Oculoleptomeningeal amyloidosis associated with transthyretin Leu12Pro mutation in a Chinese family

Objective To discuss the characteristics of clinical presentation, neuroimaging and genetics in a Chinese family of oculeptomeningeal amyloidosis (OLMA) associated with the transthyretin (TTR) Leu12Pro mutation. Methods Clinical characteristics of the pedigree and peripheral blood samples of an OLMA patient with TTR Leu12Pro mutation were collected from Tangdu Hospital on September 25, 2015. Firstly, exon detection was performed on the proband and the family validation of her father and sister was carried out. The clinical, neuroimaging and genetic characteristics of the disease were analyzed. Results A 36-year-old right-handed woman was suffered recurrent episodes of slurred speech with right-sided weakness. She presented initially with headache, autonomic dysfunction, visual and hearing loss. Magnetic resonance imaging showed extensive leptomeningeal enhancement, and cerebrospinal fluid analysis showed a raised protein of 1 566.54 mg/L. The examination of the both eyes showed dry eye, vitreous opacity, and mild cataract. The proband and her sister, the sister's eldest daughter, the proband's son showed c.95T>C mutation in exon2 of TTR gene and Leu12Pro mutation in TTR protein. Conclusions OLMA should be suspected if central nervous system symptoms are observed in combination with one or more of the following: family history of a neuropathy, autonomic dysfunction, cardiac hypertrophy, hear or ocular involvement, gadolinium-enhanced magnetic resonance imaging of the brain and spine revealing diffuse leptomeningeal enhancement, lumbar puncture demonstrating elevated protein without evidence of malignant cells on cytology. Genetic testing for pathogenic mutation in TTR gene is helpful for diagnosis of OLMA.