ATTRv phenotypes
| . | ATTRv-PN . | ATTRv-CM . | ATTRv-LM or CNS . | ATTRv-O . | |
|---|---|---|---|---|---|
| Epidemiology | 10 000 | Main variant: V122I: 3.4% of African Americans 40 000 gene carriers Other variants in many countries | 82 cases reported (global) | Ubiquitary (dozens of families) | |
| No. of TTR variants | 100 | 24 | 15 | 5 | |
| Main variants | EO V30M | LO V30M, S77Y, E89Q, and I107V | V122I, T60A, I68L, and L111M | D18G, Y69H V30G, L12P, A25T, V30M, G53E, and Y114C | G83A, R34G, Y69H, K35T, and W41L |
| Age at onset, y | 31.9 ± 7.6 | 64.5 ± 6.5 | 74 ± 7 (rare before 50 y) | 44.9 ± 9.1 | 35-56 |
| Male sex, % | 50 | 86 | 80-85 | Unk | Unk |
| Ethnicity | Portuguese Japanese Brazilian Mallorcan Cypriot | Global | V122I: African Americans and Caribbean Other variants: clusters | Various | Various |
| Duration of symptoms at diagnosis (y) | 2 | 2.8 | 1 | Unk | Unk |
| Main clinical manifestations | Symptoms in the feet Autonomic symptoms Unexplained weight loss | Neuropathic (80%) Autonomic (10%) Cardiac (4%-20%) | Heart failure symptoms Fluid overload History of CTS 50% | Cognitive impairment Ataxia Headache Seizures Stroke SAH Hearing loss | Blurred vision Vitreous opacities Glaucoma |
| Penetrance | High 80% at 50 y | High 80% at 80 y | Low | ||
| Tools for diagnosis | TTR gene sequencing Skin biopsy and LSGB | TTR gene sequencing Skin biopsy and LSGB | TTR gene sequencing DPD scintigraphy | TTR gene sequencing MRI of the brain and spine PiB PET LM biopsy | TTR gene sequencing Vitreous amyloid deposit |
| Natural history | Time to walking with aid, 7 y | Time to walking with aid, 2.6 y | Terminal heart failure Cardiac arrhythmia | ||
| Survival from diagnosis, y | 10 | 4.7 | 2 to 3 | Unk | Unk |
| Survival from onset, y | 12 | 7.3 | 3 to 4 | 9.3 ± 7.1 | Unk |
| Cause of death | Cachexia Sudden death Sepsis | Heart failure Cachexia Secondary infection | Heart failure Sudden death Stroke | Stroke SAH Status epilepticus | |
| . | ATTRv-PN . | ATTRv-CM . | ATTRv-LM or CNS . | ATTRv-O . | |
|---|---|---|---|---|---|
| Epidemiology | 10 000 | Main variant: V122I: 3.4% of African Americans 40 000 gene carriers Other variants in many countries | 82 cases reported (global) | Ubiquitary (dozens of families) | |
| No. of TTR variants | 100 | 24 | 15 | 5 | |
| Main variants | EO V30M | LO V30M, S77Y, E89Q, and I107V | V122I, T60A, I68L, and L111M | D18G, Y69H V30G, L12P, A25T, V30M, G53E, and Y114C | G83A, R34G, Y69H, K35T, and W41L |
| Age at onset, y | 31.9 ± 7.6 | 64.5 ± 6.5 | 74 ± 7 (rare before 50 y) | 44.9 ± 9.1 | 35-56 |
| Male sex, % | 50 | 86 | 80-85 | Unk | Unk |
| Ethnicity | Portuguese Japanese Brazilian Mallorcan Cypriot | Global | V122I: African Americans and Caribbean Other variants: clusters | Various | Various |
| Duration of symptoms at diagnosis (y) | 2 | 2.8 | 1 | Unk | Unk |
| Main clinical manifestations | Symptoms in the feet Autonomic symptoms Unexplained weight loss | Neuropathic (80%) Autonomic (10%) Cardiac (4%-20%) | Heart failure symptoms Fluid overload History of CTS 50% | Cognitive impairment Ataxia Headache Seizures Stroke SAH Hearing loss | Blurred vision Vitreous opacities Glaucoma |
| Penetrance | High 80% at 50 y | High 80% at 80 y | Low | ||
| Tools for diagnosis | TTR gene sequencing Skin biopsy and LSGB | TTR gene sequencing Skin biopsy and LSGB | TTR gene sequencing DPD scintigraphy | TTR gene sequencing MRI of the brain and spine PiB PET LM biopsy | TTR gene sequencing Vitreous amyloid deposit |
| Natural history | Time to walking with aid, 7 y | Time to walking with aid, 2.6 y | Terminal heart failure Cardiac arrhythmia | ||
| Survival from diagnosis, y | 10 | 4.7 | 2 to 3 | Unk | Unk |
| Survival from onset, y | 12 | 7.3 | 3 to 4 | 9.3 ± 7.1 | Unk |
| Cause of death | Cachexia Sudden death Sepsis | Heart failure Cachexia Secondary infection | Heart failure Sudden death Stroke | Stroke SAH Status epilepticus | |
CTS, carpal tunnel syndrome; LM, leptomeningeal biopsy; LSGB, labial salivary gland biopsy; MRI, magnetic resonance imaging; PiB PET, Pittsburgh compound B (PiB)–PET; SAH, subarachnoid hemorrhage; Unk, unknown.