Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy.

Abstract

OBJECTIVE:

To elucidate early skin denervation in hereditary transthyretin (TTR) amyloidosis and iatrogenic TTR amyloidosis.

METHODS:

We investigated intraepidermal nerve fiber density (IENFD) and clinical findings in 32 patients with hereditary TTR amyloidosis, 11 asymptomatic mutation carriers, 6 patients with iatrogenic TTR amyloidosis, and 23 healthy volunteers.

RESULTS:

IENFD values were reduced in patients with the V30M mutation (1.9 ± 2.1 per 1 mm), patients with non-V30M mutations (5.8 ± 3.2 per 1 mm), and patients with iatrogenic TTR amyloidosis (3.5 ± 1.8 per 1 mm) compared with healthy volunteers (11.8 ± 3.2 per 1 mm) (p < 0.01). Skin denervation also occurred, even in presymptomatic V30M mutation carriers (5.0 ± 2.2 per 1 mm). The IENFD was correlated with disease duration (ρ = -0.533, p = 0.002) and various peripheral neuropathy parameters such as sensory impairment in the Kumamoto clinical score (ρ = -0.575, p = 0.001), heat-pain detection threshold (ρ = -0.704, p < 0.001), and sural sensory nerve action potential (ρ = 0.481, p = 0.005). TTR amyloid deposits frequently occurred in connective tissues and vessels of the dermal reticular layer in patients with hereditary TTR amyloidosis and those with iatrogenic TTR amyloidosis.

CONCLUSIONS:

Patients with hereditary TTR amyloidosis and those with iatrogenic TTR amyloidosis may show early skin denervation even in the presymptomatic stage. IENFD may thus be useful for early diagnosis and may serve as a biomarker in clinical trials for hereditary and iatrogenic TTR amyloidosis.

• Authors: Teruaki Masuda, Mitsuharu Ueda, Genki Suenaga, Yohei Misumi, Masayoshi Tasaki, Ayane Izaki, Yukako Yanagisawa, Yasuteru Inoue, Hiroaki Motokawa, Sayaka Matsumoto, Mayumi Mizukami, Aiko Arimura, Takahisa Deguchi, Yoshihiko Nishio, Taro Yamashita, Yukihiro Inomata, Konen Obayashi, Yukio Ando
• Journal: Neurology (Neurology) Vol. 88 Issue 23 Pg. 2192-2197 (Jun 06 2017) ISSN: 1526-632X [Electronic] United States
• PMID: 28490654 (Publication Type: Journal Article)
• Copyright: © 2017 American Academy of Neurology.

Chemical References

• Prealbumin

Topics

• Adult
• Amyloid Neuropathies (pathology)
• Amyloid Neuropathies, Familial (pathology)
• Early Diagnosis
• Female
• Heterozygote
• Humans
• Iatrogenic Disease
• Male
• Middle Aged
• Mutation
• Prealbumin (genetics)
• Prodromal Symptoms
• Severity of Illness Index
• Skin (innervation, pathology)