title: Oculoleptomeningeal Amyloidosis associated with transthyretin Leu12Pro in an African patient.
abstract: Oculoleptomeningeal amyloidosis is a rare manifestation of hereditary transthyretin (TTR) amyloidosis. Here, we present the first case of leptomeningeal amyloidosis associated with the TTR variant Leu12Pro mutation in an African patient. A 43-year-old right-handed Nigerian man was referred to our centre with rapidly progressive neurological decline. He presented initially with weight loss, confusion, fatigue, and urinary and erectile dysfunction. He then suffered recurrent episodes of slurred speech with right-sided weakness. He went on to develop hearing difficulties and painless paraesthesia. Neurological examination revealed horizontal gaze-evoked nystagmus, brisk jaw jerk, increased tone, brisk reflexes throughout and bilateral heel-shin ataxia. Magnetic resonance imaging showed extensive leptomeningeal enhancement. Cerebrospinal fluid analysis showed a raised protein of 6.4 g/dl. Nerve conduction studies showed an axonal neuropathy. Echocardiography was characteristic of cardiac amyloid. TTR gene sequencing showed that he was heterozygous for the leucine 12 proline mutation. Meningeal and brain biopsy confirmed widespread amyloid angiopathy. TTR amyloidosis is a rare cause of leptomeningeal enhancement, but should be considered if there is evidence of peripheral or autonomic neuropathy with cardiac or ocular involvement. The relationship between different TTR mutations and clinical phenotype, disease course, and response to treatment remains unclear.
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK, p.mccolgan@ucl.ac.uk.
authors.forename: P
authors.initials: P
authors.lastname: McColgan
authors.forename: S
authors.initials: S
authors.lastname: Viegas
authors.forename: S
authors.initials: S
authors.lastname: Gandhi
authors.forename: K
authors.initials: K
authors.lastname: Bull
authors.forename: R
authors.initials: R
authors.lastname: Tudor
authors.forename: F
authors.initials: F
authors.lastname: Sheikh
authors.forename: J
authors.initials: J
authors.lastname: Pinney
authors.forename: M
authors.initials: M
authors.lastname: Fontana
authors.forename: D
authors.initials: D
authors.lastname: Rowczenio
authors.forename: J D
authors.initials: JD
authors.lastname: Gillmore
authors.forename: J A
authors.initials: JA
authors.lastname: Gilbertson
authors.forename: C J
authors.initials: CJ
authors.lastname: Whelan
authors.forename: S
authors.initials: S
authors.lastname: Shah
authors.forename: Z
authors.initials: Z
authors.lastname: Jaunmuktane
authors.forename: J L
authors.initials: JL
authors.lastname: Holton
authors.forename: J M
authors.initials: JM
authors.lastname: Schott
authors.forename: D J
authors.initials: DJ
authors.lastname: Werring
authors.forename: P N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: M M
authors.initials: MM
authors.lastname: Reilly
mesh_terms: D000328:Adult; D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D008578:Meninges / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D009549:Nigeria; D011392:Proline / Q000235:genetics
chemical_list: D011392:Proline; D007930:Leucine