Pathophysiology, Functional Assessment and Prognostic Implications of Nutritional Disorders in Systemic Amyloidosis.

Gastrointestinal involvement is a common clinical feature of patients with systemic amyloidosis. This condition is responsible for invalidating gastrointestinal symptoms, a significant macro and micronutrient deficit, and is a marker of disease severity. Gastrointestinal involvement should be actively sought in patients with systemic amyloidosis, while its diagnosis is challenging in patients with isolated gastrointestinal symptoms. The nutritional status in systemic amyloidosis plays an essential role in the clinical course and is considered a significant prognostic factor. However, the definition of nutritional status is still challenging due to the lack of internationally accepted thresholds for anthropometric and biochemical variables, especially in specific populations such as those with systemic amyloidosis. This review aims to elucidate the fundamental steps for nutritional assessment by using clinical and instrumental tools for better prognostic stratification and patient management regarding quality of life and outcomes.

An Overview of Molecular Mechanisms in Fabry Disease.

Fabry disease (FD) (OMIM #301500) is a rare genetic lysosomal storage disorder (LSD). LSDs are characterized by inappropriate lipid accumulation in lysosomes due to specific enzyme deficiencies. In FD, the defective enzyme is α-galactosidase A (α-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death. The increasing understanding of FD, and LSD in general, has led in recent years to the introduction of enzyme replacement therapy (ERT), which aims to slow, if not halt, the progression of the metabolic disorder. In this review, we provide an overview of the main features of FD, focusing on its molecular mechanism and the role of biomarkers.

Diagnosis and Management of Cardiovascular Involvement in Fabry Disease.

Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disease caused by pathogenic variants in the GLA gene. Cardiac involvement is common in FD and is responsible for impaired quality of life and premature death. The classic cardiac involvement is a nonobstructive form of hypertrophic cardiomyopathy, usually manifesting as concentric left ventricular hypertrophy, with subsequent arrhythmogenic intramural fibrosis. Treatment of patients with FD should be directed to prevent the disease progression to irreversible organ damage and organ failure. The aim of this review is to describe the current state of knowledge regarding cardiovascular involvement in FD, focusing on clinical and instrumental features, cardiovascular management, and targeted therapy.

The Role of New Imaging Technologies in the Diagnosis of Cardiac Amyloidosis.

Cardiac amyloidosis is an infiltrative disorder caused by transthyretin or immunoglobulin free light-chain deposition, which determines clinical disease with similar phenotype but different time course, prognosis and therapy. Multimodality imaging is the cornerstone for disease diagnosis and management. Multimodality imaging has revolutionized the approach to the disease favoring its awareness and simplifying its diagnosis, especially in ATTR cardiac amyloidosis. This describes the different imaging tools, from the traditional to the more novel ones, and highlights the different approach in each different setting (prognosis, subtyping, prognosis, monitoring disease progression, and response to therapy).