Variant","authors":"Nuria Puente-Ruiz,&nbsp;Saru Palaniappan,&nbsp;Alison Woodall,&nbsp;Robert Cooper,&nbsp;Allyson Terry,&nbsp;Andrew Oldham,&nbsp;Abigail Rousseau,&nbsp;Christopher Campbell,&nbsp;Pradeep Vasudevan,&nbsp;Karolina M. Stepien","doi":"10.1002/jmd2.70030","DOIUrl":"https://doi.org/10.1002/jmd2.70030","url":null,"abstract":"<p>Glycogen storage disease type III (GSD III) is an inborn error of carbohydrate metabolism with an autosomal recessive inheritance pattern. Phenotypically, patients can manifest a broad clinical spectrum. Most patients affected with GSD IIIA (85%) have a non-functional GDE enzyme primarily affecting the liver and cardiac/skeletal muscle (Type IIIA). Initial clinical manifestations of GSD IIIA present in the first year of life. Presentation is very similar to GSD type I. Up to 98% of children affected have hepatomegaly, hypoglycaemia (53%) with marked ketosis (34%), short stature (49%), delayed puberty, and frequent infections (17%). In adulthood, they may have cirrhosis, adenomas, or hepatocarcinomas (11%), cardiomyopathy (58%) and myopathy (34%). Pregnancy has been documented in women with GSD III. Nutritional requirements are increased during pregnancy, especially in the third trimester. We report the management of a woman with GSD IIIA found to be compound heterozygous for two pathogenic AGL variants, c.798C&gt;G p.(Tyr266Ter) and c.4258_4259ins? p.(Asp1420fs), who had a planned pregnancy. Cardiac outcomes are also described/discussed.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537038","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":"HMG-CoA Synthase-2 Deficiency: Neonatal Hyperammonemic Coma and Abnormal Metabolic Screening Resembling Maple Syrup Urine Disease","authors":"Hathaipat Vaseenon,&nbsp;Thipwimol Tim-Aroon,&nbsp;Vitchayaporn Emarach Saengow,&nbsp;Areeporn Sangcakul,&nbsp;Parith Wongkittichote,&nbsp;Arthaporn Khongkraparn,&nbsp;Duangrurdee Wattanasirichaigoon","doi":"10.1002/jmd2.70028","DOIUrl":"https://doi.org/10.1002/jmd2.70028","url":null,"abstract":"<p>Mitochondrial HMG-CoA synthase-2 (HMGCS2) deficiency is characterized by hypoketotic hypoglycemia, metabolic acidosis, hepatomegaly, and encephalopathy with onset between 3 and 36 months of age. Approximately 50 cases were reported worldwide. We describe two patients with HMGCS2 deficiency. Patient 1 presented on day of life 7 with a sepsis-like condition, coma, metabolic acidosis, and marked elevation of ammonium level at 1081 μmol/L. Metabolic screening demonstrated elevated valine and leucine/isoleucine concentrations, resembling maple syrup urine disease (MSUD). The patient received a blood exchange transfusion, which lowered the ammonium level to 92 μmol/L. Urine organic acid analysis did not confirm MSUD. At 1 year and 4 months, the patient experienced acute decompensation again. Exome sequencing revealed a homozygous <i>HMGCS2</i> variant, c.1502G&gt;C (p.Arg501Pro). Patient 2, an older sibling of Patient 1, was healthy but diagnosed through genetic testing. Both patients exhibited abnormal biochemical profiles, including dicarboxylic aciduria and increased urinary excretion of 4-hydroxy-6-methyl-2-pyrone (4-HMP) after 8 h of fasting, suggesting that a clinically asymptomatic patient, like Patient 2, may eventually develop acute decompensation. Therefore, preemptive treatment with fasting avoidance with or without <span>l</span>-carnitine during intercurrent illness should be advised. The present cases were the second and third patients of p.Arg501Pro homozygosity. The elevated branched-chain amino acids in the metabolic screening (without including alloisoleucine) and the described organic acid profile can be found during the catabolic state, resembling MSUD, and severe hyperammonemia is an uncommon phenotype and an exception to neonatal decompensation in HMGCS2 deficiency. Our findings demonstrated intrafamilial variability and expanded the clinical and biochemical spectrum of HMGCS2 deficiency.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339112","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":"Investigating the Utility of Leukocyte Sialic Acid Measurements in Lysosomal Free Sialic Acid Storage Disorder","authors":"Marya S. Sabir,&nbsp;Laura Pollard,&nbsp;Lynne Wolfe,&nbsp;David R. Adams,&nbsp;Carla Ciccone,&nbsp;Petcharat Leoyklang,&nbsp;Frances M. Platt,&nbsp;Marjan Huizing,&nbsp;William A. Gahl,&nbsp;May Christine V. Malicdan","doi":"10.1002/jmd2.70029","DOIUrl":"https://doi.org/10.1002/jmd2.70029","url":null,"abstract":"<p>Lysosomal free sialic acid storage disorder (FSASD) is a rare, multisystem neurodegenerative disease caused by biallelic pathogenic variants in <i>SLC17A5</i>, encoding sialin. FSASD is characterized by aberrant accumulation of unconjugated “free” sialic acid (Neu5Ac) within lysosomes. Depending on the specific genetic variants, affected individuals may present with either a rapidly fatal disease or progressive neurodegeneration. While skin fibroblasts have traditionally been used for diagnosis and research, the use of leukocytes in FSASD remains underexplored. This study examined Neu5Ac levels in leukocytes from three individuals with FSASD carrying distinct <i>SLC17A5</i> variants. The levels in affected individuals were compared to three different groups: (1) the unaffected biological parents of each case; (2) subjects for whom 14 distinct lysosomal storage disorders (LSDs) were excluded based on enzyme analysis (<i>n</i> = 11); and (3) participants with a confirmed LSD diagnosis, as determined by enzyme analysis (<i>n</i> = 9). Individuals with FSASD exhibited significantly higher levels of free Neu5Ac compared to their unaffected biological parents (36-fold), LSD-negative subjects (22-fold), and individuals with other LSDs (49-fold). Although total Neu5Ac levels showed a non-significant trend toward an increase in FSASD (1.3-fold), this was primarily due to elevated free Neu5Ac, as bound Neu5Ac was slightly decreased in the leukocytes of FSASD cases relative to their unaffected parents. Overall, these findings highlight leukocytes as a valuable, minimally invasive cellular model for FSASD, offering an alternative, reliable diagnostic tool and a potential platform for monitoring therapeutic responses in future intervention trials.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299738","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":"Exploratory Study on the Challenges of Newborn Screening for Lysosomal Storage Disorders Emphasizes the Need for Multitier Testing and Collaborative Approaches to Management","authors":"A. Terrell,&nbsp;K. Sapp,&nbsp;B. Graham,&nbsp;M. McPheron,&nbsp;L. Wetherill","doi":"10.1002/jmd2.70027","DOIUrl":"https://doi.org/10.1002/jmd2.70027","url":null,"abstract":"<p>Innovative treatments have allowed the introduction of conditions such as lysosomal storage disorders (LSDs) to newborn screening (NBS). This study explored the challenges healthcare providers faced with the addition of LSDs to NBS and identified adjustments that minimized the burden of such challenges. An online survey was distributed to healthcare providers with experience working with patients with LSDs. The most common <i>anticipated</i> challenges were interpreting NBS results (75%) and having adequate screening protocols (63%). <i>After the addition of LSDs</i>, interpretation of newborn screen results (64%) remained a challenge, but adequate screening protocols were less frequent (25%). Collaboration of care with additional subspecialty providers was the most common change in clinic structure (68%) and individual practice (54%) after the addition of LSDs to NBS. Given the interpretation of results remained a challenge most providers faced, we advocate the implementation of multitier screening protocols is key to improving sensitivity and specificity of NBS for LSDs. This allows for the identification of at-risk infants and provides clarity on expected phenotypes and healthcare needs. These results indicate collaboration between healthcare providers is a key factor in providing optimal care. The findings of this study may benefit clinics that are implementing NBS for LSDs as the adoption of these practices preemptively may reduce the burden of that challenge.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299739","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":"Placenta Pathologies in Two Patients With Glycogen Storage Disease Type Ia and Preeclampsia","authors":"V. Laufs,&nbsp;A. Hasenburg,&nbsp;M. A. Busch,&nbsp;F. Lang,&nbsp;D. Macchiella,&nbsp;E. Mildenberger,&nbsp;L. Seidmann,&nbsp;J. B. Hennermann","doi":"10.1002/jmd2.70025","DOIUrl":"https://doi.org/10.1002/jmd2.70025","url":null,"abstract":"<p>Little is known about pregnancies and placental changes in women with glycogen storage disease type Ia (GSD Ia). We report on two primipara with GSD Ia who both developed preeclampsia and whose newborns were small for gestational age. Both placentas showed sonomorphological and macroscopical abnormalities. Disease-specific histological features could not be identified, which should prompt further research.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273109","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 and Developmental Outcomes After 50 Years of Newborn Bloodspot Screening for Classical Galactosaemia in the Republic of Ireland","authors":"D. Pereira,&nbsp;E. Loftus,&nbsp;C. E. Thompson,&nbsp;F. Boyle,&nbsp;J. McNulty,&nbsp;R. Boruah,&nbsp;E. Crushell,&nbsp;C. Howard,&nbsp;J. Hughes,&nbsp;A. A. Monavari,&nbsp;E. P. Treacy,&nbsp;A. Beegan,&nbsp;N. Jordan,&nbsp;Y. Rogers,&nbsp;A. Collins,&nbsp;J. J. Brady,&nbsp;M. Elsammak,&nbsp;P. D. Mayne,&nbsp;I. Knerr","doi":"10.1002/jmd2.70022","DOIUrl":"https://doi.org/10.1002/jmd2.70022","url":null,"abstract":"<p>Classical Galactosaemia (CG) is an inborn error of carbohydrate metabolism. In untreated neonates, CG leads to a multi-organ toxicity with life-threatening symptoms. Newborn Screening for CG began in the Republic of Ireland in 1972. In Ireland, two forms of neonatal screening occur. High-risk infants are fed lactose-free/galactose-free formula until the result of their Beutler screening test on day 1. All other infants are fed as per parental preference and are screened on day three to five. While immediate or early implementation of a strict lactose-free diet together with medical interventions will usually address the acute medical complications, long-term complications are common. We reviewed retrospectively and anonymised the clinical outcomes of our CG cohort, derived from our hospital-based database. Patient demographic information, co-morbidities, developmental assessment results, and other relevant health indicators were analysed from birth to 18 years. Out of 217 patients, 95% of subjects were alive at 18 years of age. Common co-morbidities were speech and language difficulty (43.5%) and learning difficulty (25.5%). In this Irish cohort, Friedreich Ataxia is a genetically linked condition for a subgroup of CG individuals (7.9%). Our data demonstrate that while early diagnosis prevents mortality, it does not prevent developmental disorders, underpinning the neuro-developmental nature of CG. High-risk and routine newborn screening for CG have reduced the mortality rate of the disorder, and early medical and dietetic intervention is a success story. However, long-term medical and developmental challenges persist, and an early, proactive multidisciplinary approach may further mitigate the phenotype in CG patients diagnosed on NBS.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140716","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":"Pancrelipase as Adjunctive Therapy in Severe SCOT Deficiency: A Case of a Novel OXCT1 Gene Deletion","authors":"Mo'ath Abu Hamdeh,&nbsp;Lema Jaber,&nbsp;Jamal Abdullah,&nbsp;Anas Manhal,&nbsp;Mahmoud M. Qouqas,&nbsp;Mohammed Aldwaik,&nbsp;Sarah Abu Rmeilah,&nbsp;Mutaz Sultan,&nbsp;Shaher Shweiki,&nbsp;Nadirah Damseh","doi":"10.1002/jmd2.70024","DOIUrl":"https://doi.org/10.1002/jmd2.70024","url":null,"abstract":"<p>Succinyl-CoA: 3-oxoacid CoA transferase (SCOT) deficiency is a rare autosomal recessive disorder caused by biallelic sequence variants in the <i>OXCT1</i> gene. This deficiency disrupts ketone body utilization, resulting in ketone accumulation and ketoacidosis. Clinical manifestations typically include respiratory distress, vomiting, lethargy, and, in severe cases, coma. This case presents the first known instance of severe SCOT deficiency resulting from a novel homozygous four-exon deletion (exons 4–7) in the OXCT1 gene. The proband presented at the age of 3 months with severe metabolic acidosis that was refractory to conventional management. Despite high doses of bicarbonate therapy and cornstarch, he remained dependent on intravenous glucose for weeks. Repeated attempts to discontinue intravenous glucose led to severe acidosis within 12–24 h. The introduction of pancreatic enzyme replacement therapy (Creon) significantly enhanced starch digestion and absorption, stabilizing his metabolic condition and enabling discharge within 3 days. This case highlights the therapeutic potential of combining pancreatic enzyme replacement with cornstarch in infants under 12 months of age, given their limited pancreatic amylase activity. It underscores a potential management strategy for infants with severe forms of inherited metabolic disorders, such as SCOT deficiency and glycogen storage disease type I, where cornstarch is a cornerstone of therapy.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108749","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}