M O Kovalchuk

Bio: M O Kovalchuk is an academic researcher. The author has contributed to research in topics: Transthyretin & Proband. The author has an hindex of 1, co-authored 1 publications receiving 33 citations.

Familial transthyretin amyloidosis

Abstract: A case of familial transthyretin amyloidosis with TTR Cys 114 gene polymorphism is described (first in Russia and third in the world). The clinical picture of the proband was dominated by symptoms of autonomous polyneuropathy (orthostatic hypotension, erectile dysfunction, diarrhea, tachycardia, foot dyshydrosis) and of somatic nerve lesions (dumbness, impaired surface and deep sensitivity in the limbs). The patient presented with vitreous body opacity, disturbed eye movements, lateralized sensory symptoms, and difficulty of speech (baryphonia). Electromyographic quantitative autonomous testing and measurement of evoked sympathetic skin potentials confirmed affection of peripheral nerves. Heart ultrasound revealed restrictive amyloid cardiopathy. Histological analysis showed amyloid deposition in the intestines and sural nerve. The proband, his daughter, brother (monozygous twin), and brother's daughter had mutant TTR Cys 114 gene. The brother also had amyloid deposits in the absence of clinical signs of the disease. Analysis of familial medical history demonstrated autosomal dominant inheritance of this mutation in 4 generations. Its possible origin and clinical features of the disease are discussed.

First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy

Abstract: Purpose of review Early and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with id ...

Cardiac amyloidosis: An update on diagnosis and treatment.

Abstract: Cardiac amyloidosis (CA), once thought to be a rare disease, is increasingly recognized due to enhanced clinical awareness and better diagnostic imaging. CA is becoming of heightened interest to the cardiology community given more effective treatment strategies for light chain amyloidosis (AL), as well as emerging therapies for transthyretin amyloidosis (ATTR). Furthermore, reversing amyloid deposition in affected organs using monoclonal antibodies is actively being tested in clinical trials. A high index of suspicion and a systematic approach to the diagnosis of CA can lead to referral to a center of expertise for timely treatment.

Transthyretin: a multifaceted protein.

Abstract: Transthyretin is a highly conserved homotetrameric protein, mainly synthetized by the liver and the choroid plexus of brain. The carrier role of TTR is well-known; however, many other functions have emerged, namely in the nervous system. Behavior, cognition, neuropeptide amidation, neurogenesis, nerve regeneration, axonal growth and 14-3-3ζ metabolism are some of the processes where TTR has an important role. TTR aggregates are responsible for many amyloidosis such as familial amyloidotic polyneuropathy and cardiomyopathy. Normal TTR can also aggregate and deposit in the heart of old people and in preeclampsia placental tissue. Differences in TTR levels have been found in several neuropathologies, but its neuroprotective role, until now, was described in ischemia and Alzheimer's disease. The aim of this review is to stress the relevance of TTR, besides its well-known role on transport of thyroxine and retinol-binding protein.

Diagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: red-flag symptom clusters and treatment algorithm

Abstract: Hereditary ATTR (ATTRm) amyloidosis (also called transthyretin-type familial amyloid polyneuropathy [ATTR-FAP]) is an autosomal-dominant, adult-onset, rare systemic disorder predominantly characterized by irreversible, progressive, and persistent peripheral nerve damage. TTR gene mutations (e.g. replacement of valine with methionine at position 30 [Val30Met (p.Val50Met)]) lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, which form amyloid fibrils that deposit in peripheral nerves and various organs, giving rise to peripheral and autonomic neuropathy and several non-disease specific symptoms. Phenotypic and genetic variability and non–disease-specific symptoms often delay diagnosis and lead to misdiagnosis. Red-flag symptom clusters simplify diagnosis globally. However, in Japan, types of TTR variants, age of onset, penetrance, and clinical symptoms of Val30Met are more varied than in other countries. Hence, development of a Japan-specific red-flag symptom cluster is warranted. Presence of progressive peripheral sensory-motor polyneuropathy and ≥1 red-flag sign/symptom (e.g. family history, autonomic dysfunction, cardiac involvement, carpal tunnel syndrome, gastrointestinal disturbances, unexplained weight loss, and immunotherapy resistance) suggests ATTR-FAP. Outside of Japan, pharmacotherapeutic options are first-line therapy. However, because of positive outcomes (better life expectancy and higher survival rates) with living donor transplant in Japan, liver transplantation remains first-line treatment, necessitating a Japan-specific treatment algorithm. Herein, we present a consolidated review of the ATTR-FAP Val30Met landscape in Japan and summarize findings from a medical advisory board meeting held in Tokyo on 18th August 2016, at which a Japan-specific ATTR-FAP red-flag symptom cluster and treatment algorithm was developed. Beside liver transplantation, a TTR-stabilizing agent (e.g. tafamidis) is a treatment option. Early diagnosis and timely treatment using the Japan-specific red-flag symptom cluster and treatment algorithm might help guide clinicians regarding apt and judicious use of available treatment modalities.