Transthyretin familial amyloid polyneuropathy (TTR‐FAP) in Mallorca: a comparison between late‐ and early‐onset disease

Abstract

The age of onset (AO) of hereditary ATTR amyloidosis (hATTR) is known to vary between populations, with differing characteristics reported according to AO in endemic/non‐endemic foci. This was a retrospective study of patients with early AO (<50 years) and late AO (≥50 years) hATTR at our center in Mallorca. Data were collected on patient demographics, clinical disease manifestation, and physical symptoms. A total of 95 patients were analyzed, with mean follow‐up of 9 years from diagnosis. The early AO group included 53 patients (33 male) and the late AO group included 42 patients (21 male). Neurologic involvement was the most common initial symptom, although it was significantly more frequent in the late AO vs. early AO group (p = 0.015). Autonomic involvement was observed in 26% of patients in the early AO group, but was rarely observed in the late AO group (5%). During follow up, cardiologic symptoms, renal involvement, and ophthalmologic symptoms were significantly more common in the late AO group (p < 0.05). This retrospective study demonstrates the variation in disease presentation and progression according to AO of hATTR at our Mallorcan center.

Real-world outcomes in non-endemic hereditary transthyretin amyloidosis with polyneuropathy: a 20-year German single-referral centre experience

“…The results of our study largely confirm a number of essential findings from previous studies conducted in other countries: Late-onset ATTRv-PN was found to be more difficult to diagnose and to be associated with higher neurologic disease severity and frequent cardiac involvement [19,21,27]. Muscle weakness and impairment of gait, both clinical indicators of advanced polyneuropathy, were also frequently met in our patient cohort.…”

“…However, most prospective studies on tafamidis have focussed on cohorts in endemic ATTRv-PN hotspots such as Portugal or Brazil recruiting mostly younger patients at early stages of the disease [11,12,18,19]. Meanwhile, patient cohorts in other parts of the world presenting with different genotypes and phenotypes are still underrepresented in the current literature [13,20].…”

“…Meanwhile, patient cohorts in other parts of the world presenting with different genotypes and phenotypes are still underrepresented in the current literature [13,20]. The share of late-onset ATTRv-PN patients in some European countries has been described to be as high as 44% in some retrospective studies and may be much higher than in the typical ATTRv amyloidosis hotspots [19]. These patients are known to experience disease progression at a faster rate, are more difficult to diagnose, or are diagnosed at later disease stages than patients with endemic ATTRv-PN [13].…”

Late-onset hereditary ATTR V30M amyloidosis with polyneuropathy: Characterization of Brazilian subjects from the THAOS registry

“…Val30Met (V30M) mutation is the most common mutation in the transthyretin gene worldwide, and the classical V30M ATTRv-PN phenotype is of a small-fiber predominant neuropathy with onset in third or fourth decade [1]. A late-onset form of V30M ATTRv-PN in which symptoms manifest in the sixth decade or later has been reported in several countries, and seems to be the most common form outside endemic regions [2][3][4][5][6]. Late-onset V30M ATTRv-PN affects both large and small sensory fibers and has few autonomic symptoms and more severe motor and cardiac involvement than earlyonset disease [7,8].…”

Anticipation on age at onset in kindreds with hereditary ATTRV30M amyloidosis from the Majorcan cluster

“…Variation in AO between clusters and within the same focus has already been described [15][16][17]. Additionally, mean age at onset (AO) varies between geographical areas such as Portugal, Japan, Sweden, Majorca and Brazil, although the range is similar: 19-82 in Portugal [18], 23-79 in Majorca [19]. Among Portuguese families, an increasing number of late-onset cases (!50 years) have been observed and asymptomatic carriers aged up to 95 years have been identified [16].…”