Pub Date : 2024-08-29DOI: 10.1016/j.ymgmr.2024.101136
Background
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 FBP1 gene.
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.
Results
The study included a population of 104 patients with different variants of the FBP1 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 > A/c.841G > A and c.472C > T/c.472C > T. WES test showed a pathogenic homozygous variant, c.472C > 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.
Conclusions
This is an unusual presentation of FBPase deficiency with intrafamilial phenotypic variability.
{"title":"Intrafamilial phenotypic variability due to a missense pathogenic variant in FBP1 gene","authors":"","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 > A/c.841G > A and c.472C > T/c.472C > T. WES test showed a pathogenic homozygous variant, c.472C > 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":null,"pages":null},"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}
Pub Date : 2024-08-24DOI: 10.1016/j.ymgmr.2024.101135
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.
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, L2HGDH: NM_024884.3: c.368 A > 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.
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.
{"title":"The broad spectrum of clinical manifestations observed in three patients with L2 hydroxyglutaric aciduria spans from febrile seizures to complex dystonia","authors":"","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 > 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":null,"pages":null},"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}
Pub Date : 2024-08-20DOI: 10.1016/j.ymgmr.2024.101134
Background
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.
Methods
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.
Results
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; p < 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.
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; p < 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 < 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%).
Conclusion
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
背景苯丙酮尿症（PKU）是一种遗传性代谢疾病。如果不及时治疗，可导致严重的不可逆转的智力障碍，并可引起癫痫发作、行为紊乱和白质病变。这项回顾性观察研究使用了法国 SNDS（Système National des Données de Santé）数据库中的医疗保险理赔数据，该数据库包含 6600 多万法国居民的数据。2006年至2018年期间，PKU患者在SNDS数据库中被记录为慢性病（Affection de longue durée - ALD）或住院病人，其ICD-10诊断代码为E70.0（PKU）和E70.1（其他高苯丙氨酸血症）。按年龄、性别和地区将PKU患者与未患PKU的对照组进行配对。早期和晚期确诊的PKU患者分别指1972年法国在全国范围内实施新生儿筛查之后和之前出生的患者。对2018年的结果进行了分析。结果总体而言，2018年1月1日，数据库中确认了3549名PKU患者。其中，3158名患者与15703名对照组患者在2018年至少有一次医疗消费，可用于结果分析。2018年，PKU患者的医疗费用是非PKU对照组的7.7倍（平均费用为11144欧元对1456欧元；p <0.0001）。包括膳食氨基酸补充剂在内的医药成本是成本驱动因素，占PKU患者与匹配的非PKU对照组之间总体平均差异（MD）的80.0%。在3158名PKU患者中，2548人（80.7%）被归类为早期诊断，610人（19.7%）被归类为晚期诊断。与非PKU对照组相比，早期诊断患者的医疗费用增加更为明显（平均费用为11263欧元对855欧元；增加13.2倍；p <0.0001）。对于晚期确诊的 PKU 患者，医疗费用比匹配的非 PKU 对照组高出 2.7 倍（平均费用为 10,644 欧元对 3951 欧元；p < 0.0001）。门诊医药费用占早期诊断患者与对照组之间 MD 的 89.1%。在晚期确诊患者中，55.5%的医疗费用来自住院治疗费用，其次是门诊治疗费用（23.9%）和门诊药品费用（20.6%）。由于门诊医药费用的增加，尤其是包括膳食氨基酸补充剂在内的医疗食品费用的增加，对早期诊断的PKU患者的医疗经济影响最为明显。对于确诊较晚且年龄较大的 PKU 患者，与匹配的对照组相比，超额费用主要来自住院治疗费用。
{"title":"Health economic impact of patients with phenylketonuria (PKU) in France – A nationwide study of health insurance claims data","authors":"","doi":"10.1016/j.ymgmr.2024.101134","DOIUrl":"10.1016/j.ymgmr.2024.101134","url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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; <em>p</em> < 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.</p><p>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; <em>p</em> < 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 < 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%).</p></div><div><h3>Conclusion</h3><p>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":null,"pages":null},"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}
Pub Date : 2024-08-14DOI: 10.1016/j.ymgmr.2024.101133
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.
{"title":"Diagnostic challenge of cutis Verticis Gyrata (CVG) in a patient presenting clinical features of Noonan or turner syndrome","authors":"","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":null,"pages":null},"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}
Pub Date : 2024-08-02DOI: 10.1016/j.ymgmr.2024.101127
Background and aims
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 MCCC1/MCCC2 variants. We investigated its incidence and features in Quanzhou, China.
Materials and methods
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 MCCC1/MCCC2 variants in suspected 3-MCCD cases.
Results
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.MCCC1and MCCC2 variants were found in 47.1% and 52.9% of patients,with c.1331G > A (31.3%) and c.351_353delTGG (50.0%) being the most prevalent, respectively. Clinical symptoms were observed in 11.8% of patients.
Conclusion
We identified six new MCCC1/MCCC2 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.
{"title":"Newborn screening and genetic diagnosis of 3-methylcrotonyl-CoA carboxylase deficiency in Quanzhou,China","authors":"","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 > 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":null,"pages":null},"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}
Pub Date : 2024-08-01DOI: 10.1016/j.ymgmr.2024.101080
Phenylketonuria (PKU) is an inborn error of amino acid metabolism that is typically identified by newborn screening. With lifelong treatment consisting of dietary management, frequent laboratory monitoring, and regular metabolic clinic visits, patients with PKU can maintain good health and metabolic control. Here, we describe the case of an 8-year-old patient with PKU who has been followed by a metabolic clinic since birth. Despite responsiveness to sapropterin, this patient has had periods of poor metabolic control throughout her life due to her family's economic hardships, including limited access to transportation, housing, food, and health insurance. This case illustrates how social determinants of health may negatively affect rare disease management and potential strategies for addressing barriers to care.
{"title":"Navigating social determinants of health barriers in the management of phenylketonuria","authors":"","doi":"10.1016/j.ymgmr.2024.101080","DOIUrl":"10.1016/j.ymgmr.2024.101080","url":null,"abstract":"<div><p>Phenylketonuria (PKU) is an inborn error of amino acid metabolism that is typically identified by newborn screening. With lifelong treatment consisting of dietary management, frequent laboratory monitoring, and regular metabolic clinic visits, patients with PKU can maintain good health and metabolic control. Here, we describe the case of an 8-year-old patient with PKU who has been followed by a metabolic clinic since birth. Despite responsiveness to sapropterin, this patient has had periods of poor metabolic control throughout her life due to her family's economic hardships, including limited access to transportation, housing, food, and health insurance. This case illustrates how social determinants of health may negatively affect rare disease management and potential strategies for addressing barriers to care.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000338/pdfft?md5=b1acd3c4849ed32c782aecfa45727869&pid=1-s2.0-S2214426924000338-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041199","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}
Pub Date : 2024-08-01DOI: 10.1016/j.ymgmr.2024.101121
A Black young adult female diagnosed with argininosuccinate lyase deficiency at 6 months of age encountered significant barriers to care for the first 16 years of her life due to socioeconomic factors and parental neglect. Once in the care of her paternal grandmother, she received appropriate treatment with a nitrogen scavenger, amino acid supplementation, and a low-protein diet. However, due to repeated hyperammonemic crises early in her life, she was minimally communicative and unable to perform activities of daily living. During her final hyperammonemic crisis, she presented to a hospital unfamiliar with urea cycle disorders and without a metabolic service. As a result, she did not receive optimal care and died.
{"title":"Fatal consequences of limited health literacy in a patient with a rare metabolic disease","authors":"","doi":"10.1016/j.ymgmr.2024.101121","DOIUrl":"10.1016/j.ymgmr.2024.101121","url":null,"abstract":"<div><p>A Black young adult female diagnosed with argininosuccinate lyase deficiency at 6 months of age encountered significant barriers to care for the first 16 years of her life due to socioeconomic factors and parental neglect. Once in the care of her paternal grandmother, she received appropriate treatment with a nitrogen scavenger, amino acid supplementation, and a low-protein diet. However, due to repeated hyperammonemic crises early in her life, she was minimally communicative and unable to perform activities of daily living. During her final hyperammonemic crisis, she presented to a hospital unfamiliar with urea cycle disorders and without a metabolic service. As a result, she did not receive optimal care and died.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000740/pdfft?md5=0f72a44cf784400fcb54d6647c86943c&pid=1-s2.0-S2214426924000740-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141706644","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}
Pub Date : 2024-08-01DOI: 10.1016/j.ymgmr.2024.101082
Social determinants of health (SDOH) are conditions in which people are born, grow, live, work, and age. Variations in these conditions are largely responsible for health inequities, the differences in health status or distribution of health resources within a population. Despite recent increases in attention to SDOH in research and clinical practice, few, if any, resources exist to describe how these complex dynamics impact patients with inborn errors of metabolism. Recognizing the role real-life narratives have as a powerful educational tool, we compiled a series of 3 original cases, published as part of this special supplement, to illustrate challenges and learnings related to SDOH within the context of urea cycle disorders and phenylketonuria.
{"title":"Treating the whole patient: Facilitating health care for patients facing health inequity","authors":"","doi":"10.1016/j.ymgmr.2024.101082","DOIUrl":"10.1016/j.ymgmr.2024.101082","url":null,"abstract":"<div><p>Social determinants of health (SDOH) are conditions in which people are born, grow, live, work, and age. Variations in these conditions are largely responsible for health inequities, the differences in health status or distribution of health resources within a population. Despite recent increases in attention to SDOH in research and clinical practice, few, if any, resources exist to describe how these complex dynamics impact patients with inborn errors of metabolism. Recognizing the role real-life narratives have as a powerful educational tool, we compiled a series of 3 original cases, published as part of this special supplement, to illustrate challenges and learnings related to SDOH within the context of urea cycle disorders and phenylketonuria.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000351/pdfft?md5=54c5e045100205fa5336d6906dce7d54&pid=1-s2.0-S2214426924000351-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757855","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}
Pub Date : 2024-08-01DOI: 10.1016/j.ymgmr.2024.101108
Argininosuccinic aciduria (ASA) is a disorder that results from a deficiency in the urea cycle enzyme argininosuccinate lyase. Variable manifestations of this hereditary disorder are associated with hyperammonemia and can include lethargy, somnolence, and respiratory alkalosis in neonates, and vomiting, headaches, and neurocognitive deficiencies later in life. Management of ASA includes rapid measures to address hyperammonemia and long-term steps to maintain metabolic stability. Management paradigms should also consider social determinants of health, which are non-medical factors that influence health outcomes. Here, we describe the case of a male pediatric patient with ASA whose treatment has included considerations for his family's refugee status, language barriers, cultural adjustments, limited income, and transportation challenges.
{"title":"Management of a urea cycle disorder in the setting of socioeconomic and language barriers","authors":"","doi":"10.1016/j.ymgmr.2024.101108","DOIUrl":"10.1016/j.ymgmr.2024.101108","url":null,"abstract":"<div><p>Argininosuccinic aciduria (ASA) is a disorder that results from a deficiency in the urea cycle enzyme argininosuccinate lyase. Variable manifestations of this hereditary disorder are associated with hyperammonemia and can include lethargy, somnolence, and respiratory alkalosis in neonates, and vomiting, headaches, and neurocognitive deficiencies later in life. Management of ASA includes rapid measures to address hyperammonemia and long-term steps to maintain metabolic stability. Management paradigms should also consider social determinants of health, which are non-medical factors that influence health outcomes. Here, we describe the case of a male pediatric patient with ASA whose treatment has included considerations for his family's refugee status, language barriers, cultural adjustments, limited income, and transportation challenges.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000612/pdfft?md5=9e4b03c24f392e7f05c1bb3933e325c5&pid=1-s2.0-S2214426924000612-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142149049","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}
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