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Massive leptomeningeal amyloidosis associated with a Val30Met transthyretin gene
M K Herrick1, K DeBruyne, D S Horoupian
1Department of Pathology, Santa Clara Valley Medical Center, San Jose, CA 95128-2699, USA.
Abstract:
We report a 69-year-old woman of Mexican origin with a 6-year history of progressive paresis, mild peripheral neuropathy, and recent onset of fluctuating mental status. Head and spinal MRI revealed contrast enhancing thickened meninges which on biopsy disclosed amyloid deposition. Immunohistochemistry identified the amyloid as transthyretin (TTR), and polymerase chain reaction/restriction fragment length polymorphism analysis of blood revealed a Val30Met mutation in one of her TTR genes. This mutation causes familial (hereditary) amyloidotic polyneuropathy of the Portuguese type (FAP 1). However, unlike FAP 1, in which peripheral neuropathy is a dominant feature, our patient's clinical manifestations, which included communicating hydrocephalus and myelopathy, were more suggestive of familial oculoleptomeningeal amyloidosis (FOLMA). In summary, the clinical presentation of TTR Met 30 mutation is more varied than previously suspected, and leptomeningeal amyloidosis should be considered in the differential diagnosis of obscure conditions involving meninges.
Insights
A rare genetic mutation (Val30Met in transthyretin) caused amyloidosis, affecting the brain's meninges. This case highlights the varied clinical presentations of this condition beyond typical neuropathy.
Area of Science:
- Neurology
- Genetics
- Pathology
Background:
- Familial amyloidotic polyneuropathy (Portuguese type, FAP 1) is typically characterized by progressive peripheral neuropathy.
- Transthyretin (TTR) Val30Met mutation is a known cause of hereditary amyloidosis.
- Leptomeningeal amyloidosis can present with diverse neurological symptoms.
Observation:
- A 69-year-old woman presented with progressive paresis, neuropathy, and altered mental status.
- MRI revealed contrast-enhancing thickened meninges, confirmed as amyloid deposition on biopsy.
- Immunohistochemistry and genetic analysis identified transthyretin (TTR) Val30Met mutation.
Findings:
- The patient's presentation, including hydrocephalus and myelopathy, differed from classic FAP 1, suggesting familial oculoleptomeningeal amyloidosis (FOLMA).
- The TTR Val30Met mutation demonstrated a broader clinical spectrum than previously recognized.
- Amyloid deposition in the meninges can manifest with varied neurological signs.
Implications:
- The clinical variability of TTR Met 30 mutation necessitates considering leptomeningeal amyloidosis in diagnosing obscure neurological conditions.
- This case expands the understanding of TTR-related amyloidosis phenotypes.
- Oculoleptomeningeal amyloidosis should be included in the differential diagnosis for patients with unexplained meningeal abnormalities.