Clinical characteristics in patients with hereditary amyloidosis with Glu54Gln transthyretin identified in the Romanian population

Abstract

Background: In Romania, 23 patients have been diagnosed with hereditary transthyretin amyloidosis (ATTRh), 18 of whom have the Glu54Gln mutation. This retrospective cohort included all patients with Glu54Gln-mutated ATTRh who were diagnosed in Romania from 2005 to 2018. Results: Of 18 patients, 10 were symptomatic, five were asymptomatic carriers and three died during the study. All originated from NorthEast Romania. Median age at symptom onset was 45 years; median age at death was 51 years. All patients had cardiac involvement, including changes in biomarkers (mean N-terminal-pro B-type natriuretic peptide: 2815.6 pg/ml), electrocardiography (15% atrial fibrillation, 38% atrioventricular block, 31% right bundle block), and echocardiography (mean interventricular septum: 16 mm, mean left ventricular ejection fraction: 49%). Scintigraphy showed myocardial radiotracer uptake in all patients. In addition, 92% of patients had polyneuropathy at diagnosis and 53% had carpal tunnel syndrome; 69% exhibited orthostatic hypotension and 31% suffered from diarrhea. No renal or liver involvement was observed. Conclusions: This is the largest Glu54Gln-mutated ATTRh cohort diagnosed to date, and to our knowledge the first describing this variant worldwide. Clinical features of this variant are early onset, neurological and cardiac involvement, aggressive disease progression and short survival. Early diagnosis and therapeutic intervention have potential to improve prognosis in ATTRh.

Current Challenges of Cardiac Amyloidosis Awareness among Romanian Cardiologists

“…In Romania, a specific mutation with regional distribution for ATTRv (Glu54Gln) was discovered a decade ago [ 31 ] and fully characterized more recently [ 32 ]. In the latest publication the authors stated 23 patients have been diagnosed with ATTRv in Romania, 18 of whom had the Glu54Gln mutation which is characterized by early disease onset, mixed phenotype (both cardiac and neurological involvement), aggressive disease progression and short survival [ 32 ]. Another important finding was that all these 18 patients have origins in the North-Eastern region of Romania (Suceava County) where a cluster of ATTRv patients has been identified [ 32 ].…”

“…In the latest publication the authors stated 23 patients have been diagnosed with ATTRv in Romania, 18 of whom had the Glu54Gln mutation which is characterized by early disease onset, mixed phenotype (both cardiac and neurological involvement), aggressive disease progression and short survival [ 32 ]. Another important finding was that all these 18 patients have origins in the North-Eastern region of Romania (Suceava County) where a cluster of ATTRv patients has been identified [ 32 ]. They also reported a prevalence of ATTRv of 1.02 per 1,000,000 people in the general Romanian population with 2.39 per 100,000 people in Suceava County and stated that prevalence of this disease in Romania is substantially underestimated due to several factors, including lack of access to or refusal to receive medical care and limited survival of these patients [ 32 ].…”

“…Another important finding was that all these 18 patients have origins in the North-Eastern region of Romania (Suceava County) where a cluster of ATTRv patients has been identified [ 32 ]. They also reported a prevalence of ATTRv of 1.02 per 1,000,000 people in the general Romanian population with 2.39 per 100,000 people in Suceava County and stated that prevalence of this disease in Romania is substantially underestimated due to several factors, including lack of access to or refusal to receive medical care and limited survival of these patients [ 32 ].…”

Current Challenges of Cardiac Amyloidosis Awareness Among Romanian Cardiologists

“…However, contrary to common belief, CA is no longer considered a rare disease. In Romania, a specific mutation with regional distribution for ATTRv (Glu54Gln) was discovered a decade ago [17] and fully characterized more recently [18]. Moreover, recent studies revealed that ATTRwt can even be considered a common disease, but its prevalence remains to be established.…”

Epigenomic profiles of African American Transthyretin Val122Ile carriers reveals putatively dysregulated amyloid mechanisms

“…These symptoms often are attributed to other population-prevalent cardiovascular risk factors resulting in underestimation of the clinical penetrance of the Val122Ile 6 . The estimated age of onset for non-cardiac precursor phenotypes for hereditary transthyretin amyloidosis is between 30 to 40 years of age 7 . In two retrospective studies, carpal tunnel syndrome preceded hereditary transthyretin amyloidosis diagnosis by 9-10 years 8,9 .…”