Molecular Genetics and Metabolism Reports最新文献

{"title":"Optimizing clinical outcomes: The journey of twins with CRIM-negative infantile-onset Pompe disease on high-dose enzyme replacement therapy and immunomodulation","authors":"Angie H. Fares ,&nbsp;Ankit K. Desai ,&nbsp;Laura E. Case ,&nbsp;Cassie Sharon ,&nbsp;Amy Klinepeter ,&nbsp;Amelia Kirby ,&nbsp;Matthew T. Lisi ,&nbsp;Rebecca L. Koch ,&nbsp;Priya S. Kishnani","doi":"10.1016/j.ymgmr.2024.101141","DOIUrl":"10.1016/j.ymgmr.2024.101141","url":null,"abstract":"<div><p>Infantile-onset Pompe disease (IOPD) is caused by a deficiency in the enzyme acid alpha-glucosidase (GAA). It is characterized by severe and progressive hypertrophic cardiomyopathy and muscle weakness with death in the first 2 years of life if left untreated. Enzyme replacement therapy (ERT) with alglucosidase-alfa is lifesaving, but its effectiveness is influenced by the patient's cross-reactive immunologic material (CRIM) status, dose of ERT, and the development of high antibody titers, which can reduce the therapy's efficacy. The inability of CRIM-negative IOPD patients to produce native GAA exposes them to a high risk of development of anti-rhGAA IgG antibody titers, leading to treatment failure. We present the case of CRIM-negative dizygotic twins treated with high-dose alglucosidase-alfa (40 mg/kg/week), initiated at 28 days (Twin A) and 44 days (Twin B). Both twins received immune tolerance induction (ITI) with rituximab, methotrexate, and IVIG to mitigate antibody response. Initial evaluations revealed elevated left ventricular mass index (LVMI) and elevated biomarkers (urine glucose tetrasaccharide (Glc₄), creatine kinase (CK), and aspartate aminotransferase (AST)) in both twins. Following treatment, cardiac function and biomarkers normalized within several months, with a slight delay in Twin B compared to Twin A, likely attributed to the later initiation of ERT. Both twins safely tolerated ITI, achieving immune tolerance with low antibody titers. At 28 months, the twins transitioned to avalglucosidase-alfa (40 mg/kg every other week (EOW)), which was well tolerated without an increase in antibody titers. At 39 months, both twins exhibited normal cardiac function, LVMI, and biomarkers. Motor skills continued to improve, though some kinematic concerns persisted. These cases underscore the importance of early, high-dose ERT combined with ITI in managing CRIM-negative IOPD. While transitioning to avalglucosidase-alfa at 40 mg/kg/EOW was beneficial and well-tolerated in our patients, further studies are needed to confirm its long-term efficacy compared to the high-dose weekly 40 mg/kg alglucosidase-alfa.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101141"},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000946/pdfft?md5=9cd264e8af73cca2574ef0de8bc668a6&pid=1-s2.0-S2214426924000946-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233062","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":"Missense variants of FBN2 associated with congenital arachnodactyly in three Chinese families","authors":"Yu Sui,&nbsp;Yongping Lu,&nbsp;Meina Lin,&nbsp;Xinren Chen,&nbsp;Xiang Ni,&nbsp;Huan Li,&nbsp;Miao Jiang","doi":"10.1016/j.ymgmr.2024.101140","DOIUrl":"10.1016/j.ymgmr.2024.101140","url":null,"abstract":"<div><h3>Background</h3><p>Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder caused by pathogenic variants of Fibrillin-2 (<em>FBN2</em>) gene. This study aimed to investigate the variants in three Chinese families with CCA.</p></div><div><h3>Methods</h3><p>Next-generation sequencing analysis and Sanger sequencing of exons 24–35 of <em>FBN2</em> (NM_001999.4) were performed on the three CCA pedigrees. The pathogenicity of the variants was assessed using ACMG criteria and predicted using an in-silico program.</p></div><div><h3>Results</h3><p>A novel heterozygous substitution (NM_001999.4: c.3230G &gt; A; NP_001990.2 p. Cys1077Tyr) was identified in all patients from pedigree A, but not in healthy family members. The variant was found to be pathogenic. Additionally, in pedigree B (NM_001999.4: c.4222G &gt; A; NP_001990.2: p.Asp1408Asn) and C (NM_001999.4: c.3170G &gt; A; NP_001990.2: p.Gly1057Asp), and the previously reported variants were detected. Variants affecting cysteine residues may disrupt disulfide bridging, leading to a weakened microfibril scaffold, resulting in CCA phenotypes. High phenotypic heterogeneity was observed among different families, and there was little correlation between the genotype and phenotype.</p></div><div><h3>Conclusion</h3><p>This study describes three large families with CCA caused by missense variants in the <em>FBN2</em> gene. Phenotypic variations were observed among different pedigree groups, and further research is needed to investigate the underlying reasons for these variations.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101140"},"PeriodicalIF":1.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000934/pdfft?md5=65ae1d4fa45d800bf053f549131f8b0e&pid=1-s2.0-S2214426924000934-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161853","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":"An acute life-threatening episode of rhabdomyolysis, renal failure, altered mental status and hyperammonemia in an adult with 3-methylcrotonyl-CoA carboxylase deficiency","authors":"Rachel McGowan,&nbsp;Shoji Yano","doi":"10.1016/j.ymgmr.2024.101138","DOIUrl":"10.1016/j.ymgmr.2024.101138","url":null,"abstract":"<div><p>3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency is an autosomal recessive disorder of leucine metabolism. Since 3-MCC deficiency is thought to be a benign condition, a few newborn screening programs discontinued to screen this condition. We report a case of a 24-year-old previously healthy male patient who developed generalized rhabdomyolysis, weakness, respiratory and renal failure, acute pancreatitis, hyperammonemia, and altered consciousness after strenuous exercise. Diagnosis of 3-MCC was made based on increased plasma C5OH carnitine, urine 3-methylcrotonylglycine, and 3-hydroxyisovalerate, and later whole genome sequencing study confirmed the diagnosis. Low plasma carnitine and high creatine kinase (CK) levels were again noted after two months of poor compliance with carnitine therapy. Since 3-MCC deficiency is often incidentally diagnosed in asymptomatic mothers through positive newborn screening in the newborns and most positive newborn screening cases have benign clinical outcomes, 3-MCC deficiency has been considered a benign condition. Observation of a life-threatening episode triggered by strenuous exercise and recurrent occurrence of low carnitine and high CK without carnitine supplementation may support 3-MCC deficiency to be the condition covered by the newborn screen since carnitine supplementation likely prevents an episode that can be life-threatening. Asymptomatic adults with 3-MCC deficiency may benefit from periodic evaluation of plasma carnitine levels.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101138"},"PeriodicalIF":1.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000910/pdfft?md5=8ec486bf2809c93573f13aafc0119a1e&pid=1-s2.0-S2214426924000910-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098203","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":"Rapid genotyping of inversion variants in Mucopolysaccharidosis type II using long-range PCR: A case report","authors":"Yusuke Hattori ,&nbsp;Jun Kido ,&nbsp;Keishin Sugawara ,&nbsp;Takaaki Sawada ,&nbsp;Shirou Matsumoto ,&nbsp;Kimitoshi Nakamura","doi":"10.1016/j.ymgmr.2024.101139","DOIUrl":"10.1016/j.ymgmr.2024.101139","url":null,"abstract":"<div><p>Mucopolysaccharidosis II (MPS II) is a lysosomal storage disease caused by a deficiency in iduronate-2-sulfatase (IDS), leading to the accumulation of dermatan sulfate and heparan sulfate in lysosomes. Traditionally, genotyping of the <em>IDS</em> gene has been conducted through exome sequencing, which fails to detect inversion variants. Consequently, when no pathogenic variants are detected in exons, additional PCR-based analysis is required. Herein, we introduce a rapid genotyping technique method using long-range PCR for MPS II patients. We successfully identified an inversion variant and confirmed the sequences of the inversion regions. We also confirmed that the pathogenic variant in the patient originated <em>de novo</em>. These findings suggest that long-range PCR genotyping can identify inversion variants more rapidly compared to the previous PCR-based methods, making it a valuable tool for newborn screening (NBS) and genetic diagnosis.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101139"},"PeriodicalIF":1.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000922/pdfft?md5=bb80a5595957f992b474ea8d2a3ed1a6&pid=1-s2.0-S2214426924000922-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098206","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":"Ataluren-mediated nonsense variant readthrough in D-bifunctional protein deficiency: A case report","authors":"Rai-Hseng Hsu ,&nbsp;Ni-Chung Lee ,&nbsp;Hui-An Chen ,&nbsp;Wuh-Liang Hwu ,&nbsp;Wang-Tso Lee ,&nbsp;Yin-Hsiu Chien","doi":"10.1016/j.ymgmr.2024.101137","DOIUrl":"10.1016/j.ymgmr.2024.101137","url":null,"abstract":"<div><p>D-bifunctional protein (DBP) deficiency, a fatal peroxisomal enzyme disorder, typically manifests with life-threatening symptoms in the first two years of childhood. We present the case of an infant with elevated lysophosphatidylcholine C26:0 (C26:0-LPC) levels identified during X-linked adrenoleukodystrophy (ALD) screening, leading to a diagnosis of DBP deficiency due to a homozygous <em>HSD17B4</em> c.1041T&gt;A, p.(Tyr347Ter) variant. Starting at two months of age, the infant experienced seizures, hypotonia, and developmental delays, prompting the initiation of experimental treatment with the readthrough agent PTC124 (ataluren) at six months. The treatment led to a decrease in C26:0-LPC levels from 0.65 μM to 0.53 μM; concomitant fish oil supplementation transiently increased C26:0-LPC to 0.74 μM before returning to 0.53 μM after cessation of supplementation. The patient demonstrated improved swallowing and progressive motor and speech development during a two-year treatment period, with no further seizures. This case report highlights the potential of nonsense readthrough therapy for peroxisomal disorders, a group of metabolic diseases that currently lack targeted treatments.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101137"},"PeriodicalIF":1.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000909/pdfft?md5=3b87bdeb125a1aee0c39640f61ae6f15&pid=1-s2.0-S2214426924000909-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098205","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":"Intrafamilial phenotypic variability due to a missense pathogenic variant in FBP1 gene","authors":"Setila Dalili ,&nbsp;Nasrin Sedighi Pirsaraei ,&nbsp;Ameneh Sharifi ,&nbsp;Alireza Pouryousef ,&nbsp;Fatemeh Aghaee ,&nbsp;Reza Bayat ,&nbsp;Babak Ghavami ,&nbsp;Bahareh Rabbani ,&nbsp;Nejat Mahdieh","doi":"10.1016/j.ymgmr.2024.101136","DOIUrl":"10.1016/j.ymgmr.2024.101136","url":null,"abstract":"<div><h3>Background</h3><p>FBPase deficiency as an autosomal recessive disorder is due pathogenic variants in the FBP1 gene. It usually presents with hyperlactic acidemia and hypoglycaemia starting from early childhood. Here, genotypes and phenotypes of all reported patients and their distributions are presented. In addition, we present an Iranian family with two affected children presenting with unusual symptoms due to pathogenic variants in the <em>FBP1</em> gene.</p><p>Clinical evaluations and laboratory assessments were performed for the affected members. Whole exome sequencing (WES) was applied in order to find the causal variant. In addition to segregation analysis within the family, variant pathogenicity analyses and predictions were done via bioinformatics tools and according to ACMG guidelines. The genotypes and detailed clinical features were documented for all patients.</p></div><div><h3>Results</h3><p>The study included a population of 104 patients with different variants of the <em>FBP1</em> gene; 75 were homozygotes. The average age of onset was 14.97 months. The most frequent clinical features were metabolic acidosis (71 cases), hypoglycemia (70 cases), vomiting (46 cases), hyperuricemia (37 cases), and respiratory distress (25 cases). 74 families were from Asia. The most common genotypes were c.841G &gt; A/c.841G &gt; A and c.472C &gt; T/c.472C &gt; T. WES test showed a pathogenic homozygous variant, c.472C &gt; T in two cases of a family: a six-and-a-half-year-old girl with an older brother with different symptoms. All laboratory evaluations in the patient were normal except for the blood sugar. The patient experienced her first hypoglycemic episode at age 3.</p></div><div><h3>Conclusions</h3><p>This is an unusual presentation of FBPase deficiency with intrafamilial phenotypic variability.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101136"},"PeriodicalIF":1.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000892/pdfft?md5=40503765e68ec1c2af9b7684c24b3780&pid=1-s2.0-S2214426924000892-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098204","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 broad spectrum of clinical manifestations observed in three patients with L2 hydroxyglutaric aciduria spans from febrile seizures to complex dystonia","authors":"A. Alsayed ,&nbsp;M. Albadrani ,&nbsp;A. Obaid ,&nbsp;A. Alhashim ,&nbsp;A. Alakkas","doi":"10.1016/j.ymgmr.2024.101135","DOIUrl":"10.1016/j.ymgmr.2024.101135","url":null,"abstract":"<div><p>L-2 hydroxyglutaric aciduria (L-2-HGA) is a rare autosomal recessive progressive, organic aciduria which presents with a wide variety of clinical manifestations. Diagnosis is complex and necessitates an increase in clinical suspicion of the disease to obtain the necessary diagnostic tests and thus early administration of appropriate management.</p><p>In this case series, we are reporting three cases of patients with L-2-HGA who presented with a variety of clinical manifestations. All patients presented with a constellation of symptoms including febrile seizures, hyperactivity and intellectual difficulties. One case had an unusual presentation of cervical dystonia in early adulthood. Another case had a homozygous variant, <em>L2HGDH</em>: NM_024884.3: c.368 A &gt; G p. (Tyr123Cys) classified as variant of uncertain significance (VUS) at that time but recently has been reclassified as likely pathogenic variant in clin var. Furthermore, brain MRI of two patients depicted characteristic signs consistent with L-2-HGA. The findings include, symmetrical confluent high T2/FLAIR signal intensity of the white matter involving the subcortical U fibers and deep white matter with sparing of the immediate periventricular white matter, internal capsules and corpus callosum. There was also symmetric abnormal T2 signal intensity of the caudate nuclei, lentiform nucleus as well as the dentate nuclei of the cerebellum.</p><p>Overall, only few cases with similar genetic mutation have been documented in the literature and were of Saudi origin. The aim of the study is to highlight the clinico-radiological features of L-2-HGA to aid in early, prompt diagnosis, and thus appropriate follow up and management of the disease with riboflavin, levocarnitine and a low-lysine diet.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101135"},"PeriodicalIF":1.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000880/pdfft?md5=a48dd86bc822e285d3adf2139d2730f6&pid=1-s2.0-S2214426924000880-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050445","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":"Health economic impact of patients with phenylketonuria (PKU) in France – A nationwide study of health insurance claims data","authors":"Jean-Baptiste Arnoux ,&nbsp;Claire Douillard ,&nbsp;Francois Maillot ,&nbsp;Stéphane Bouée ,&nbsp;Christian Jacob ,&nbsp;Kim Maren Schneider ,&nbsp;Julia Theil ,&nbsp;Sybil Charrière","doi":"10.1016/j.ymgmr.2024.101134","DOIUrl":"10.1016/j.ymgmr.2024.101134","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Phenylketonuria (PKU) is an inherited metabolic disease. If left untreated, it can lead to severe irreversible intellectual disability and can cause seizures, behavior disturbance, and white matter disease. This study aimed at evaluating the health economic impact of patients with PKU in France.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;This retrospective observational study used health insurance claims data from the French SNDS (Système National des Données de Santé) database, which contains data from over 66 million French inhabitants. Patients with PKU were identified by ICD-10 diagnosis codes E70.0 (PKU) and E70.1 (Other hyperphenylalaninemia) documented as a chronic condition (affection de longue durée – ALD) or in the inpatient setting in the SNDS database between 2006 and 2018. Patients with PKU were matched to controls without PKU by age, sex, and region. Patients with early- and late-diagnosed PKU were defined as patients born after and before the implementation of nationwide newborn screening in France in 1972, respectively. Outcomes were analyzed for the year 2018.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Overall, 3549 patients with PKU were identified in the database on January 1st, 2018. Of those, 3158 patients versus 15,703 controls with at least one healthcare consumption in 2018 were available for outcome analyses. Patients with PKU had 7.7 times higher healthcare costs than non-PKU controls in 2018 (€11,144 versus 1456 mean costs; &lt;em&gt;p&lt;/em&gt; &lt; 0.0001). Pharmaceutical costs including dietary amino acid supplements were the cost driver and contributed 80.0% of the overall mean difference (MD) between patients with PKU and matched non-PKU controls. More than half (52.4%) of the mean pharmaceutical costs per patient with PKU was attributable to medical foods including dietary amino acid supplements.&lt;/p&gt;&lt;p&gt;Of the 3158 patients with PKU, 2548 (80.7%) were classified as early-diagnosed and 610 (19.7%) as late-diagnosed. Increased healthcare costs, in comparison to non-PKU controls, were more evident in early-diagnosed patients (€11,263 versus €855 mean costs; 13.2-fold increase; &lt;em&gt;p&lt;/em&gt; &lt; 0.0001). For patients with late-diagnosed PKU, healthcare costs were 2.7-fold higher compared to matched non-PKU controls (€10,644 versus €3951 mean costs; p &lt; 0.0001). Outpatient pharmaceutical costs accounted for 89.1% of the MD between early-diagnosed patients and controls. Among late-diagnosed patients, 55.5% of the MD were attributable to costs for inpatient care, followed by costs for outpatient care (23.9%) and outpatient pharmaceutical costs (20.6%).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;The results indicate that PKU is associated with substantially increased health care costs compared to non-PKU controls in France. The health economic impact was most evident in patients with early-diagnosed PKU due to increased outpatient pharmaceutical costs, especially for medical foods including dietary amino acid supplements. For late-d","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101134"},"PeriodicalIF":1.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000879/pdfft?md5=04b18c64d019bf732131c7a8b2e17138&pid=1-s2.0-S2214426924000879-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012710","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":"Diagnostic challenge of cutis Verticis Gyrata (CVG) in a patient presenting clinical features of Noonan or turner syndrome","authors":"Muskan Kanotra ,&nbsp;Rupinder Kaur ,&nbsp;Chirag Pasricha ,&nbsp;Pratima Kumari ,&nbsp;Ravinder Singh ,&nbsp;Varinder Singh ,&nbsp;Sheikh F. Ahmad","doi":"10.1016/j.ymgmr.2024.101133","DOIUrl":"10.1016/j.ymgmr.2024.101133","url":null,"abstract":"<div><p>Cutis Verticis Gyrata (CVG) is an uncommon condition, often classified as primary (idiopathic) or secondary to other diseases or syndromes. Its pathogenesis remains poorly understood, and its association with genetic syndromes is particularly rare. Noonan and Turner syndromes are distinct genetic disorders with characteristic phenotypes and multiple systemic involvements. This report aims to highlight the diagnostic complexities when CVG presents in the backdrop of these syndromes. A 38 years old patient was presented with chief complaints of receding hairline, dropping eyelids, cerebral deformations with deep furrows and thickened dermis. On the basis of patient's complaints, Noonan or turner syndrome was considered as possible diagnosis. This particular report presents a case of patient suffering from CVG having history of noonan and turner syndrome. With the detailed MRI, histology etc. CVG was finally confirmed. The novelty of this case lies in its rarity, diagnostic complexity, and the need for a multidisciplinary approach to unravel and manage the intersecting conditions. It contributes valuable insights to the existing medical literature, enhancing our understanding of the interplay between dermatological and genetic conditions. Patients with Noonan and turner syndrome exhibit clinical signs and symptoms that are strikingly similar to those of CVG, suggesting that this presents a significant diagnostic problem. An unfavorable outcome could arise from delayed or incorrect diagnosis. Because of this, it is recommended that healthcare fraternities should include uncommon illnesses like CVG as differential diagnosis. Considering CVG in differential diagnosis is crucial for early identification, accurate diagnosis, and comprehensive management. It ensures that associated systemic and genetic conditions are not overlooked and that patients receive holistic and personalized care.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101133"},"PeriodicalIF":1.8,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000867/pdfft?md5=758d177464ee0c23141001840b135b53&pid=1-s2.0-S2214426924000867-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991099","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":"Newborn screening and genetic diagnosis of 3-methylcrotonyl-CoA carboxylase deficiency in Quanzhou,China","authors":"Weihua Lin ,&nbsp;Kunyi Wang ,&nbsp;Yanru Chen ,&nbsp;Zhenzhu Zheng ,&nbsp;Yiming Lin","doi":"10.1016/j.ymgmr.2024.101127","DOIUrl":"10.1016/j.ymgmr.2024.101127","url":null,"abstract":"<div><h3>Background and aims</h3><p>3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD) is an autosomal recessive leucine catabolism condition caused by 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency due to <em>MCCC1</em>/<em>MCCC2</em> variants. We investigated its incidence and features in Quanzhou, China.</p></div><div><h3>Materials and methods</h3><p>We screened 643,606 newborns (January 2014 to December 2022) for elevated 3-hydroxyisovalerylcarnitine (C5OH) levels using tandem mass spectrometry (MS/MS). Molecular analyses identified <em>MCCC1</em>/<em>MCCC2</em> variants in suspected 3-MCCD cases.</p></div><div><h3>Results</h3><p>Seventeen neonates, two maternal patients, and one paternal patient had 3-MCCD. Its incidence in the Quanzhou study population was 1/37,859 newborns. All patients and neonates with 3-MCCD exhibited increased C5OH concentrations. Most patients [76.5%(13/17)] had increased urinary 3-methylcrotonylglycine (3-MCG) and 3-hydroxyisovaleric acid (3-HIVA) levels. Eight neonates and all adults with 3-MCCD had secondary carnitine deficiency. We identified seventeen variants, including 6 novel ones.<em>MCCC1</em>and <em>MCCC2</em> variants were found in 47.1% and 52.9% of patients,with c.1331G &gt; A (31.3%) and c.351_353delTGG (50.0%) being the most prevalent, respectively. Clinical symptoms were observed in 11.8% of patients.</p></div><div><h3>Conclusion</h3><p>We identified six new <em>MCCC1</em>/<em>MCCC2</em> variants, enhancing our understanding of the 3-MCCD molecular profile. Secondary carnitine deficiency occurred in eight neonates and all adult patients. Although clinical symptoms were observed in 11.8% of patients, whether they were related to 3-MCCD remain unclear. Therefore, further studies are required to decide whether 3-MCCD and C5OH indicators should continue to be used.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"40 ","pages":"Article 101127"},"PeriodicalIF":1.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000806/pdfft?md5=e3970176d6cb4d7b8b66d6fcd0a8a509&pid=1-s2.0-S2214426924000806-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933874","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}