JIMD reports最新文献_第2页

Irritable Bowel Disease: Think Malonic and Methylmalonic Aciduria (CMAMMA)! 肠易激病：考虑丙二酸和甲基丙二酸尿症（CMAMMA）！

IF 1.8

JIMD reports Pub Date : 2026-08-23 DOI: 10.1002/jmd2.70119

Khaled Alatibi, Martin J. Hug, Sara Tucci

{"title":"Irritable Bowel Disease: Think Malonic and Methylmalonic Aciduria (CMAMMA)!","authors":"Khaled Alatibi, Martin J. Hug, Sara Tucci","doi":"10.1002/jmd2.70119","DOIUrl":"10.1002/jmd2.70119","url":null,"abstract":"Combined malonic and methylmalonic aciduria (CMAMMA; OMIM 614265) is a rare disorder of mitochondrial fatty acid synthesis caused by pathogenic variants in the ACSF3 gene, which encodes malonyl-CoA synthetase. The clinical presentation is highly heterogeneous and may include seizures, memory impairment, psychiatric manifestations, and cognitive decline. We describe an adult patient with long-standing unexplained fatigue and irritable bowel syndrome who remained undiagnosed for 15 years. Subsequent blood and urine analyses revealed elevated methylmalonic acid levels, and molecular genetic testing identified the biallelic ACSF3 variant c.1672C>T (p.Arg558Trp), confirming the diagnosis of CMAMMA. Functional studies in patient-derived fibroblasts demonstrated altered global protein malonylation together with markedly reduced lipoylation of pyruvate dehydrogenase complex and α-ketoglutarate dehydrogenase, consistent with impaired mitochondrial energy metabolism. Introduction of a diet enriched in carbohydrates and restricted in protein, based on recommendations for methylmalonic aciduria, resulted in a pronounced worsening of gastrointestinal symptoms, which improved after discontinuation of the dietary intervention. This case highlights that CMAMMA may remain unrecognized for many years and should also be considered in adults presenting with unexplained gastrointestinal symptoms. Furthermore, the findings suggest that impaired glucose oxidation plays a central role in disease pathophysiology and that high dietary carbohydrate intake may exacerbate clinical manifestations.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808540","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}

引用次数: 0

Hormonal Responses to a Short Daytime Fast in Children With Beta-Oxidation Disorders β -氧化障碍儿童短暂日间禁食的激素反应。

IF 1.8

JIMD reports Pub Date : 2026-08-23 DOI: 10.1002/jmd2.70120

David Olsson, Maria Halldin, Charlotte Bieneck Haglind, Svetlana Lajic, Anna Nordenström

{"title":"Hormonal Responses to a Short Daytime Fast in Children With Beta-Oxidation Disorders","authors":"David Olsson, Maria Halldin, Charlotte Bieneck Haglind, Svetlana Lajic, Anna Nordenström","doi":"10.1002/jmd2.70120","DOIUrl":"10.1002/jmd2.70120","url":null,"abstract":"Fasting-induced cellular energy deficiency and hypoglycemia are well-known complications of beta-oxidation disorders. The changes in energy homeostasis during fasting are under hormonal regulation. This aspect of fasting metabolism in beta-oxidation disorders is not fully characterized. This clinical study investigates hormonal and substrate profiles during fasting and after a standardized meal in patients with beta-oxidation disorders compared with age-matched healthy controls. Children with beta-oxidation disorders (4 LCHADD, 5 VLCADD, 6 MCADD, median age 8.5, 3–13 years) and healthy age-matched controls (n = 12, median age 9.5, 5–13 years) were subjected to a 4-h daytime fast. Blood samples for glucose, ketones, amino acids, nonesterified fatty acids (NEFA), acylcarnitines, and a panel of metabolically active hormones were analyzed after a 4-h fast and 60 min after intake of the standardized meal. Patients with a beta-oxidation disorder displayed a normal glycemic response to fasting. Most hormonal changes were similar to the changes observed in controls. However, children with LCHADD had higher insulin levels and BMI but, interestingly, relatively low HbA1c compared to children with VLCADD and MCADD. Our findings regarding a possible increased risk of insulin resistance in patients with LCHADD need to be verified in larger cohorts.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813186","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}

引用次数: 0

Challenges in Managing Pregnancy in Patients With Fructose 1, 6-Bisphosphatase Deficiency: A Single-Centre Experience 果糖1,6 -双磷酸酶缺乏症患者妊娠管理的挑战：单中心经验

IF 1.8

JIMD reports Pub Date : 2026-08-13 DOI: 10.1002/jmd2.70116

Raashda A. Sulaiman, Ibrahim Alqasir, Dana Alqasabi, Ruqaiah AlTassan, Maha Tulbah, Maha Alnemer, Mohamed Al-Owain

{"title":"Challenges in Managing Pregnancy in Patients With Fructose 1, 6-Bisphosphatase Deficiency: A Single-Centre Experience","authors":"Raashda A. Sulaiman, Ibrahim Alqasir, Dana Alqasabi, Ruqaiah AlTassan, Maha Tulbah, Maha Alnemer, Mohamed Al-Owain","doi":"10.1002/jmd2.70116","DOIUrl":"https://doi.org/10.1002/jmd2.70116","url":null,"abstract":"Fructose-1,6-bisphosphatase deficiency is a rare inherited metabolic disorder of gluconeogenesis characterized by recurrent hypoglycemia and lactic acidosis, typically triggered by inadequate glucose intake or increased consumption of fructose, sucrose, or sorbitol. During pregnancy, the risk of hypoglycemia and lactic acidosis increases because endogenous glucose production is limited while fetal glucose demand rises. Here we report three patients with fructose-1,6-bisphosphatase deficiency who had successful pregnancies and deliveries. These patients were managed by a multidisciplinary team of obstetricians, maternal-fetal medicine specialists, metabolic physicians, and metabolic dieticians. All patients were obese; one had morbid obesity. Two patients developed gestational diabetes mellitus. One responded to dietary intervention, whereas the patient with morbid obesity had poor dietary adherence, suboptimal glycemic control, and experienced an episode of severe life-threatening hypoglycemia with lactic acidosis requiring intensive care. She recovered fully, with no adverse maternal or fetal effects. All patients had normal vaginal deliveries and were closely monitored during labor, delivery, and the postpartum period. Both patients with gestational diabetes developed lactic acidosis immediately after delivery despite stable blood glucose levels. Managing gestational or type 2 diabetes in patients with fructose-1,6-bisphosphatase deficiency is particularly challenging because the disorder predisposes them to hypoglycemia. This case series contributes to the limited literature on pregnancy outcomes and highlights key management challenges in this rare condition.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753293","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}

引用次数: 0

Medium Chain Acyl-CoA Dehydrogenase Deficiency; an Unexpected Cause of Neonatal Ketoacidosis 中链酰基辅酶a脱氢酶缺乏；新生儿酮症酸中毒的意外原因。

IF 1.8

JIMD reports Pub Date : 2026-08-10 DOI: 10.1002/jmd2.70118

Nazreen Kamarus Jaman, Isaac Bernhardt, Sophie Ward, Freya Hassall, James Nurse, Hugh Lemonde, R. Neil Dalton, Michael Champion

{"title":"Medium Chain Acyl-CoA Dehydrogenase Deficiency; an Unexpected Cause of Neonatal Ketoacidosis","authors":"Nazreen Kamarus Jaman, Isaac Bernhardt, Sophie Ward, Freya Hassall, James Nurse, Hugh Lemonde, R. Neil Dalton, Michael Champion","doi":"10.1002/jmd2.70118","DOIUrl":"10.1002/jmd2.70118","url":null,"abstract":"Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) classically presents with hypoketotic hypoglycaemia; however, this presentation is now rare following the introduction of newborn screening. While children with MCADD may produce some ketones, severe ketoacidosis has not been previously described. Here we report two patients with MCADD presenting with severe ketoacidosis in the neonatal period prior to results of newborn screening. Patient 1 presented on Day 5 with hypoglycaemia, profound ketoacidosis and circulatory shock, and developed refractory ventricular tachycardia requiring extra-corporeal membrane oxygenation. Patient 2 presented on Day 4 with severe ketoacidosis, but only borderline hypoglycaemia. The diagnosis of MCADD was rapidly confirmed in both by analysis of acylcarnitines and urine organic acids, with subsequent genetic confirmation of ACADM mutations. We conclude that MCADD should be included in the differential diagnosis of neonatal ketoacidosis, with or without hypoglycaemia.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706663","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}

引用次数: 0

The Impact of Hydrotherapy on Health-Related Quality of Life, Pain and Mobility in Individuals With Mucopolysaccharidosis Type II (Hunter Syndrome): A Pilot Feasibility Study 水疗法对II型粘多糖病（Hunter综合征）患者健康相关生活质量、疼痛和活动能力的影响：一项试点可行性研究

IF 1.8

JIMD reports Pub Date : 2026-08-10 DOI: 10.1002/jmd2.70114

Andrew Oldham, Nicole Stockton, Mark Warburton, Calvin Heal, Marie Meehan, Karolina M. Stepien, the MPS Society

{"title":"The Impact of Hydrotherapy on Health-Related Quality of Life, Pain and Mobility in Individuals With Mucopolysaccharidosis Type II (Hunter Syndrome): A Pilot Feasibility Study","authors":"Andrew Oldham, Nicole Stockton, Mark Warburton, Calvin Heal, Marie Meehan, Karolina M. Stepien, the MPS Society","doi":"10.1002/jmd2.70114","DOIUrl":"10.1002/jmd2.70114","url":null,"abstract":"Enzyme Replacement Therapy (ERT) is the clinical standard for Mucopolysaccharidosis II (MPSII), yet its limited penetration into poorly vascularised tissues such as bone, cartilage and heart valves leaves participants with significant musculoskeletal morbidity. This small study evaluated the feasibility of hydrotherapy as an adjunct to ERT in addressing these therapeutic gaps and improving Health-Related Quality of Life (HRQoL). Using a crossover design, the study assessed five male participants with MPSII. Key outcomes included HRQoL via the Short Form Health Survey (SF-36), functional mobility by the 6-Minute Walk Test (6MWT) and pain interference through the Brief Pain Inventory (BPI). Data from the SF-36 and BPI showed improvements, including a mean improvement in Physical Functioning, Role Physical and Social Functioning and a mean reduction of 16.2 in pain interference. Analgesic relief over 24 h was 45.8% in the hydrotherapy arm, compared to 18% in the observation arm. Psychological conditions including anxiety, depression and kinesiophobia were also analysed. Participants demonstrated a mean increase of 44.5 m in the 6MWT, suggesting that the ‘unloading’ effect of water facilitated gait speed and endurance (compared to observation arm: mean difference 55.8 m 95% CI −51.6 to 163.1). Participants achieved a mean strength increase of 6.1 lb. during the hydrotherapy arm without adverse effects, corroborating the safety of aquatic resistance training in fragile populations. Our findings demonstrate the feasibility of hydrotherapy as an adjunct to ERT in participants with MPSII. By managing pain and improving HRQoL, hydrotherapy addresses physical and psychological burdens that ERT alone cannot achieve.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712612","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}

引用次数: 0

Characterization of Adult Patients With Neurometabolic Disorders: A Cross-Sectional Study at a Tertiary Neurology Center in Sweden 成年神经代谢紊乱患者的特征：瑞典三级神经病学中心的横断面研究

IF 1.8

JIMD reports Pub Date : 2026-08-01 DOI: 10.1002/jmd2.70115

Boel Ernerdahl, Ashraf Yahia, Andreas Puschmann

{"title":"Characterization of Adult Patients With Neurometabolic Disorders: A Cross-Sectional Study at a Tertiary Neurology Center in Sweden","authors":"Boel Ernerdahl, Ashraf Yahia, Andreas Puschmann","doi":"10.1002/jmd2.70115","DOIUrl":"https://doi.org/10.1002/jmd2.70115","url":null,"abstract":"Adult patients with inherited metabolic diseases are often overlooked. Limited data on this population hinder adequate planning of their clinical and social care. In this retrospective, observational, cross-sectional service evaluation study, we reviewed the electronic medical records of adult patients with inherited neurometabolic diseases (NIMD) managed at Skåne University Hospital between 2020 and 2024. Skåne University Hospital, located in Region Skåne in Southern Sweden, is one of three specialized tertiary centers for inherited metabolic diseases in Sweden. The aim of this study was to characterize these patients demographically and clinically and to describe their treatment profiles, functional status, and social support. We identified 59 patients. Most patients had disorders of intermediary energy metabolism (21/59; 35.6%) or lipid metabolism (14/59; 23.7%), including 10 patients (16.9%) with adrenoleukodystrophy. Disease-specific treatments were provided to 65.4% of patients, and 83.6% were under continuous follow-up. Sixteen patients (27.1%) were fully independent, lived in their own homes, did not require societal support nor mobility aid, and worked/studied full time/retired due to old age. More than half of the patients (50.8%) received no disability or social support. In conclusion, adult patients with NIMD represent a heterogeneous group with variable clinical and social needs. Despite the rarity of individual NIMDs, disease-specific treatments were commonly used in our center. Further studies, particularly long-term follow-up studies, are required to better understand NIMD clinical trajectories and to optimize both medical management and social support for adults with NIMD.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647782","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}

引用次数: 0

Early Versus Late Enzyme Replacement Therapy in Siblings With Morquio A Syndrome: Insights Into Therapeutic Timing 兄弟姐妹Morquio A综合征的早期与晚期酶替代治疗：对治疗时间的见解。

IF 1.8

JIMD reports Pub Date : 2026-07-26 DOI: 10.1002/jmd2.70095

Shinjie Choi, Hyoungmin Kim, Tae-Joon Cho, Jung Min Ko

{"title":"Early Versus Late Enzyme Replacement Therapy in Siblings With Morquio A Syndrome: Insights Into Therapeutic Timing","authors":"Shinjie Choi, Hyoungmin Kim, Tae-Joon Cho, Jung Min Ko","doi":"10.1002/jmd2.70095","DOIUrl":"10.1002/jmd2.70095","url":null,"abstract":"Enzyme replacement therapy (ERT) with elosulfase alfa is the only approved treatment for mucopolysaccharidosis type IVA. This case report delineates the 5-year outcomes of ERT in two Korean siblings with mucopolysaccharidosis type IVA, with the younger sibling initiating treatment at 0.8 years of age and the older one at 5.4 years. Both patients exhibited a progressive decline in their height standard deviation scores, with trajectories paralleling the natural history curves of the disease. At 5.2 years of age, persistent skeletal dysplasia was evident in both siblings. However, the younger sibling demonstrated attenuated disease severity, lacking cervical myelopathy or spinal stenosis requiring C1 laminoplasty. Cardiorespiratory assessment revealed normalized left ventricular mass index z-scores, stable ejection fractions, and the absence of valvular pathology. Overall, these findings suggest that early ERT attenuates severe spinal and upper body manifestations but does not prevent lower limb skeletal progression, highlighting the need for early therapeutic initiation along with orthopedic intervention to preserve cardiorespiratory parameters and functional independence.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591775","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}

引用次数: 0

Neonatal Acute Liver Failure due to Citrin Deficiency (NALFCD) 新生儿柠檬酸缺乏症引起的急性肝衰竭（NALFCD）。

IF 1.8

JIMD reports Pub Date : 2026-07-22 DOI: 10.1002/jmd2.70110

Hoi-Yin Chan, Rosanna Wong, Cheuk-Wing Fung, Kiran Moti Belaramani, Chloe Miu Mak, Matthew Yeung, Toby Chan, Carmen Yeung, Yvonne Kwok, Anne Mei-Kwun Kwok

{"title":"Neonatal Acute Liver Failure due to Citrin Deficiency (NALFCD)","authors":"Hoi-Yin Chan, Rosanna Wong, Cheuk-Wing Fung, Kiran Moti Belaramani, Chloe Miu Mak, Matthew Yeung, Toby Chan, Carmen Yeung, Yvonne Kwok, Anne Mei-Kwun Kwok","doi":"10.1002/jmd2.70110","DOIUrl":"10.1002/jmd2.70110","url":null,"abstract":"Both citrin deficiency (CD) and citrullinemia type I (CTLN1) may be detected by elevated citrulline through newborn screening (NBS) or present as acute liver failure in later infancy, but they differ significantly in management. This may pose therapeutic challenges in the early period after presentation while awaiting diagnostic confirmation. We report a Chinese girl (birth weight 1.98 kg at 37 weeks) who was recalled on day 5 for elevated citrulline (47 μmol/L; cutoff < 25) and citrulline/arginine ratio of 7.34 at NBS on day 2. Citrulline rose to 264 μmol/L upon retesting on day 5. Initial investigations revealed INR of 3.4 and raised alkaline phosphatase, while ammonia, conjugated bilirubin, glucose, albumin, gamma-glutamyl transferase, and transaminases were normal. Suspected CTLN1 led to halting protein intake and starting high glucose infusion. Within 17 h, INR increased to 6.5 and albumin dropped. Worsening hepatic function following high-glucose intake and her small for gestation age status suggested CD. She improved rapidly after switching to lactose-free MCT-enriched formula. Genetic analysis revealed compound heterozygous known pathogenic mutations in the SLC25A13 gene, confirming the diagnosis of CD. This is the first report of CD presenting with neonatal acute liver failure without cholestasis. It highlights the importance of prompt differentiation between CD and CTLN1 in NBS recalls for safe and effective interim treatment.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578316","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}

引用次数: 0

Thoracic Aortic Dissection in a Patient With Classical Homocystinuria: Implications for Aortic Surveillance 经典同型半胱氨酸尿患者的胸主动脉夹层：主动脉监测的意义。

IF 1.8

JIMD reports Pub Date : 2026-07-19 DOI: 10.1002/jmd2.70107

Marisa Chard, Jasmin Simi Zhang, Lesley Turner

{"title":"Thoracic Aortic Dissection in a Patient With Classical Homocystinuria: Implications for Aortic Surveillance","authors":"Marisa Chard, Jasmin Simi Zhang, Lesley Turner","doi":"10.1002/jmd2.70107","DOIUrl":"10.1002/jmd2.70107","url":null,"abstract":"Classical homocystinuria (OMIM #236300), a rare inherited metabolic disorder caused by cystathionine beta-synthase (CBS) deficiency, is characterized by markedly elevated homocysteine levels and associated multisystem complications. While the role of homocystinuria in venous thromboembolism is well recognized, there is limited evidence of impact on aortic pathology. We report the first known case of thoracic aortic dissection in a patient with poorly controlled classical homocystinuria. The patient, a 29-year-old female, was diagnosed in childhood after presenting with Marfanoid features and neurodevelopmental issues, and had persistently elevated homocysteine levels. She had morbid obesity (BMI: 52.7 kg/m2) with no known hypertension or aortic disease. She died suddenly from a ruptured thoracic aortic dissection. Post-mortem whole exome sequencing confirmed homozygosity for a pathogenic CBS mutation NM_000071.2: c.1058C>T; p.(Thr353Met) without any additional variants implicated in monogenic aortopathy or aortic dissection. Notably, her younger brother also has classical homocystinuria but no evidence of aortic dilation to date. This case adds to emerging evidence that elevated homocysteine may contribute to structural vascular damage. Our findings underscore the need to consider aortic surveillance in patients with classical homocystinuria, particularly those with inadequate metabolic control or additional risk factors such as obesity, and highlight the importance of early, sustained treatment to mitigate potential vascular risk.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603240","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}

引用次数: 0

Are Functional Brain Networks Sensitive to High Phenylalanine in Adults With Phenylketonuria? 苯丙酮尿症患者脑功能网络对高苯丙氨酸敏感吗？

IF 1.8

JIMD reports Pub Date : 2026-07-03 DOI: 10.1002/jmd2.70108

Vanessa Vallesi, Yosuke Morishima, Laura Winiger, Roman Trepp, Regula Everts, Raphaela Muri

{"title":"Are Functional Brain Networks Sensitive to High Phenylalanine in Adults With Phenylketonuria?","authors":"Vanessa Vallesi, Yosuke Morishima, Laura Winiger, Roman Trepp, Regula Everts, Raphaela Muri","doi":"10.1002/jmd2.70108","DOIUrl":"10.1002/jmd2.70108","url":null,"abstract":"In early-treated adults with phenylketonuria (PKU), the effects of elevated phenylalanine (Phe) on functional brain networks remain poorly understood. While subacute structural brain changes have been reported, their functional significance remains unclear. Executive and attentional functions have been shown to be particularly sensitive to metabolic control in PKU. In this double-blind, randomized, placebo-controlled crossover trial, we investigated the effects of a 4-week high-Phe period on resting-state functional connectivity using seed-based analyses of the dorsal attention and frontoparietal networks, which are critically involved in executive and attentional functions. Twenty-three adults with PKU (median age 35.3 years [IQR 12.0]; 43% female) were included. When baseline connectivity was considered, no significant differences in functional connectivity were observed between the Phe and placebo periods. Without baseline adjustment, exploratory analyses revealed increased functional connectivity of the right frontal eye field within the dorsal attention network with frontal regions. Changes in functional connectivity were neither associated with changes in metabolite concentrations nor in working memory, attention, or executive function. These findings suggest that subacute increases in Phe may induce subtle and potentially transient changes in functional brain networks, although their functional relevance and persistence over longer exposure periods remain unclear.","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381112","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}

引用次数: 0