ATTR Epidemiology, Genetics, and Prognostic Factors

Chukwuemeka, Andrew; Mostertz, William C; Griffin, Jan M.; Judge, Daniel P.

doi:10.14797/mdcvj.1066

Cited by 46 publications

(41 citation statements)

References 73 publications

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“… 9 Thr80Ala is the second most common mutation in the USA, and this variant originated in the northern parts of the Republic of Ireland. 8 Symptoms in this cohort of patients typically present between 50 and 60 years of age, with predominantly neurologic and cardiac phenotypes. 1 TTR genetic testing is recommended for all patients with ATTR amyloidosis, particularly given that this has implications for first-degree relatives.…”

Section: Discussionmentioning

confidence: 89%

“… 7 Another case reported a Glu54Gly mutation in the TTR gene in a patient who had spontaneous periocular bruising. 8 Spontaneous periorbital purpura has not been described with the Thr80Ala mutation to our knowledge.…”

Section: Discussionmentioning

confidence: 90%

“… 1 Hereditary ATTR amyloidosis has an autosomal dominant pattern of inheritance. 8 The most common pathogenic TTR variant in the USA is the Val142Ile mutation, which occurs in 3.4% of African Americans. 9 Thr80Ala is the second most common mutation in the USA, and this variant originated in the northern parts of the Republic of Ireland.…”

Section: Discussionmentioning

confidence: 99%

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Hereditary transthyretin amyloidosis presenting with spontaneous periorbital purpura: a case report

Jhawar

Reynolds

Nakhleh

et al. 2023

European Heart Journal - Case Reports

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Background Amyloidosis is a systemic disorder of abnormal protein folding and deposition resulting in a range of symptoms including neuropathy, heart failure, renal disease, and dermatologic findings. The two most common types of amyloidosis that affect the heart are transthyretin (ATTR) amyloidosis and light chain (AL) amyloidosis, which vary in clinical presentation. Skin findings such as periorbital purpura are considered more specific for AL amyloidosis. However, there are rare cases of ATTR amyloidosis causing the same dermatologic findings. Case Summary A 69-year-old female presented for evaluation of amyloidosis after cardiac imaging done at the time of a recent atrial fibrillation ablation showed signs of infiltrative disease. On examination, she had periorbital purpura which she reportedly had for years without receiving a diagnosis, as well as macroglossia with teeth indentation. These exam findings, in addition to her transthoracic echocardiogram showing apical sparing, are typically considered characteristic of light chain amyloidosis. Subsequent workup revealed the presence of hereditary transthyretin amyloidosis (hATTR) with a heterozygous pathogenic variant in the TTR gene producing the p.Thr80Ala mutation. Conclusion Spontaneous periorbital purpura is thought to be pathognomonic for light chain (AL) amyloidosis. However, we describe a case of hereditary transthyretin amyloidosis (ATTR) with the Thr80Ala TTR genetic variant presenting initially with periorbital purpura, the first case documented in the literature to our knowledge.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 90%

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Hereditary transthyretin amyloidosis presenting with spontaneous periorbital purpura: a case report

Jhawar

Reynolds

Nakhleh

et al. 2023

European Heart Journal - Case Reports

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“…Hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy is a rare disease that has attracted attention in recent years due to novel disease-modifying medication and diagnostic tools. 1 This autosomaldominant disease is due to the accumulation of misfolded transthyretin proteins in the peripheral nerves and systemic organs. 2,3 The clinical manifestations of ATTRv amyloidosis are highly variable and are determined by the type of amyloid fibrils, tissue distribution, and amount of amyloid deposited.…”

Section: Introductionmentioning

confidence: 99%

Natural history and survival rate of familial amyloidosis with polyneuropathy: A nationwide databank

Tseng

Huang

et al. 2023

Ann Clin Transl Neurol

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Objective: Hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy, a rare autosomal-dominant disease, has gained attention in recent years owing to treatment improvements. However, epidemiological real-world mega database of nationwide natural history and survival rates, especially with the specific mutation of Ala97Ser, are limited. Methods: Taiwan National Health Insurance Research Database contains data from over 23 million individuals; Among them, 175 ATTRv amyloidosis patients validated by rare disease registry were enrolled. Multivariable Cox proportional hazard analyses were applied to investigate the association between baseline characteristics and allcause mortality. Findings: From 2008 to 2020, the annual incidence and prevalence rates of specific mutations (Ala97Ser) leading to ATTRv amyloidosis with polyneuropathy were 0.04-1.14 and 0.04-4.79 per million in Taiwan, respectively. In Taiwan, these patients exhibited male predominance with a mean age at validation of 62.75 years. At the 5th year after validation, patients exhibited a survival rate of approximately 50%, with higher mortality in male patients (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.15-4.31) and patients older at validation (HR: 1.10, 95% CI: 1.06-1.15). The two most common departments in outpatient were neurology and family medicine, and neurology and cardiology in inpatient. The three most common causes of death registered were unspecified amyloidosis (30.6%), organ-limited amyloidosis (20.9%), and neuropathic heredofamilial amyloidosis (9.7%). Interpretation: The annual prevalence rate of specific mutation (Ala97Ser)-dominant ATTRv amyloidosis with polyneuropathy in Taiwan is comparable to the mid-to high-prevalence country level of the research by Schmidt et al. The extraordinarily high mortality, especially among patients older at validation, may reflect the inadequate awareness and the necessity of early intervention with novel disease-modifying regimens.

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“…ATTRv is an underdiagnosed disease and the true incidence and prevalence are currently unknown ( Obi et al, 2022 ). Its global prevalence is traditionally and somewhat anecdotally estimated as 5,000 to 10,000 persons but only several countries in Europe and Japan have relatively exact prevalence ( Sousa et al, 1995 ; Kato-Motozaki et al, 2008 ; Dardiotis et al, 2009 ; Ines et al, 2018 ; Lauppe et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Prevalence estimation of ATTRv in China based on genetic databases

et al. 2023

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Introduction: Amyloid transthyretin (ATTR) is divided into either hereditary (ATTRv) or sporadic (ATTRwt) and ATTRv is a rare hereditary disease transmitted as an autosomal dominant manner. Its global prevalence is traditionally estimated as 5,000 to 10,000 persons. However, it may be underestimated and the exact prevalence of ATTRv in China mainland remains unknown.Methods: The Genome Aggregation database (gnomAD) database (containing 125,748 exomes) and two genomic sequencing databases——China Metabolic Analytics Project (ChinaMAP) (containing 10588 individuals) and Amcarelab gene database (containing 45392 exomes), were integrated to estimate the prevalence of ATTRv in the world and mainland Chinese populations. Pathogenic variants allele frequency and the prevalence of ATTRv was calculated.Results: Six variants, counting 470 alleles, were defined as pathogenic variants in gnomAD. The prevalence of ATTRv in the world population was 57.4/100,000. Two variants (2 allele counts) and 15 variants (34 individuals) were defined as pathogenic variants in the ChinaMAP database and the Amcarelab exome database, respectively. Thus, the estimated prevalence interval of ATTRv in mainland China was 18.9/100,000-74,9/100,000.Conclusion: The present study demonstrated that the previous prevalence was greatly underestimated using traditional methods. Therefore, raising awareness of the disease is essential for recognizing ATTRv in its early stage.

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ATTR Epidemiology, Genetics, and Prognostic Factors

Cited by 46 publications

References 73 publications

Hereditary transthyretin amyloidosis presenting with spontaneous periorbital purpura: a case report

Hereditary transthyretin amyloidosis presenting with spontaneous periorbital purpura: a case report

Natural history and survival rate of familial amyloidosis with polyneuropathy: A nationwide databank

Prevalence estimation of ATTRv in China based on genetic databases

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