Oculoleptomeningeal Amyloidosis Secondary to the Rare Transthyretin c.381T&gt;G (p.Ile127Met) Mutation

Mathieu, François; Morgan, Erin; So, Joyce; Muñoz, David G.; Mason, Warren P.; Kongkham, Paul

doi:10.1016/j.wneu.2017.12.096

Cited by 16 publications

(6 citation statements)

References 24 publications

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“…Some previous studies suggest LA cannot be blocked by liver transplantation as mutant TTR protein are mainly secreted from choroid plexus but not liver. 44 Given the associated imaging findings, patients with LA may be referred for consideration of neurosurgical intervention. Awareness of this rare pathology, and its consideration among the differential diagnosis, may limit unnecessary surgery in cases for which diagnosis can be made by less invasive means or through genetic testing.…”

Section: Discussionmentioning

confidence: 99%

Current Review of Leptomeningeal Amyloidosis Associated With Transthyretin Mutations

Qin

Wei

Piao³

et al. 2021

The Neurologist

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Introduction: Leptomeningeal amyloidosis (LA) represents a rare subtype of familial transthyretin (TTR) amyloidosis, characterized by deposition of amyloid in cranial and spinal leptomeninges. Of >120 TTR mutations identified, few have been associated with LA. Case Report: A 27-year-old male presented with a 2-year history of progressive symptoms including cognitive decline and right-sided weakness and numbness. Cerebrospinal fluid (CSF) analyses demonstrated high protein level. Gadolinium-enhanced magnetic resonance imaging (MRI) revealed extensive leptomeningeal enhancement over the surface of the brain and spinal cord. Pathologic analyses revealed a TTR mutation c.113A>G (p.D38G). Review Summary: Fifteen mutations and genotype-phenotype correlation of 72 LA patients have been summarized to provide an overview of LA associated with transthyretin mutations. The mean age of clinical onset was 44.9 years and the neurological symptoms primarily included cognitive impairment, headache, ataxia seizures and hearing, visual loss. CSF analysis showed elevated high CSF protein level and MRI revealed extensive leptomeningeal enhancement. Conclusion: Clinicians should be aware of this rare form of familial transthyretin amyloidosis as well as its typical MRI enhancement and high CSF protein. The important role of biopsy, genetic testing and the potential early diagnosis value of contrast MRI were suggested. Early recognition of these characteristics is important to provide misdiagnosis and shorten the time before correct diagnosis. These findings expand the phenotypic spectrum of TTR gene and have implications for the diagnosis, treatment, and systematic study of LA.

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Section: Discussionmentioning

confidence: 99%

Current Review of Leptomeningeal Amyloidosis Associated With Transthyretin Mutations

Qin

Wei

Piao³

et al. 2021

The Neurologist

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“…Ocular involvement is characterized by intraocular amyloid deposits related to the TTR production by the retinal epithelium, causing vitreous opacities, glaucoma and retinal amyloid angiopathy [19]. Few mutations are specifically associated with the exceptional oculoleptomeningeal disease form [20]. TTR production by choroid plexuses is the basis of the rare leptomeningeal variant, with amyloid deposition starting from leptomeningeal vessels and involving-in a centripetal progression along vessels-the brain parenchyma, and manifesting with seizures, hemorrhagic strokes, focal neurological episodes, dementia, ataxia, hydrocephalus, siderosis, calcifications and leptomeningeal enhancement [21].…”

Section: Gian Maria Fabrizi Marco Luigetti Paola Mandich Anna Mazzmentioning

confidence: 99%

Hereditary transthyretin amyloidosis overview

et al. 2020

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Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis is a rare autosomal dominantly inherited disorder caused by mutations in the transthyretin (TTR) gene. The pathogenetic model of ATTRv amyloidosis indicates that amyloidogenic, usually missense, mutations destabilize the native TTR favouring the dissociation of the tetramer into partially unfolded species that self-assemble into amyloid fibrils. Amyloid deposits and monomer-oligomer toxicity are the basis of multisystemic ATTRv clinical involvement. Peripheral nervous system (autonomic and somatic) and heart are the most affected sites. In the last decades, a better knowledge of pathomechanisms underlying the disease led to develop novel and promising drugs that are rapidly changing the natural history of ATTRv amyloidosis. Thus, clinicians face the challenge of timely diagnosis for addressing patients to appropriate treatment. As well, the progressive nature of ATTRv raises the issue of presymptomatic testing and risk management of carriers. The main aim of this review was to focus on what we know about ATTRv so far, from pathogenesis to clinical manifestations, diagnosis and hence patient’s monitoring and treatment, and from presymptomatic testing to management of carriers.

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“…[45][46][47] Central Nervous System Involvement TTR mutations with primarily central involvement due to production of TTR by the choroid plexus and/or retinal epithelium can lead to oculoleptomeningeal amyloidosis. 5,48 Multiple mutations have been reported, including Val30Gly, Asp18Gly, Leu12Pro, AL25Thr, Phe64Ser, Val127Met, Ala36-Pro, Tyr69His, Gly53Glu, Tyr114Cys variants, as well as Val30Met, [49][50][51][52][53][54][55] with a varied clinical spectrum that includes vitreous opacities, dementia, seizures, visual disturbances, ataxia, subarachnoid hemorrhage, hydrocephalus, and spasticity. Neuropathy may or may not be a concurrent feature.…”

Section: Other Neurologic Presentationsmentioning

confidence: 99%

Neuropathy Associated with Systemic Amyloidosis

Kaku

Berk

2019

Semin Neurol

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Peripheral neuropathy occurs in the setting of both hereditary and acquired amyloidosis. The most common form of hereditary amyloidosis is caused by 1 of 140 mutations in the transthyretin (TTR) gene, which can lead to neuropathic hereditary transthyretin amyloidosis (hATTR; previously referred to as transthyretin familial amyloid polyneuropathy), whereas acquired immunoglobulin light chain (AL) amyloidosis is the most common acquired form. Patients typically present with a sensorimotor polyneuropathy, focal neuropathy such as carpal tunnel syndrome, or autonomic neuropathy. When neuropathy is the sole or dominant presenting symptom, the diagnosis is commonly delayed. With the advent of new drug therapies for AL amyloidosis and hATTR amyloidosis, including proteasome inhibitors, TTR silencers, and TTR protein stabilizers, the neurologist is uniquely positioned to diagnose neurologic manifestations of systemic amyloidosis, leading to earlier disease identification and treatment. This article reviews the epidemiology, clinical presentations, pathophysiology, diagnostic workup, and treatment of neuropathy in the setting of amyloidosis.

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Oculoleptomeningeal Amyloidosis Secondary to the Rare Transthyretin c.381T>G (p.Ile127Met) Mutation

Cited by 16 publications

References 24 publications

Current Review of Leptomeningeal Amyloidosis Associated With Transthyretin Mutations

Current Review of Leptomeningeal Amyloidosis Associated With Transthyretin Mutations

Hereditary transthyretin amyloidosis overview

Neuropathy Associated with Systemic Amyloidosis

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