Key Information
Source
Year
2024
summary/abstract
Hereditary transthyretinexternal link, opens in a new tab amyloidosis is autosomal dominantexternal link, opens in a new tab and results from mutations in the transthyretinexternal link, opens in a new tab gene. The Val30Met variant is the most common genetic mutationexternal link, opens in a new tab, although mutations vary within populations. More than 150 mutations in transthyretin have been reported; however, the Leu111Glu (p. Leu131Glu) mutation has been reported to date. We report the case of a 32-year-old Japanese male with a history of cerebral hemorrhageexternal link, opens in a new tab and hydrocephalusexternal link, opens in a new tab at age 27 years. The patient was referred to our department after his sibling had been diagnosed with hereditary transthyretin amyloidosisexternal link, opens in a new tab. Twelve-lead electrocardiography exhibited poor R progression, and transthoracic echocardiographyexternal link, opens in a new tab showed normal findings. 99mTc-labelled pyrophosphateexternal link, opens in a new tab scintigraphyexternal link, opens in a new tab showed high accumulation in the heart. Histological tests using a right ventricular endomyocardial biopsyexternal link, opens in a new tab showed amyloid deposits and immunostainingexternal link, opens in a new tab only for transthyretin. Genetic analysis confirmed a novel missense variant, Leu111Glu, on the transthyretin gene. We diagnosed the patient with hereditary transthyretin amyloidosisexternal link, opens in a new tab, and the patient received genetic counseling. Patients with hereditary transthyretin amyloidosis carrying the Leu111Gln variant may present as a patient with a hydrocephalus-dominant phenotype. To the best of our knowledge, this is the first case report of the transthyretin Leu111Glu variant.
Learning objective
Hereditary transthyretin amyloidosis with the Leu111Gln variant has not been previously reported in Japan. While cardiac involvement progresses without overt abnormal findings on electrocardiogram and echocardiogramexternal link, opens in a new tab, 99mTc-labelled pyrophosphateexternal link, opens in a new tab scintigraphy can be a useful tool for the early diagnosis of hereditary transthyretin amyloidosis. This mutation may result in a predominantly hydrocephalusexternal link, opens in a new tab phenotype, and organ damage is expected to progress rapidly. Therefore, early diagnosis and appropriate treatment are necessary.