2026/07/01 by Marisa Chard, Jasmin Simi Zhang, Lesley Turner · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Alcoholism and Thiamine Deficiency #Folate and B Vitamins Research #Metabolism and Genetic Disorders
paper · doi:10.1002/jmd2.70107
openalex publication_date 2026/07/01 · openalex created_date 2026/07/20 · openalex updated_date 2026/08/01
ABSTRACT Classical homocystinuria (OMIM #236300), a rare inherited metabolic disorder caused by cystathionine beta‐synthase (CBS) deficiency, is characterized by markedly elevated homocysteine levels and associated multisystem complications. While the role of homocystinuria in venous thromboembolism is well recognized, there is limited evidence of impact on aortic pathology. We report the first known case of thoracic aortic dissection in a patient with poorly controlled classical homocystinuria. The patient, a 29‐year‐old female, was diagnosed in childhood after presenting with Marfanoid features and neurodevelopmental issues, and had persistently elevated homocysteine levels. She had morbid obesity (BMI: 52.7 kg/m 2 ) with no known hypertension or aortic disease. She died suddenly from a ruptured thoracic aortic dissection. Post‐mortem whole exome sequencing confirmed homozygosity for a pathogenic CBS mutation NM000071.2: c.1058C>T; p.(Thr353Met) without any additional variants implicated in monogenic aortopathy or aortic dissection. Notably, her younger brother also has classical homocystinuria but no evidence of aortic dilation to date. This case adds to emerging evidence that elevated homocysteine may contribute to structural vascular damage. Our findings underscore the need to consider aortic surveillance in patients with classical homocystinuria, particularly those with inadequate metabolic control or additional risk factors such as obesity, and highlight the importance of early, sustained treatment to mitigate potential vascular risk.