TABLE 1.
Mutations Reported Associated With Leptomeningeal Amyloidosis
| Amino Acid Change (Mature Protein) Nucleotide Change | Cases Refs | Countries | Age of Onset (y) | Disease Duration (y) | CNS Neurological Symptoms | Autonomic Neuropathy | Peripheral Neuropathy | Hearing Loss | Visual Loss | Cardiac Dysfunction | CNS Protein | Neuroimaging |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| p.D38G (D18G) c.113A>G | 13 our case8,12,15,18 | Hungary, Japan, USA, China | 35.9±8.5 | 16.7±10.6 | Cognitive impairment, headache, ataxia, stroke, SAH | + | − | + | + | − | High | Leptomeningeal enhancement superficial siderosis |
| p.L32P (L12P) c.95T>C | 428–31 | UK, Nigeria, Germany | 36.1±6.0 | 15 | Cognitive impairment, headache, ataxia, stroke, seizures, SAH | + | + | + | − | + | High | Leptomeningeal enhancement |
| p.A45T (A25T) c.133G>A | 316,21,32 | Japan, Spain | 46.0±4.4 | 7.5±4.9 | Cognitive impairment, ataxia, stroke, seizures, SAH | − | + | + | − | − | High | Leptomeningeal enhancement, superficial siderosis |
| p.V50G (V30G) c.148G>A | 77,33,34 | USA, Germany | 46.1±8.9 | 5.6±3.6 | Cognitive impairment, headache, ataxia, stroke, seizures | − | − | − | + | − | High | Leptomeningeal enhancement |
| p.V50M (V30M) C.148G>A | 1117,35 | Mexico, Japan | 56.5±4.3 | — | Headache, seizures, hydrocephalus | + | + | − | − | − | High | Leptomeningeal enhancement Hydrocephalus |
| p.A56P (A36P) c.166G>C | 336 | Italy | 38±1.7 | 17.5±20.5 | Cognitive impairment, ataxia, stroke | − | + | + | + | − | High | Leptomeningeal enhancement Hydrocephalus |
| p.F64S F44S c.191T>C | 137 | USA | 26 | — | Cognitive impairment, headache | + | + | + | − | + | — | Leptomeningeal enhancement |
| p.T69P T49P c.205A>C | 119 | Ireland | 53 | — | Cognitive impairment, headache, seizures | − | + | − | − | + | High | Leptomeningeal enhancement |
| p.G73R G53R c.217G>A | 238 | USA | 51.0±7.1 | 17 | Cognitive impairment, stroke, seizures, hydrocephalus | − | − | − | − | − | — | Leptomeningeal enhancement Hydrocephalus |
| p.G73E G53E c.218G>A | 314 | France | 38.3±3.2 | 4.5±3.5 | Cognitive impairment, ataxia, headache, SAH | + | − | − | − | + | High | Leptomeningeal enhancement |
| p.G73A G53A c.218G>C | 113 | UK | 40 | — | Cognitive impairment, ataxia, stroke | − | + | − | − | + | High | Leptomeningeal enhancement |
| p.F84S F64S c.215T>C | 339,40 | Canada | 28 | 12 | Cognitive impairment, headache, ataxia, stroke, seizures, hydrocephalus | + | + | + | + | + | — | Leptomeningeal enhancement |
| p.Y89H Y69H c.265T>C | 139,41–43 | USA, Sweden, Canada | 50.4±9.2 | 7.7±3.1 | Cognitive impairment, headache, ataxia, stroke, seizures, SAH | − | + | + | + | − | High | Leptomeningeal enhancement |
| p.I127M I107M c.381T>C | 144 | Canada | 51 | — | Ataxia | + | + | − | − | + | High | — |
| p.Y134C Y114C c.401A>G | 66 | Japan | — | — | Cognitive impairment | + | + | + | − | + | — | Leptomeningeal enhancement |
CNS indicates central nervous system; SAH, subarachnoid hemorrhage.