Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His

G. Blevins, R. Macaulay, S. Harder, D. Fladeland, T. Yamashita, M. Yazaki, K. Hamidi Asl, Merrill Benson, J. R. Donat

Research output: Contribution to journalArticle

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Abstract

Objective: To describe the clinical, radiologic, and pathologic findings of a kindred with oculoleptomeningeal amyloidosis and a newly associated transthyretin mutation. Background: Transthyretin (TTR) amyloidosis can present in the form of oculoleptomeningeal amyloidosis. Clinical features include dementia, seizures, stroke-like episodes, subarachnoid hemorrhage, ataxia, myelopathy, deafness, radiculopathy, and ocular amyloidosis. Eight TTR mutations associated with oculoleptomeningeal amyloidosis have been described. Methods: Fourteen individuals from a kindred with oculoleptomeningeal amyloidosis were examined clinically and radiologically. Analysis of the TTR gene was performed. Neuropathologic examination was obtained on the index patient. Results: Affected individuals had vitreous amyloid, radiculopathy, seizures, stroke-like episodes, encephalopathy, and dementia. Severely affected individuals died by the end of the fifth decade. Leptomeningeal enhancement on contrast MRI and elevated CSF protein were the defining features on investigations. Sequencing of exon 3 in the TTR gene found a base pair substitution at codon 69. This resulted in heterozygosity for normal tyrosine and variant histidine (ATTR Tyr69His) in affected family members. Domino liver transplantation was attempted as treatment for one family member. Conclusions: The ATTR Tyr69His mutation is associated with oculoleptomeningeal amyloidosis. Expression of the genotype is variable. This has implications for treatment of affected individuals and counseling of family members. Efficacy of liver transplantation in patients with oculoleptomeningeal amyloidosis remains unknown. The authors advocate the investigation of liver transplantation in patients with severe symptoms due to oculoleptomeningeal amyloidosis.

Original languageEnglish
Pages (from-to)1625-1630
Number of pages6
JournalNeurology
Volume60
Issue number10
StatePublished - May 27 2003

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Prealbumin
Amyloidosis
Liver Transplantation
Radiculopathy
Mutation
Dementia
Seizures
Stroke
Spinal Cord Diseases
Brain Diseases
Deafness
Subarachnoid Hemorrhage
Ataxia
Histidine
Amyloid
Codon
Base Pairing
Genes
Tyrosine
Counseling

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Blevins, G., Macaulay, R., Harder, S., Fladeland, D., Yamashita, T., Yazaki, M., ... Donat, J. R. (2003). Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His. Neurology, 60(10), 1625-1630.

Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His. / Blevins, G.; Macaulay, R.; Harder, S.; Fladeland, D.; Yamashita, T.; Yazaki, M.; Hamidi Asl, K.; Benson, Merrill; Donat, J. R.

In: Neurology, Vol. 60, No. 10, 27.05.2003, p. 1625-1630.

Research output: Contribution to journalArticle

Blevins, G, Macaulay, R, Harder, S, Fladeland, D, Yamashita, T, Yazaki, M, Hamidi Asl, K, Benson, M & Donat, JR 2003, 'Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His', Neurology, vol. 60, no. 10, pp. 1625-1630.
Blevins G, Macaulay R, Harder S, Fladeland D, Yamashita T, Yazaki M et al. Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His. Neurology. 2003 May 27;60(10):1625-1630.
Blevins, G. ; Macaulay, R. ; Harder, S. ; Fladeland, D. ; Yamashita, T. ; Yazaki, M. ; Hamidi Asl, K. ; Benson, Merrill ; Donat, J. R. / Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His. In: Neurology. 2003 ; Vol. 60, No. 10. pp. 1625-1630.
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abstract = "Objective: To describe the clinical, radiologic, and pathologic findings of a kindred with oculoleptomeningeal amyloidosis and a newly associated transthyretin mutation. Background: Transthyretin (TTR) amyloidosis can present in the form of oculoleptomeningeal amyloidosis. Clinical features include dementia, seizures, stroke-like episodes, subarachnoid hemorrhage, ataxia, myelopathy, deafness, radiculopathy, and ocular amyloidosis. Eight TTR mutations associated with oculoleptomeningeal amyloidosis have been described. Methods: Fourteen individuals from a kindred with oculoleptomeningeal amyloidosis were examined clinically and radiologically. Analysis of the TTR gene was performed. Neuropathologic examination was obtained on the index patient. Results: Affected individuals had vitreous amyloid, radiculopathy, seizures, stroke-like episodes, encephalopathy, and dementia. Severely affected individuals died by the end of the fifth decade. Leptomeningeal enhancement on contrast MRI and elevated CSF protein were the defining features on investigations. Sequencing of exon 3 in the TTR gene found a base pair substitution at codon 69. This resulted in heterozygosity for normal tyrosine and variant histidine (ATTR Tyr69His) in affected family members. Domino liver transplantation was attempted as treatment for one family member. Conclusions: The ATTR Tyr69His mutation is associated with oculoleptomeningeal amyloidosis. Expression of the genotype is variable. This has implications for treatment of affected individuals and counseling of family members. Efficacy of liver transplantation in patients with oculoleptomeningeal amyloidosis remains unknown. The authors advocate the investigation of liver transplantation in patients with severe symptoms due to oculoleptomeningeal amyloidosis.",
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AU - Blevins, G.

AU - Macaulay, R.

AU - Harder, S.

AU - Fladeland, D.

AU - Yamashita, T.

AU - Yazaki, M.

AU - Hamidi Asl, K.

AU - Benson, Merrill

AU - Donat, J. R.

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N2 - Objective: To describe the clinical, radiologic, and pathologic findings of a kindred with oculoleptomeningeal amyloidosis and a newly associated transthyretin mutation. Background: Transthyretin (TTR) amyloidosis can present in the form of oculoleptomeningeal amyloidosis. Clinical features include dementia, seizures, stroke-like episodes, subarachnoid hemorrhage, ataxia, myelopathy, deafness, radiculopathy, and ocular amyloidosis. Eight TTR mutations associated with oculoleptomeningeal amyloidosis have been described. Methods: Fourteen individuals from a kindred with oculoleptomeningeal amyloidosis were examined clinically and radiologically. Analysis of the TTR gene was performed. Neuropathologic examination was obtained on the index patient. Results: Affected individuals had vitreous amyloid, radiculopathy, seizures, stroke-like episodes, encephalopathy, and dementia. Severely affected individuals died by the end of the fifth decade. Leptomeningeal enhancement on contrast MRI and elevated CSF protein were the defining features on investigations. Sequencing of exon 3 in the TTR gene found a base pair substitution at codon 69. This resulted in heterozygosity for normal tyrosine and variant histidine (ATTR Tyr69His) in affected family members. Domino liver transplantation was attempted as treatment for one family member. Conclusions: The ATTR Tyr69His mutation is associated with oculoleptomeningeal amyloidosis. Expression of the genotype is variable. This has implications for treatment of affected individuals and counseling of family members. Efficacy of liver transplantation in patients with oculoleptomeningeal amyloidosis remains unknown. The authors advocate the investigation of liver transplantation in patients with severe symptoms due to oculoleptomeningeal amyloidosis.

AB - Objective: To describe the clinical, radiologic, and pathologic findings of a kindred with oculoleptomeningeal amyloidosis and a newly associated transthyretin mutation. Background: Transthyretin (TTR) amyloidosis can present in the form of oculoleptomeningeal amyloidosis. Clinical features include dementia, seizures, stroke-like episodes, subarachnoid hemorrhage, ataxia, myelopathy, deafness, radiculopathy, and ocular amyloidosis. Eight TTR mutations associated with oculoleptomeningeal amyloidosis have been described. Methods: Fourteen individuals from a kindred with oculoleptomeningeal amyloidosis were examined clinically and radiologically. Analysis of the TTR gene was performed. Neuropathologic examination was obtained on the index patient. Results: Affected individuals had vitreous amyloid, radiculopathy, seizures, stroke-like episodes, encephalopathy, and dementia. Severely affected individuals died by the end of the fifth decade. Leptomeningeal enhancement on contrast MRI and elevated CSF protein were the defining features on investigations. Sequencing of exon 3 in the TTR gene found a base pair substitution at codon 69. This resulted in heterozygosity for normal tyrosine and variant histidine (ATTR Tyr69His) in affected family members. Domino liver transplantation was attempted as treatment for one family member. Conclusions: The ATTR Tyr69His mutation is associated with oculoleptomeningeal amyloidosis. Expression of the genotype is variable. This has implications for treatment of affected individuals and counseling of family members. Efficacy of liver transplantation in patients with oculoleptomeningeal amyloidosis remains unknown. The authors advocate the investigation of liver transplantation in patients with severe symptoms due to oculoleptomeningeal amyloidosis.

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