Case report and literature review of transthyretin amyloidosis with p.Ser43Asn mutation presenting in China.

BACKGROUND: Familial transthyretin amyloidosis (ATTR) is a rare hereditary disorder marked by abnormal protein fibril deposits that impair multiple organ functions. Although over 130 mutations have been identified, the p.Ser43Asn variant, which has been associated with amyloidosis involving thyroxine-binding globulin (TBG), is scarcely reported in the literature, especially within the Chinese population.

CASE PRESENTATION: We report a case of a 50-year-old male presenting with recurrent episodes of amaurosis fugax. The patient had a family history of cardiac disease. Auxiliary examinations revealed myocardial hypertrophy, and the electrocardiogram indicated conduction delays and abnormal QRS complexes. Nuclear imaging suggested cardiac amyloidosis, and cardiac MRI indicated non-ischemic cardiomyopathy. Genetic testing identified a c.128G > A (p.Ser43Asn) mutation, and pathological examination confirmed ATTR amyloidosis. Both pathological findings and mass spectrometry analysis supported this diagnosis.

DISCUSSION: The p.Ser43Asn variant likely impacts TTR protein dimerization and stability, leading to protein misfolding and amyloid fibril deposition in tissues. Early diagnosis is crucial due to the significant heterogeneity of this condition. Our findings emphasize the importance of increased diagnostic awareness, multidisciplinary collaboration, and regional genetic screening. Comparisons with similar cases reported in the literature highlight the shared clinical presentations and diagnostic challenges.

CONCLUSION: This case adds valuable insight into the clinical manifestations and diagnostic challenges of ATTR amyloidosis with the p.Ser43Asn mutation, particularly in the Chinese population. Future research should aim to develop effective treatment strategies and explore the genetic and environmental factors influencing the phenotypic variability of this rare disorder.