Case Report: Hereditary transthyretin amyloidosis in a Chinese family with the transthyretin variant p.Y89H

Abstract

Background Hereditary transthyretin amyloidosis (hATTR) is a rare, life-threatening multisystem disorder caused by pathogenic variants in the transthyretin (TTR) gene. Its clinical manifestations are highly heterogeneous, frequently resulting in diagnostic delay or misdiagnosis.hATTR caused by the TTR p.Y89H variant is extremely rare and is associated with a phenotype characterized by predominant ocular and leptomeningeal involvement. Case presentation A 59-year-old woman presented with a 10-year history of episodic headaches and a 3-year history of progressive bilateral visual decline. Brain computed tomography (CT) showed persistent diffuse leptomeningeal hyperdensities, and contrast-enhanced magnetic resonance imaging (MRI) revealed extensive, homogeneous enhancement of the cerebral and spinal leptomeninges. Genetic testing identified a heterozygous TTR variant, c.265 T > C (p.Y89H), in both the patient and her younger brother. The patient underwent left vitrectomy for vitreous opacities and received symptomatic treatment with ibuprofen for episodic headaches. Visual acuity in the left eye improved after vitrectomy, whereas visual acuity in the right eye continued to decline progressively during follow-up. CT obtained at one-year follow-up showed persistent leptomeningeal hyperdensities. Conclusion In the appropriate clinical and genetic context, persistent leptomeningeal hyperdensities on brain CT may serve as a diagnostic clue for p.Y89H-associated hATTR, although this finding should be interpreted cautiously and differentiated from other leptomeningeal pathologies. Patients with leptomeningeal hATTR may also be susceptible to contrast-induced encephalopathy.