Molecular Genetics and Metabolism Reports最新文献

{"title":"Initiation of fluoxetine in a pediatric patient with Mucopolysaccharidosis IIIA: Early observations","authors":"Lindsay Torrice,&nbsp;Elizabeth Jalazo","doi":"10.1016/j.ymgmr.2024.101113","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101113","url":null,"abstract":"<div><p>Fluoxetine has been identified as a potential treatment for mucopolysaccharidosis IIIA (MPS IIIA), a debilitating and progressive lysosomal storage disorder for which no treatments are approved. In the MPS IIIA mouse model, fluoxetine decreases the accumulation of glycosaminoglycans and aggregated autophagic substrates, reducing inflammation, and slowing cognitive deterioration. ¹ We treated a single patient, 6 years old, under off-label prescription of fluoxetine, a selective serotonin reuptake inhibitor (SSRI). The primary endpoint was safety. Secondary exploratory assessments included urine quantitative heparan sulfate. Fluoxetine was well-tolerated in this patient and the patient continued treatment following the 12-month monitoring period. The patient experienced an increase in daytime somnolence which resolved with rescheduling fluoxetine administration to bedtime. Quantitative heparan sulfate levels remained elevated during treatment. Parents reported improved sleep latency time and less nighttime waking. These findings support general tolerability and further study of fluoxetine as a potential therapy for MPS IIIA.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101113"},"PeriodicalIF":1.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000661/pdfft?md5=3a7c10306eebd06f7e9822be11695e94&pid=1-s2.0-S2214426924000661-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of avalglucosidase alfa on forced vital capacity percent predicted in treatment-naïve patients with late-onset Pompe disease: A pooled analysis of clinical trials","authors":"Tahseen Mozaffar ,&nbsp;Lionel Riou França ,&nbsp;Jérôme Msihid ,&nbsp;Pragya Shukla ,&nbsp;Irina Proskorovsky ,&nbsp;Tianyue Zhou ,&nbsp;Magali Periquet ,&nbsp;Kristina An Haack ,&nbsp;Laurence Pollissard ,&nbsp;Volker Straub","doi":"10.1016/j.ymgmr.2024.101109","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101109","url":null,"abstract":"<div><h3>Background</h3><p>The efficacy of avalglucosidase alfa (AVA) versus alglucosidase alfa (ALG) on forced vital capacity percent predicted (FVCpp) in patients with late-onset Pompe disease (LOPD) has been assessed in the Phase 3 COMET trial (<span>NCT02782741</span><svg><path></path></svg>). Due to the rarity of LOPD and thus small sample size in COMET, additional data were analyzed to gain further insights into the efficacy of AVA versus ALG.</p></div><div><h3>Methods</h3><p>Data from treatment-naive patients with LOPD were pooled from COMET and Phase 1/2 NEO1/NEO-EXT (<span>NCT01898364</span><svg><path></path></svg>/<span>NCT02032524</span><svg><path></path></svg>) trials for patients treated with AVA, and Phase 3 LOTS trial (<span>NCT00158600</span><svg><path></path></svg>) for patients treated with ALG. Regression analyses using mixed models with repeated measures consistent with those pre-specified in COMET were performed post-hoc. Analyses were adjusted for trials and differences in baseline characteristics. Four models were developed: Model 1 considered all trials; Model 2 included Phase 3 trials; Model 3 included Phase 3 trials and was adjusted for baseline ventilation use; Model 4 included COMET and NEO1/NEO-EXT (i.e., AVA trials only).</p></div><div><h3>Results</h3><p>Overall, 100 randomized patients from COMET (AVA, <em>n</em> = 51, ALG, <em>n</em> = 49), 60 from LOTS (ALG arm only), and three patients from NEO1/NEO-EXT (who received open-label AVA only) were considered for analysis. Mean age at enrollment was similar across trials (45.3–50.3 years); however, patients from LOTS had a longer mean duration of disease versus COMET and NEO1/NEO-EXT trials (9.0 years and 0.5–2.2 years, respectively) and younger mean age at diagnosis (36.2 years and 44.7–48.6 years, respectively). Least squares mean (95% confidence interval) improvement from baseline in FVCpp at Week 49–52 for AVA versus ALG was 2.43 (−0.13; 4.99) for COMET (<em>n</em> = 98); 2.31 (0.06; 4.57) for Model 1 (<em>n</em> = 160); 2.43 (0.21; 4.65) for Model 2 (<em>n</em> = 157); 2.80 (0.54; 5.05) for Model 3 (<em>n</em> = 154); and 2.27 (−0.30; 4.45) for Model 4 (<em>n</em> = 101).</p></div><div><h3>Conclusions</h3><p>Models 1 to 3, which had an increased sample size versus COMET, demonstrated a nominally significant effect on FVCpp favoring AVA versus ALG after 1 year of treatment, consistent with results from COMET.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101109"},"PeriodicalIF":1.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000624/pdfft?md5=3798cf3b97694ad37072612e447271ae&pid=1-s2.0-S2214426924000624-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and tolerability of givosiran for the management of acute hepatic porphyria: A monocenter real-life evaluation","authors":"Claudio Carmine Guida,&nbsp;Maria Nardella,&nbsp;Aurora del Mar YS Perez,&nbsp;Maria Savino,&nbsp;Gaetano Ferrara,&nbsp;Francesco Napolitano,&nbsp;Annalisa Crisetti,&nbsp;Francesco Aucella,&nbsp;Filippo Aucella","doi":"10.1016/j.ymgmr.2024.101111","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101111","url":null,"abstract":"<div><p>Acute hepatic porphyrias (AHPs) are a family of rare, autosomal, dominantly inherited conditions characterized by abnormalities in the production of heme. Advances in molecular engineering have provided new therapeutic possibilities for modifying the heme synthetic pathway in patients with porphyria. In particular, the RNA interference therapeutic givosiran was approved for the treatment of adults and adolescents with AHP aged &gt;12 years based on the positive results of the phase III trial ENVISION. Despite the extended characterization of the activity of givosiran in clinical trials, reports on the long-term effects and effectiveness of the treatment in clinical practice are still scant. To fill this gap, this case series describes a monocentric Italian cohort of AHP patients treated with givosiran. Overall, our real-life experience supports the clinical evidence that long-term treatment with givosiran is well tolerated and able to provide sustained and continuous benefit to patients with acute intermittent porphyria, as reflected by the reduction in the frequency of attacks. In our series, givosiran treatment was also associated with improvement in assessments of quality of life, pain and fatigue.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101111"},"PeriodicalIF":1.8,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000648/pdfft?md5=6917e40b7a57c9e0d891bb92a83ed97f&pid=1-s2.0-S2214426924000648-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-analytic decrease of phenylalanine in plasma of patients with phenylketonuria treated with pegvaliase","authors":"Coleman Turgeon ,&nbsp;Kari Casas ,&nbsp;Ryan Flanagan ,&nbsp;Amy White ,&nbsp;Dawn Peck ,&nbsp;Gisele Bentz Pino ,&nbsp;April Studinski Jones ,&nbsp;Dimitar Gavrilov ,&nbsp;Devin Oglesbee ,&nbsp;Matthew J. Schultz ,&nbsp;Silvia Tortorelli ,&nbsp;Dietrich Matern ,&nbsp;Patricia L. Hall","doi":"10.1016/j.ymgmr.2024.101110","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101110","url":null,"abstract":"<div><p>Treatment of phenylketonuria (PKU) has evolved since the initial introduction of a phenylalanine (Phe) restricted diet. The most recent option for adults affected with PKU is treatment with an alternate enzyme, phenylalanine ammonia lyase (PAL), that metabolizes excess Phe. Proper management of all patients with PKU relies on accurate measurement of Phe levels in blood, to comply with guidance intended to minimize the neurological symptoms. Recently, our laboratory was notified of discrepant results for a patient with PKU who is treated with pegvaliase. Two specimens were collected at the same time but yielded unexpectedly different Phe concentrations. After exclusion of specimen mix-ups or analytical errors, we suspected that there was residual pegvaliase activity in the specimens continuing to degrade Phe after collection. To investigate this possibility, we performed spiking studies that showed the degradation of Phe over time at ambient temperatures. Sample preparation by protein crash appears to deactivate pegvaliase and prevents further Phe degradation. However, because pegvaliase deactivation would be required immediately following blood collection, appropriate mitigation measures must be implemented, including stringent pre-analytical requirements, alternate sample matrices such as dried blood spots, or point of care testing. Until then, health care professionals need to be cautious in their interpretation of Phe levels in their patients with PKU that are treated with pegvaliase.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101110"},"PeriodicalIF":1.8,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000636/pdfft?md5=03a647c744ba0f3ec53544b7b5a9138b&pid=1-s2.0-S2214426924000636-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded inherited metabolic diseases screening by tandem mass spectrophotometry: The first report from Iran","authors":"Marjan Shakiba ,&nbsp;Mehrdad Yasaei ,&nbsp;Hedyeh Saneifard ,&nbsp;Asieh Mosallanejad ,&nbsp;Mohammad Reza Alaei ,&nbsp;Farzad Kobarfard ,&nbsp;Marjan Esfahanizadeh ,&nbsp;Narges Anousheh","doi":"10.1016/j.ymgmr.2024.101103","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101103","url":null,"abstract":"<div><p>Inherited metabolic diseases (IMD) are a group of rare genetic disorders that can present with a variety of symptoms. Since these disorders are hard to treat once the symptoms occur, neonatal screening may be a logical strategy. Here we evaluate the first results of national expanded IMD screening in Iran. A total of 46 IMDs were screened in this national program. Between April 2018 and March 2022, all infants who underwent national IMD screening at Shahid Beheshti University of Medical Sciences were included in this study. History and Physical examinations of infants, screening results, recall rate, response rate, and prevalence of IMDs were evaluated. A total of 125,819 infants were screened during this period. The recall rate of the test was 0.81%. 124 cases were diagnosed with a definite IMD and the raw overall prevalence of IMDs was estimated to be 1:1015. Aminoacidopathies were the most commonly detected disorders and Hyperphenylalaninemia/PKU was the most prevalent disorder among all groups. Since IMDs vary from region even in a single country, screening for IMDs is crucial in societies with a high rate of consanguineous marriages. More studies are essential for figuring out the most efficient combination of diseases to be screened based on countries' facilities.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101103"},"PeriodicalIF":1.9,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000569/pdfft?md5=c01a2a0ec5f18e7562a58d2bfc5c8b7c&pid=1-s2.0-S2214426924000569-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141429295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial schwannomatosis carrying LZTR1 variant p.R340X with brain tumor: A case report","authors":"Masaki Ibe ,&nbsp;Shinobu Tamura ,&nbsp;Hideki Kosako ,&nbsp;Yusuke Yamashita ,&nbsp;Masamichi Ishii ,&nbsp;Masaoh Tanaka ,&nbsp;Hiroyuki Mishima ,&nbsp;Akira Kinoshita ,&nbsp;Sadahiro Iwabuchi ,&nbsp;Shuhei Morita ,&nbsp;Ko-ichiro Yoshiura ,&nbsp;Shinichi Hashimoto ,&nbsp;Naoyuki Nakao ,&nbsp;Shigeaki Inoue","doi":"10.1016/j.ymgmr.2024.101107","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101107","url":null,"abstract":"<div><p>Schwannomatosis (SWN) is a rare genetic condition characterized by the risk of developing multiple benign peripheral nerve sheath tumors; however, the risk of developing malignant tumors in patients with SWN remains unclear. This study described the case of a 57-year-old Japanese man diagnosed with SWN whose older brother also had SWN. Whole-exome sequencing identified a heterozygous mutation [c.1018C &gt; T (p.Arg340X)] in the <em>LZTR1</em> gene, linked to the RAS/MAPK pathway, in the patient and his brother. Moreover, the patient had aphasia and right-sided paralysis because of a brain tumor. RNA sequencing revealed the remarkable upregulation of several genes associated with oxidative stress, such as the reactive oxygen species pathway and oxidative phosphorylation, a downstream effector of the RAS/MAPK pathway, in the the patient and his brother compared with healthy volunteers. The final diagnosis was <em>LZTR1</em>-related familial SWN, and the dysregulated RAS/MAPK pathway in this patient might be associated with brain tumorigenesis.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101107"},"PeriodicalIF":1.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000600/pdfft?md5=f82983422b5d7b997e3c651235e5fb37&pid=1-s2.0-S2214426924000600-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141423750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term use of investigational β-Hydroxybutyrate salts in children with multiple acyl-CoA dehydrogenase or pyruvate dehydrogenase deficiency","authors":"Andrew A.M. Morris ,&nbsp;Bernard Cuenoud ,&nbsp;Philippe Delerive ,&nbsp;Helen Mundy ,&nbsp;Bernd C. Schwahn","doi":"10.1016/j.ymgmr.2024.101104","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101104","url":null,"abstract":"<div><p>Several disorders of energy metabolism have been treated with exogenous ketone bodies. The benefit of this treatment is best documented in multiple acyl-CoA dehydrogenase deficiency (MADD) (MIM#<span>231680</span><svg><path></path></svg>). One might also expect ketone bodies to help in other disorders with impaired ketogenesis or in conditions that profit from a ketogenic diet. Here, we report the use of a novel preparation of dextro-β-hydroxybutyrate (D-βHB) salts in two cases of MADD and one case of pyruvate dehydrogenase (PDH) deficiency (MIM#<span>312170</span><svg><path></path></svg>). The two patients with MADD had previously been on a racemic mixture of D- and L‑sodium hydroxybutyrate. Patient #1 found D-βHB more palatable, and the change in formulation corrected hypernatraemia in patient #2. The patient with PDH deficiency was on a ketogenic diet but had not previously been given hydroxybutyrate. In this case, the addition of D-βHB improved ketosis. We conclude that NHS101 is a good candidate for further clinical studies in this group of diseases of inborn errors of metabolism.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101104"},"PeriodicalIF":1.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000570/pdfft?md5=3e0c53b41aae64a8fc4f1efb683842e9&pid=1-s2.0-S2214426924000570-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tocilizumab effectively reduces flares of hyperimmunoglobulin D syndrome in children: Three cases in China","authors":"Chenxi Li ,&nbsp;Xiangyuan Chen ,&nbsp;Xilong Tang ,&nbsp;Huasong Zeng ,&nbsp;Juan Zhou","doi":"10.1016/j.ymgmr.2024.101105","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101105","url":null,"abstract":"<div><p>Hyperimmunoglobulin D syndrome (HIDS) is a rare but severe autoinflammatory disease with a poor prognosis if not diagnosed and treated early. Here, we report three cases of HIDS in children with typical clinical manifestations and a clear genetic diagnosis. Patient 1 experienced recurrent fever flares with a maculo-papular skin rash. Patient 2 presented with periodic fever, cholestasis, lymphadenopathy, aphthous stomatitis, arthralgia, and abdominal pain and underwent surgery for intestinal obstruction. Patient 3, a sibling of patient 2, presented with periodic fever and underwent a surgical procedure for intussusception. All three patients were administered interleukin (IL)-6 receptor antagonist (tocilizumab). The results showed that tocilizumab effectively reduced inflammatory flares. Early diagnosis and tocilizumab treatment are effective at improving the prognosis of HIDS patients.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101105"},"PeriodicalIF":1.9,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000582/pdfft?md5=19f62876f2e56f6c493db06a1c7380a0&pid=1-s2.0-S2214426924000582-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histologic and ultrastructural study of intracranial Gaucheroma causing deafness in a patient with Gaucher disease type 3: Effects of substrate reduction therapy","authors":"Shoji Yano ,&nbsp;Rachel McGowan ,&nbsp;Mikako Warren","doi":"10.1016/j.ymgmr.2024.101106","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101106","url":null,"abstract":"<div><p>Hearing loss is frequently associated with Gaucher disease (GD). Gaucher cells are enlarged reticuloendothelial cells containing glucocerebroside in the lysosomes due to deficiency of the glucocerebrosidase. Gaucheromas consist of accumulated Gaucher cells. Gaucher cells accumulate in variable tissues including the liver, spleen, bone marrow, and the middle ear and the mastoid causing conductive hearing loss. Neurons and astrocytes in the central nervous system are affected in neuronopathic GD leading to sensorineural hearing loss. Gaucheromas can develop even in patients treated with enzyme replacement therapy (ERT). We report a 19-year-old female patient with GD type 3 who developed profound bilateral hearing loss associated with intracranial Gaucheroma. Combination therapy of ERT with imiglucerase and substrate reduction therapy (SRT) with eliglustat significantly decreased the size of Gaucher cells and cleared the characteristic microtubular structures in the lysosomes in Gaucher cells. Early implementation of SRT may prevent at least conductive hearing impairment in GD although it may not prevent sensorineural hearing loss due to inner hair cell dysfunction which is also known to be associated with neuronopathic GD.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101106"},"PeriodicalIF":1.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000594/pdfft?md5=8ca89347a9625bde9b1ee36d251bf75e&pid=1-s2.0-S2214426924000594-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141323237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between circulating phenylalanine and the temporal risk of impaired insulin markers in gestational diabetes mellitus","authors":"Hao Wu ,&nbsp;Qiong Wang ,&nbsp;Yanmin Chen ,&nbsp;Danqing Chen","doi":"10.1016/j.ymgmr.2024.101090","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101090","url":null,"abstract":"<div><h3>Background</h3><p>We aimed to contrast plasma amino acid concentrations in pregnant women with Gestational Diabetes Mellitus (GDM) to those without, to analyze the link between plasma amino acid concentrations, GDM, insulin resistance, and insulin secretion at 24–28 weeks of gestation.</p></div><div><h3>Methods</h3><p>The research employed a retrospective case-control study design at a single center. Basic demographic and laboratory data were procured from the hospital's case system. The study encompassed seventy women without gestational diabetes mellitus (GDM) and thirty-five women with GDM matched in a 1-to-2 ratio for age and pre-pregnancy BMI. Utilizing high-performance liquid chromatography-mass spectrometry (HPLC-MS), peripheral fasting plasma amino acid concentrations in these women, during mid-pregnancy, were duly measured. We carefully evaluated the significant differences in the quantitative data between the two groups and developed linear regression models to assess the independent risk factors affecting insulin resistance and insulin secretion.</p></div><div><h3>Results</h3><p>Significant variations in insulin secretion and resistance levels distinguished GDM Group from the non-GDM group at three distinct time points, alongside relatively elevated serum Glycosylated Hemoglobin (HbA1c) levels. Triglycerides (TG) were also significantly increased in those with GDM during adipocytokine observations. Apart from glutamic acid and glutamine, the concentrations of the remaining 16 amino acids were notably increased in GDM patients, including all branched chain amino acids(BCAAs) and aromatic amino acids(AAAs). Ultimately, it was ascertained that fasting serum phenylalanine levels were independent risk factors affecting insulin resistance index and insulin secretion at various phases.</p></div><div><h3>Conclusions</h3><p>Various fasting serum amino acid levels are markedly increased in patients with GDM, specifically phenylalanine, which may play role in insulin resistance and secretion.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101090"},"PeriodicalIF":1.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000430/pdfft?md5=4cf9842462b86f0a63e8f8761bb8f90a&pid=1-s2.0-S2214426924000430-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141323236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}