Thoracic Aortic Dissection in a Patient With Classical Homocystinuria: Implications for Aortic Surveillance

Area of Science:

• Cardiovascular Medicine
• Metabolic Disorders
• Genetics

Background:

• Classical homocystinuria is an inherited metabolic disorder due to cystathionine beta-synthase (CBS) deficiency, leading to elevated homocysteine levels and multisystem complications.
• While its link to venous thromboembolism is known, the impact on aortic pathology is less understood.

Purpose of the Study:

• To report the first case of thoracic aortic dissection in a patient with classical homocystinuria.
• To investigate the potential role of elevated homocysteine in aortic pathology.

Main Methods:

• Case report of a 29-year-old female with classical homocystinuria.
• Post-mortem whole exome sequencing to identify pathogenic variants.
• Clinical review of patient history, including Marfanoid features, neurodevelopmental issues, obesity, and metabolic control.

Main Results:

• The patient experienced sudden death from a ruptured thoracic aortic dissection.
• Genetic analysis confirmed homozygosity for a pathogenic CBS mutation (NM_000071.2: c.1058C>T; p.(Thr353Met)) without other aortopathy-related variants.
• Elevated homocysteine levels were persistently noted despite diagnosis in childhood.

Conclusions:

• This case suggests elevated homocysteine may contribute to structural vascular damage, specifically aortic dissection.
• Aortic surveillance is recommended for classical homocystinuria patients, especially those with poor metabolic control or obesity.
• Early and sustained treatment is crucial for mitigating vascular risks in homocystinuria.