JIMD reports最新文献

{"title":"Severe neonatal hypotonia due to SLC30A5 variant affecting function of ZnT5 zinc transporter","authors":"Vadim Dolgin,&nbsp;Pauline Chabosseau,&nbsp;Jacob Bistritzer,&nbsp;Iris Noyman,&nbsp;Orna Staretz-Chacham,&nbsp;Ohad Wormser,&nbsp;Noam Hadar,&nbsp;Marina Eskin-Schwartz,&nbsp;Bibi Kanengisser-Pines,&nbsp;Ginat Narkis,&nbsp;Ramy Abramsky,&nbsp;Eilon Shany,&nbsp;Guy A. Rutter,&nbsp;Kyla Marks,&nbsp;Ohad S. Birk","doi":"10.1002/jmd2.12465","DOIUrl":"10.1002/jmd2.12465","url":null,"abstract":"<p>The tightly-regulated spatial and temporal distribution of zinc ion concentrations within cellular compartments is controlled by two groups of Zn²⁺ transporters: the 14-member ZIP/SLC39 family, facilitating Zn²⁺ influx into the cytoplasm from the extracellular space or intracellular organelles; and the 10-member ZnT/SLC30 family, mobilizing Zn²⁺ in the opposite direction. Genetic aberrations in most zinc transporters cause human syndromes. Notably, previous studies demonstrated osteopenia and male-specific cardiac death in mice lacking the ZnT5/<i>SLC30A5</i> zinc transporter, and suggested association of two homozygous frameshift <i>SLC30A5</i> variants with perinatal mortality in humans, due to hydrops fetalis and hypertrophic cardiomyopathy. We set out to decipher the molecular basis of a severe hypotonia syndrome. Combining homozygosity mapping and exome sequencing studies of consanguineous Bedouin kindred, as well as transfection experiments and zinc monitoring in HEK293 cells, we demonstrate that a bi-allelic in-frame 3bp deletion variant in <i>SLC30A5</i>, deleting isoleucine within the highly conserved cation efflux domain of the encoded ZnT5, results in lower cytosolic zinc concentrations, causing a syndrome of severe non-progressive neonatal axial and limb hypotonia with high-arched palate and respiratory failure. There was no evidence of hydrops fetalis, cardiomyopathy or multi-organ involvement. Affected infants required nasogastric tube or gastrostomy feeding, suffered from various degrees of respiratory compromise and failure to thrive and died in infancy. Thus, a biallelic variant in <i>SLC30A5</i> (ZnT5), affecting cytosolic zinc concentrations, causes a severe hypotonia syndrome with respiratory insufficiency and failure to thrive, lethal by 1 year of age.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949104","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":"Liver Transplant From a Deceased Donor With Cystinosis: A Case Report","authors":"Raeda Taj,&nbsp;Kim Ng,&nbsp;Sanmati R. Cuddapah,&nbsp;Elizabeth B. Rand,&nbsp;Melissa Bleicher,&nbsp;Sandra Amaral,&nbsp;Maarouf A. Hoteit,&nbsp;Rajendar K. Reddy,&nbsp;Eyob Feyssa,&nbsp;Emma E. Furth,&nbsp;Kim M. Olthoff,&nbsp;Samir Abu-Gazala,&nbsp;Matthew H. Levine,&nbsp;Frederick Vyas,&nbsp;Peter L. Abt","doi":"10.1002/jmd2.12467","DOIUrl":"10.1002/jmd2.12467","url":null,"abstract":"<p>Many inherited metabolic disorders (IMD) are associated with end-organ damage necessitating organ transplantation. Although utilization of deceased donors with history of IMD warrants caution, there may be circumstances under which such donors could be considered as suitable organ donor candidates. We present the first known report of liver transplantation from a deceased donor with cystinosis. The donor was a 20-year-old male with infantile cystinosis who had previously undergone two deceased donor kidney transplants. Unfortunately, he incurred cranial trauma, and after careful consideration of the metabolic consequences, his liver was deemed suitable for transplantation. The liver was successfully transplanted into a 65-year-old female recipient with hepatitis C (HCV) cirrhosis. The recipient is currently 12 months post-transplant and experiencing good graft function without evidence of cystine crystals on liver biopsy. This case highlights that liver transplantation from donors with rare IMD can result in favorable outcomes. However, it is crucial to approach the use of such livers with caution. These transplants should be considered after a thorough assessment, ensuring that a comprehensive decision-making process is in place to mitigate potential risks.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970827","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":"Development of the Dutch translational knowledge agenda for inherited metabolic diseases","authors":"I. J. Hieltjes,&nbsp;J. H. van der Lee,&nbsp;M. C. Groenendijk,&nbsp;G. van Haaften,&nbsp;P. M. van Hasselt,&nbsp;R. J. Lunsing,&nbsp;G. J. J. van Prooijen,&nbsp;E. M. de Ruiter,&nbsp;F. J. van Spronsen,&nbsp;N. M. Verhoeven-Duif,&nbsp;A. de Vreugd,&nbsp;M. Wagenmakers,&nbsp;H. Zweers,&nbsp;H. Dekker,&nbsp;H. R. Waterham,&nbsp;C. D. van Karnebeek,&nbsp;R. J. A. Wanders,&nbsp;R. A. Wevers","doi":"10.1002/jmd2.12455","DOIUrl":"10.1002/jmd2.12455","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inherited metabolic diseases (IMDs) may have considerable implications for patients and their families. Despite their individual rarity, covering a spectrum of over 1800 distinct diseases, the diseases collectively exert a significant impact, with often lifelong disabilities. The United for Metabolic Diseases consortium was established to catalyze research with translation into the best possible care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To generate a translational knowledge agenda, which identifies and prioritizes research questions, directly relevant to patient care or for IMD patients and their families.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Following a process established by the Knowledge Institute of the Dutch Association of Medical Specialists, we generated a comprehensive translational knowledge agenda for IMDs. A multidisciplinary steering committee, composed of 12 diverse metabolic experts collected research questions through an online questionnaire using snowballing. The 462 proposed questions were categorized and prioritized during a meeting attended by 22 representatives of all stakeholder groups. The resulting top 10 research questions cover multiple themes, i.e. prediction of disease progression, development of novel tools, mechanistic insights, improved diagnostics, therapeutic integration of multi-omics techniques, assessment of impact on daily life, expanding treatment avenues, optimal study designs, effect of lifestyle interventions, and data utilization using FAIR principles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>This collective endeavor reflects the collaborative spirit needed for rare disease research. This knowledge agenda will guide funding directions and applications but will also boost interdisciplinary collaboration to push the field of IMDs research forward in a renewed UMD consortium. Patient engagement, transparency, and a comprehensive approach make this knowledge agenda a pivotal step toward addressing the pressing research needs and priorities in this domain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894563","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 trifunctional protein deficiency caused by a deep intronic deletion leading to aberrant splicing","authors":"Thomas Cassini,&nbsp;Sarah Silverstein,&nbsp;Molly Behan,&nbsp;Cynthia J. Tifft,&nbsp;May Christine Malicdan,&nbsp;David R. Adams,&nbsp;Undiagnosed Diseases Network,&nbsp;Sun-Young Ahn,&nbsp;Debra S. Regier","doi":"10.1002/jmd2.12459","DOIUrl":"https://doi.org/10.1002/jmd2.12459","url":null,"abstract":"<p>Trifunctional protein deficiency (TFP) is a disorder of fatty acid beta-oxidation associated with metabolic, cardiac, and liver dysfunction in severe forms. We present two siblings diagnosed by newborn screening and confirmed by biochemical testing at birth. Their clinical course was complicated by recurrent rhabdomyolysis, retinopathy, and hypoparathyroidism. Both siblings were also diagnosed with focal segmental glomerulosclerosis (FSGS) and bone marrow failure and ultimately died of hypoxemic respiratory failure. Initial sequencing of the TFP-associated genes <i>HADHA</i> and <i>HADHB</i> showed only a paternally inherited variant in <i>HADHB,</i> NM_000183.3:c.1059del (p.Gly354AspfsTer10). Subsequent evaluation by the Undiagnosed Diseases Network with genome and transcriptome sequencing revealed a rare maternally inherited 17 base pair deletion in <i>HADHB</i>, NM_000183.3:c.1390-515_1390-499del, located in the final intron and resulting in a pseudoexon that harbors a premature termination codon. Both sisters were compound heterozygous for this and the paternal premature termination codon. No other variants were detected that were potentially causative for the FSGS and bone marrow failure on genome sequencing. A review of the literature at that time revealed several case reports of the uncommon clinical findings of FSGS, bone marrow failure, and pulmonary involvement in patients with TFP, confirming this clinical diagnosis as the complete explanation for these siblings.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861426","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":"Sleep quality in children with hepatic glycogen storage diseases, a prospective observational pilot study","authors":"Lucas Agnoletto,&nbsp;Moya Vandeleur,&nbsp;Mary White,&nbsp;Anne-Marie Adams,&nbsp;Rebecca Halligan,&nbsp;Heidi Peters","doi":"10.1002/jmd2.12462","DOIUrl":"https://doi.org/10.1002/jmd2.12462","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatic glycogen storage diseases (GSDs) are characterised by enzyme defects affecting liver glycogen metabolism, where carbohydrate supplementation to prevent overnight hypoglycaemia is common. Concerns around sleep quality in hepatic GSDs relate to emerging evidence that overnight dysglycaemia impacts sleep quality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective observational study reported sleep quality and duration in children with hepatic GSDs over 7 days utilising: actigraphy (Actiwatch 2 by Phillips Respironics), sleep diaries, proxy reported age-appropriate sleep and quality-of-life (QoL) questionnaires, in the context of nocturnal glycaemic profiles continuous glucose monitor (CGM, Dexcom G6) and nocturnal dietary management strategies. Significant hypo- and hyperglycaemia were defined as ≥1% of sleep diary documented nocturnal period, recording &lt;3.5 and &gt;10.0 mmol/L, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven children with hepatic GSD (aged 1–17 years) participated. Objective sleep quality was poor, with actigraphy demonstrating that no child achieved the minimum sleep duration recommended for age. Subjective sleep quality was also poor, with 4/5 documenting significant daytime sleepiness and 6/6 reporting poor sleep hygiene. Children prescribed overnight bolus feeds (OBF) (<i>n</i> = 2) recorded shorter sleep duration compared to other nocturnal management strategies. Parent-reported QoL suggested poor disease-related QoL outcomes for this cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Objective and subjective sleep disturbances and reduced QoL are common within our sample of children with hepatic GSD. From our observations these outcomes may be linked to nutritional overnight interventions, especially OBFs, rather than overnight glucose levels. Consideration of the impacts of overnight feeding strategies on sleep quality and QoL in children with hepatic GSD should inform future management strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860674","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":"Acute metabolic decompensation after liver transplant in a patient with maple syrup urine disease","authors":"Shao Ching Tu,&nbsp;Marium Khan,&nbsp;Katie Wolfe,&nbsp;Sakil S. Kulkarni,&nbsp;Elizabeth Toolan,&nbsp;Dorothy K. Grange","doi":"10.1002/jmd2.12460","DOIUrl":"https://doi.org/10.1002/jmd2.12460","url":null,"abstract":"<p>Maple syrup urine disease (MSUD) is an inborn error of metabolism characterized by the accumulation of branched-chain amino acids (leucine, isoleucine, and valine) caused by a defect in the branched-chain alpha-keto acid dehydrogenase complex. Liver transplant is an effective therapy for MSUD, and patients can usually tolerate a regular diet after transplant without symptomatic metabolic decompensation. Most post-transplant patients do not follow a sick-day diet. We report a case of a 7-year-old male with MSUD Type IA, status post-liver transplant at 2 years of age, who presented with profound encephalopathy following poor oral intake and vomiting for 3 days. Broad laboratory workup was significant for hyperleucinosis and an unrevealing infectious workup. We conducted a review of eight post-liver transplant MSUD patients followed at Washington University in St. Louis. The review revealed that plasma amino acids were generally not checked during intercurrent illnesses in this patient cohort. While most of our patients have not had documented encephalopathy, one of the patients with epilepsy had a seizure during a gastrointestinal illness. Based on the review of the literature and from our center's experience, acute metabolic decompensation with intercurrent illnesses in MSUD patients after liver transplant appears to be rare. This case report raises awareness that patients with MSUD are still at risk of developing metabolic crisis post-liver transplant and provides additional insight into the risk factors associated with metabolic decompensation in this patient cohort.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862008","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":"Factors associated with poor outcomes in patients with maple syrup urine disease in a tertiary government hospital: A retrospective cohort study","authors":"Christine Mae S. Avila,&nbsp;Mary Ann R. Abacan","doi":"10.1002/jmd2.12458","DOIUrl":"https://doi.org/10.1002/jmd2.12458","url":null,"abstract":"<p>This study aims to determine the factors associated with mortality and neurodevelopmental morbidity in patients with Maple Syrup Urine Disease (MSUD) seen at a tertiary hospital in the Philippines during a 10-year period. The medical records of patients diagnosed with MSUD seen at Philippine General Hospital (PGH) from 2010 to 2019 were reviewed. Socioeconomic, healthcare, and clinical factors were determined. The association of these factors with mortality and neurodevelopmental morbidity (developmental delay and seizures) was evaluated through statistical analysis. Seventy-five records of MUSD cases were available for review. Fifty-five percent of patients had developmental delay and 57% had seizures. Mortality rate was 25%. Age at collection of newborn screening (OR 1.29, 95% CI 1.04–1.60, <i>p</i> = 0.022) and the number of metabolic crisis in a year (OR 5.4, 95% CI 1.5–19.0, <i>p</i> = 0.008) were significantly associated with increased mortality. Male sex (OR 2.78, 95% CI 1.06–7.26, <i>p</i> = 0.037) and dietary non-compliance (OR 2.56, 95% CI 1.48–4.42, <i>p</i> = 0.001) were associated with increased developmental delay. Age above 5 years (OR 6.5, 95% CI 1.15–36.57, <i>p</i> = 0.034) and nosocomial infections (OR 6.96, 95% CI 1.33–36.53, <i>p</i> = 0.022) were associated with occurrence of seizures. In conclusion, among our cohort of MSUD patients, the age at collection of newborn screening and the number of metabolic crises annually were associated with increased mortality. Male sex, dietary non-compliance, and nosocomial infections were associated with increased neurodevelopmental morbidity.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861349","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, biochemical and molecular characteristics of classic homocystinuria in Saudi Arabia and the impact of newborn screening on prevention of the complications: A tertiary center experience","authors":"Ahmed Sarar Mohamed,&nbsp;Talal AlAnzi,&nbsp;Amal Alhashem,&nbsp;Hadeel Alrukban,&nbsp;Fahad Al Harbi,&nbsp;Sarar Mohamed","doi":"10.1002/jmd2.12454","DOIUrl":"https://doi.org/10.1002/jmd2.12454","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Classic homocystinuria (HCU) is a rare inborn metabolic disease that is generally asymptomatic at birth. If untreated, it can cause a wide range of complications including intellectual disability, lens dislocation, and thromboembolism. This study aimed to describe the natural history and the molecular findings of patients with HCU, and to assess the importance of early diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study retrospectively collected data on patients attending the metabolic unit at Prince Sultan Military Medical City, Riyadh, Saudi Arabia from 2011 to 2024. Demographic, clinical, and molecular data was extracted from the electronic medical records.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 33 patients with HCU enrolled, 5/33 (15%) were diagnosed by newborn screening and the rest were diagnosed on clinical grounds. The complication profile was vast, with neuropsychiatric, musculoskeletal, ophthalmic, and thromboembolic morbidities complicating the disease course in 28/33 (85%) of the patients. None of the newborn screened patients had complications while all of the non-newborn screened patients had at least one complication, <i>p</i> &lt; 0.0001. The majority of parents in this cohort were highly consanguineous, with 90% had first or second cousin marriage. Seven previously reported variants were detected in this cohort and one novel variant was found in three patients (c.828+2-828+ 3 delins ACACTTGCATCC, p.?). The known pathogenic variant (c.969G&gt;A, p. (Trp323*)) was seen in most of the patients, with all of them coming from one tribe.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This cohort gives further evidence that the newborn screening for HCU is likely to prevent the complications associated with the disease at least in the first few years of life. Therefore, newborn screening for HCU should be encouraged. Our molecular studies revealed the presence of a founder variant, detected in patients from a single tribe. This suggests that specific mutation testing may be cost-effective for individuals from certain ethnicities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860776","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":"Disease burden among patients with Arginase 1 deficiency and their caregivers: A multinational, cross-sectional survey","authors":"Sara Olofsson,&nbsp;Sofia Löfvendahl,&nbsp;Julia Widén,&nbsp;Lena Jacobson,&nbsp;Peter Lindgren,&nbsp;Karolina M. Stepien,&nbsp;Jean-Baptiste Arnoux,&nbsp;Maria Luz Couce Pico,&nbsp;Elisa Leão Teles,&nbsp;Mattias Rudebeck","doi":"10.1002/jmd2.12456","DOIUrl":"10.1002/jmd2.12456","url":null,"abstract":"<p>Arginase 1 deficiency (ARG1-D) is an ultrarare, metabolic disease which may cause spastic paraplegia, cognitive deficiency, seizures, and ultimately severe disability. The aim of this study was to assess disease burden in ARG1-D by performing a cross-sectional survey of patients with ARG1-D and their caregivers in four European countries (France, Portugal, Spain, and the United Kingdom). Patients were enrolled at participating clinics and data were collected using a web-based questionnaire. The findings indicate that there is a significant share of patients who experience severe cognitive and mobility impairment but also that there is a considerable variance in symptom severity among patients. Disease management was mostly in line with treatment guidelines and self-reported adherence to treatment was reported to be high among a majority although following diet restrictions was perceived as difficult. However, despite this, since a large share of patients experienced severe cognitive and mobility impairment an unmet need among this patient population is suggested. The introduction of disease-modifying therapies and early identification and diagnosis may help alleviate the disease burden associated with ARG1-D in the future.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"450-460"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604970","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 management of a successful pregnancy and postpartum complications in fructose-1,6-bisphosphatase deficiency","authors":"Callie Ferguson,&nbsp;Anita Madison,&nbsp;Ada Hamosh,&nbsp;Celide Koerner","doi":"10.1002/jmd2.12453","DOIUrl":"10.1002/jmd2.12453","url":null,"abstract":"<p>Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare, inborn error of metabolism, that causes hypoglycemia and lactic acidosis in response to inadequate glucose intake and/or high intakes of fructose, sucrose, or sorbitol. Pregnancy in women with FBPase deficiency puts them at high risk for metabolic decompensation due to increased glucose demands from the growing fetus. Here we report a 31-year-old primipara who was treated starting at 14 weeks gestation with a diet high in complex carbohydrates and low in fructose, sucrose, and sorbitol and close monitoring of glucose levels throughout her pregnancy. She delivered a healthy 2860 g baby at 37 weeks via vaginal delivery with no complications or hypoglycemia. At 5 months postpartum and 5 months of life, the patient and baby are doing well, although the patient experienced an episode of hypoglycemia and lactic acidosis at 4 months postpartum due to the increased metabolic demands of breastfeeding. This report adds to the limited case reports that discuss outcomes and proposed interventions during pregnancy in individuals with FBPase deficiency.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"401-405"},"PeriodicalIF":0.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604990","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}