Pub Date : 2026-01-01Epub Date: 2026-01-06DOI: 10.7326/aimcc.2025.0735
Mohammad Karam Chaaban, George Bcharah, Bukola A Olarewaju, Linnea M Baudhuin, Fadi Shamoun, Mayowa A Osundiji
Roundabout guidance receptor 4 (ROBO4) germline variants [including c.695C>T (p.Thr232Met)] have been linked with bicuspid aortic valve and thoracic aortic aneurysm. However, the precise nature of ROBO4's role in aortopathy is yet to be fully defined. We studied a 64-year-old woman with a history of surgically corrected congenital aortic coarctation in childhood, bicuspid aortic valve, and mild mitral regurgitation. She had genome sequencing, which revealed a heterozygous germline ROBO4 variant [c.695C>T (p.Thr232Met)]. Our findings suggest that the spectrum of aortic abnormalities that are associated with ROBO4 germline variants may include congenital coarctation of the aorta.
环形引导受体4 （ROBO4）种系变异[包括c.695C >t (p.Thr232Met)]与二尖瓣主动脉瓣和胸主动脉瘤有关。然而，ROBO4在主动脉病变中作用的确切性质尚未完全确定。我们研究了一名64岁的女性，她有手术纠正的儿童先天性主动脉缩窄史，二尖瓣主动脉瓣，轻度二尖瓣反流。她进行了基因组测序，发现了一种杂合的种系ROBO4变异[c]。695 c > T (p.Thr232Met)]。我们的研究结果表明，与ROBO4种系变异相关的主动脉异常谱可能包括先天性主动脉缩窄。
{"title":"Congenital Coarctation of the Aorta in a Patient With <i>ROBO4</i> c.695C>T (p.Thr232Met) Germline Variant.","authors":"Mohammad Karam Chaaban, George Bcharah, Bukola A Olarewaju, Linnea M Baudhuin, Fadi Shamoun, Mayowa A Osundiji","doi":"10.7326/aimcc.2025.0735","DOIUrl":"10.7326/aimcc.2025.0735","url":null,"abstract":"<p><p>Roundabout guidance receptor 4 (<i>ROBO4</i>) germline variants [including c.695C>T (p.Thr232Met)] have been linked with bicuspid aortic valve and thoracic aortic aneurysm. However, the precise nature of <i>ROBO4</i>'s role in aortopathy is yet to be fully defined. We studied a 64-year-old woman with a history of surgically corrected congenital aortic coarctation in childhood, bicuspid aortic valve, and mild mitral regurgitation. She had genome sequencing, which revealed a heterozygous germline <i>ROBO4</i> variant [c.695C>T (p.Thr232Met)]. Our findings suggest that the spectrum of aortic abnormalities that are associated with <i>ROBO4</i> germline variants may include congenital coarctation of the aorta.</p>","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12851620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-08-05DOI: 10.7326/aimcc.2025.0080
Mayowa A Osundiji, Alicia Chen, Joseph D Farris, Radhika Dhamija
Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHS) deficiency is an ultra-rare inborn error of ketone body synthesis that is caused by biallelic mutations in HMGCS2. The manifestations of mHS deficiency can include hypoketotic hypoglycemia, metabolic acidosis, lethargy, encephalopathy, hyperammonemia, and hepatomegaly. Here, we report a case of movement disorder following hypoglycemic encephalopathy involving the basal ganglia in a patient with mHS deficiency. Exome sequencing showed novel compound heterozygous variants in HMGCS2, a partial gene deletion (classified as pathogenic) and c.704T>A (p.M235K) variant that was deemed to be likely pathogenic. Our findings suggest that mHS deficiency can result in basal ganglia injury and movement disorder.
线粒体3-羟基-3-甲基戊二酰辅酶A合成酶（mHS）缺乏症是一种极为罕见的先天性酮体合成错误，由HMGCS2的双等位基因突变引起。mHS缺乏的表现包括低酮性低血糖、代谢性酸中毒、嗜睡、脑病、高氨血症和肝肿大。在这里，我们报告一例低血糖性脑病累及基底神经节的mHS缺乏症患者的运动障碍。外显子组测序显示HMGCS2中存在新的复合杂合变异，部分基因缺失（归类为致病性）和c.704T> a （p.M235K）变异被认为可能具有致病性。我们的研究结果表明，mHS缺乏可导致基底神经节损伤和运动障碍。
{"title":"Movement Disorder Following Hypoglycemic Encephalopathy in Mitochondrial 3-Hydroxy-3-methylglutaryl-CoA Synthase-2 (mHS) Deficiency.","authors":"Mayowa A Osundiji, Alicia Chen, Joseph D Farris, Radhika Dhamija","doi":"10.7326/aimcc.2025.0080","DOIUrl":"https://doi.org/10.7326/aimcc.2025.0080","url":null,"abstract":"<p><p>Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHS) deficiency is an ultra-rare inborn error of ketone body synthesis that is caused by biallelic mutations in <i>HMGCS2</i>. The manifestations of mHS deficiency can include hypoketotic hypoglycemia, metabolic acidosis, lethargy, encephalopathy, hyperammonemia, and hepatomegaly. Here, we report a case of movement disorder following hypoglycemic encephalopathy involving the basal ganglia in a patient with mHS deficiency. Exome sequencing showed novel compound heterozygous variants in <i>HMGCS2</i>, a partial gene deletion (classified as pathogenic) and c.704T>A (p.M235K) variant that was deemed to be likely pathogenic. Our findings suggest that mHS deficiency can result in basal ganglia injury and movement disorder.</p>","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"4 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-05-07DOI: 10.7326/aimcc.2023.1141
Neeharika Namineni, Christina Waldron, Christopher Tormey, George Goshua
A previously healthy 60-year-old man presented to the hospital with a hemoglobin of 3.5 g/dL. He was diagnosed with severe warm autoimmune hemolytic anemia (wAIHA) with reticulocytopenia on hospital day 1 that was not responsive to steroids, immune globulin, and rituximab. Over a 42-day hospital stay, the patient remained continuously transfusion-dependent with a ninety red cell unit requirement for his refractory disease. He was trialed on therapeutic plasma exchange before ultimately undergoing inpatient splenectomy that led to a response within hours. He remains in complete remission at six months of follow-up.
{"title":"Severe, Refractory Primary Warm Autoimmune Hemolytic Anemia Requiring 90 Erythrocyte Transfusions.","authors":"Neeharika Namineni, Christina Waldron, Christopher Tormey, George Goshua","doi":"10.7326/aimcc.2023.1141","DOIUrl":"10.7326/aimcc.2023.1141","url":null,"abstract":"<p><p>A previously healthy 60-year-old man presented to the hospital with a hemoglobin of 3.5 g/dL. He was diagnosed with severe warm autoimmune hemolytic anemia (wAIHA) with reticulocytopenia on hospital day 1 that was not responsive to steroids, immune globulin, and rituximab. Over a 42-day hospital stay, the patient remained continuously transfusion-dependent with a ninety red cell unit requirement for his refractory disease. He was trialed on therapeutic plasma exchange before ultimately undergoing inpatient splenectomy that led to a response within hours. He remains in complete remission at six months of follow-up.</p>","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"3 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11081177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fátima Raad, Vicente Ramos Polledo, Andreu Fernández-Codina, Fernando De La Iglesia Martínez
Giant-cell arteritis (GCA) is a medium- to large-vessel arteritis predominantly involving the branches of the aorta, occurring in elderly patients. Findings in GCA include symptoms such as headache, jaw claudication, or polymyalgia rheumatica; ischemic events; and signs of a systemic inflammatory reaction. The clinical presentation may rarely involve other areas. We report the case of an 85-year-old man with biopsy-proven GCA presenting with fever, weight loss, and scalp necrosis.
{"title":"Ischemic Complications of Giant-Cell Arteritis","authors":"Fátima Raad, Vicente Ramos Polledo, Andreu Fernández-Codina, Fernando De La Iglesia Martínez","doi":"10.7326/aimcc.2023.0560","DOIUrl":"https://doi.org/10.7326/aimcc.2023.0560","url":null,"abstract":"Giant-cell arteritis (GCA) is a medium- to large-vessel arteritis predominantly involving the branches of the aorta, occurring in elderly patients. Findings in GCA include symptoms such as headache, jaw claudication, or polymyalgia rheumatica; ischemic events; and signs of a systemic inflammatory reaction. The clinical presentation may rarely involve other areas. We report the case of an 85-year-old man with biopsy-proven GCA presenting with fever, weight loss, and scalp necrosis.","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"26 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombotic thrombocytopenic purpura (TTP) can present with neurologic symptoms before the development of typical hematologic abnormalities. We describe a patient presenting with decreased grip strength in his right hand who was found to have an ischemic stroke from acute TTP. In the setting of subtle hematologic abnormalities, detection of severely decreased ADAMTS13 activity aided in early diagnosis and prompt initiation of plasmapheresis. Hence, we emphasize the need for high clinical suspicion for TTP in patients with recurrent and cryptogenic strokes, especially in the setting of subtle hematologic findings, as early treatment decreases mortality rate by almost 90%.
{"title":"Recurrent Strokes in a Hypertensive Smoker: An Atypical Case and Review of Thrombotic Thrombocytopenic Purpura","authors":"Nithya Ramesh, Shanjeev Kumar Rajeshkumar Chitra, Udunma Ikoro, Sohiel Deshpande, Vartika Singh, Vidhi Mehta, Andre Posner","doi":"10.7326/aimcc.2023.0424","DOIUrl":"https://doi.org/10.7326/aimcc.2023.0424","url":null,"abstract":"Thrombotic thrombocytopenic purpura (TTP) can present with neurologic symptoms before the development of typical hematologic abnormalities. We describe a patient presenting with decreased grip strength in his right hand who was found to have an ischemic stroke from acute TTP. In the setting of subtle hematologic abnormalities, detection of severely decreased ADAMTS13 activity aided in early diagnosis and prompt initiation of plasmapheresis. Hence, we emphasize the need for high clinical suspicion for TTP in patients with recurrent and cryptogenic strokes, especially in the setting of subtle hematologic findings, as early treatment decreases mortality rate by almost 90%.","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"27 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Right ventricular air embolism is a rare and dangerous condition that frequently presents with nonspecific symptoms, making diagnosis difficult. We present a case involving a young woman with concerning symptoms following routine injection of contrast. Computed tomography scan visualizing the heart confirmed the finding of a large air embolism. We describe the immediate actions taken and the subsequent treatment provided.
{"title":"Recognition and Treatment of a Right Ventricular Air Embolism","authors":"Leon Sun, Katherine I. Harris","doi":"10.7326/aimcc.2023.0817","DOIUrl":"https://doi.org/10.7326/aimcc.2023.0817","url":null,"abstract":"Right ventricular air embolism is a rare and dangerous condition that frequently presents with nonspecific symptoms, making diagnosis difficult. We present a case involving a young woman with concerning symptoms following routine injection of contrast. Computed tomography scan visualizing the heart confirmed the finding of a large air embolism. We describe the immediate actions taken and the subsequent treatment provided.","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tarika D. Patel, Meagan N. McNicholas, Christina M. Laukaitis
Loeys–Dietz syndrome (LDS) 5 is characterized by aortic aneurysms, hypertelorism, and cleft palate/bifid uvula. We describe a woman with a transforming growth factor beta3 (TGFβ3) mutation who displays a forme fruste phenotype of LDS5. A 43-year-old woman with joint pain and hypermobile joints underwent evaluation for hypermobile Ehlers–Danlos syndrome. Her features included pes planus, treated high-arched palate, and increased joint mobility. Genetic analysis identified a pathogenic TGFβ3 variant (c.427A>T, p.Arg143*), clarifying the diagnosis of LDS5. Comparing our patient with others with TGFB3 mutations illustrated the diversity of LDS5 features, often a milder forme fruste form, which warrants more investigation due to insufficient characterization.
{"title":"A Heterozygous Variant of <i>TGFB3</i> in a Patient With an Atypical Presentation of Loeys–Dietz Syndrome: A Case Report","authors":"Tarika D. Patel, Meagan N. McNicholas, Christina M. Laukaitis","doi":"10.7326/aimcc.2023.0035","DOIUrl":"https://doi.org/10.7326/aimcc.2023.0035","url":null,"abstract":"Loeys–Dietz syndrome (LDS) 5 is characterized by aortic aneurysms, hypertelorism, and cleft palate/bifid uvula. We describe a woman with a transforming growth factor beta3 (TGFβ3) mutation who displays a forme fruste phenotype of LDS5. A 43-year-old woman with joint pain and hypermobile joints underwent evaluation for hypermobile Ehlers–Danlos syndrome. Her features included pes planus, treated high-arched palate, and increased joint mobility. Genetic analysis identified a pathogenic TGFβ3 variant (c.427A>T, p.Arg143*), clarifying the diagnosis of LDS5. Comparing our patient with others with TGFB3 mutations illustrated the diversity of LDS5 features, often a milder forme fruste form, which warrants more investigation due to insufficient characterization.","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"23 12","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kim L. Tran, Seema R. Walvekar, Brian C. Boulmay, Sarah W. Lungaro, Jasmine L. Taylor
{"title":"Paraneoplastic Leukemoid Reaction in High-Grade Lung Adenocarcinoma Complicated by Triple Co-Mutations","authors":"Kim L. Tran, Seema R. Walvekar, Brian C. Boulmay, Sarah W. Lungaro, Jasmine L. Taylor","doi":"10.7326/aimcc.2023.0502","DOIUrl":"https://doi.org/10.7326/aimcc.2023.0502","url":null,"abstract":"","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"27 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amirhossein Esmaeeli, Prashant Nagpal, Jefree J. Schulte, Sofia C. Masri, Peter S. Rahko
Glycogen storage disease cardiomyopathy is being recognized increasingly as a mimicker of hypertrophic cardiomyopathy. It is important to diagnose these diseases, as there are prognostic and treatment ramifications. This case report discusses a patient who presented with cardioembolic renal infarction and was ultimately diagnosed with glycogen storage disease XV (which is extremely rare). The diagnosis was made by pursuing multimodality imaging, endomyocardial biopsy, and genetic testing.
{"title":"Systemic Emboli and Biventricular Hypertrophy Due to Glycogen Storage Disease: Clinical, Imaging, and Pathologic Predicament","authors":"Amirhossein Esmaeeli, Prashant Nagpal, Jefree J. Schulte, Sofia C. Masri, Peter S. Rahko","doi":"10.7326/aimcc.2023.0463","DOIUrl":"https://doi.org/10.7326/aimcc.2023.0463","url":null,"abstract":"Glycogen storage disease cardiomyopathy is being recognized increasingly as a mimicker of hypertrophic cardiomyopathy. It is important to diagnose these diseases, as there are prognostic and treatment ramifications. This case report discusses a patient who presented with cardioembolic renal infarction and was ultimately diagnosed with glycogen storage disease XV (which is extremely rare). The diagnosis was made by pursuing multimodality imaging, endomyocardial biopsy, and genetic testing.","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"24 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endoscopic transpapillary gallbladder drainage is considered an alternative procedure in patients with acute cholecystitis who are not surgical candidates; however, it remains challenging, especially in cases with a stone impacted into the cystic duct (CD). In cases in which a stone is impacted at the CD orifice, a cholangioscope and forceps may be used to release the stone. In cases in which the stone is impacted in the middle of the CD, contrast pressure from above the injection retrieval balloon may be used to push the stone toward the gallbladder. We believe this is the first report of such cases in the literature.
{"title":"Endoscopic Troubleshooting for Acute Cholecystitis With a Stone Impacted in the Cystic Duct","authors":"Sakue Masuda, Kazuya Koizumi, Takayoshi Tsuchiya, Makomo Makazu, Ryuuhei Jinushi, Kento Shionoya, Karen Kimura, Takashi Nishino, Chikamasa Ichita, Akiko Sasaki","doi":"10.7326/aimcc.2023.0101","DOIUrl":"https://doi.org/10.7326/aimcc.2023.0101","url":null,"abstract":"Endoscopic transpapillary gallbladder drainage is considered an alternative procedure in patients with acute cholecystitis who are not surgical candidates; however, it remains challenging, especially in cases with a stone impacted into the cystic duct (CD). In cases in which a stone is impacted at the CD orifice, a cholangioscope and forceps may be used to release the stone. In cases in which the stone is impacted in the middle of the CD, contrast pressure from above the injection retrieval balloon may be used to push the stone toward the gallbladder. We believe this is the first report of such cases in the literature.","PeriodicalId":72222,"journal":{"name":"Annals of internal medicine. Clinical cases","volume":"24 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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