Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain.
CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.
Amyloid. 2023 Jun;30(2):199-207. doi: 10.1080/13506129.2022.2142110. Epub 2022 Nov 7.
The p.Glu109Lys variant (Glu89Lys) is a rare cause of hereditary transthyretin amyloidosis (ATTRv) for which clinical spectrum remains unresolved. We sought to describe the clinical characteristics and outcomes of ATTR Glu89Lys amyloidosis and assess a potential founder effect in Spain.
Patients with the p.Glu109Lys ATTRv variant from 14 families were recruited at 7 centres. Demographics, complementary tests and clinical course were analysed. Haplotype analysis was performed in 7 unrelated individuals.
Thirty-eight individuals (13 probands, mean age 40.4 ± 13.1 years) were studied. After median follow-up of 5.1 years (IQR 1.7-9.6), 7 patients died and 7 required heart transplantation (median age at transplantation 50.5 years). Onset of cardiac and neurological manifestations occurred at a mean age of 48.4 and 46.8 years, respectively. Median survival from birth was 61.6 years and no individual survived beyond 65 years. Patients treated with disease-modifying therapies exhibited better prognosis ( < 0.001). Haplotype analysis revealed a common origin from an ancestor who lived ∼500 years ago in southeast Spain.
Glu89Lys ATTRv is a variant with a founder effect in Spain. It is associated with near complete penetrance, early onset and mixed cardiac and neurologic phenotype. Patients have poor prognosis, particularly if not treated with disease-modifying therapies.
Glu109Lys 变异（Glu89Lys）是一种罕见的遗传性转甲状腺素蛋白淀粉样变性（ATTRv）的病因，其临床表现仍未明确。我们旨在描述 ATTR Glu89Lys 淀粉样变性的临床特征和结局，并评估西班牙是否存在潜在的起源效应。
在 7 个中心招募了 14 个家族的 p.Glu109Lys ATTRv 变异患者。分析了人口统计学、补充检查和临床病程。对 7 个无关个体进行单体型分析。
共纳入 38 名个体（13 名先证者，平均年龄 40.4±13.1 岁）。中位随访 5.1 年后（IQR 1.7-9.6），7 名患者死亡，7 名患者需要心脏移植（中位移植年龄 50.5 岁）。心脏和神经表现的发病年龄分别为平均 48.4 岁和 46.8 岁。从出生起的中位总生存期为 61.6 年，没有个体存活超过 65 岁。接受疾病修正治疗的患者预后更好（ < 0.001）。单体型分析显示存在一个共同的起源，起源于大约 500 年前西班牙东南部的一个祖先。
Glu89Lys ATTRv 是一种在西班牙具有起源效应的变异体。它与近乎完全外显率、早发和混合性心脏和神经表型相关。如果不接受疾病修正治疗，患者预后较差。
