A review of Fabrys disease- pathophysiology, clinical presentation and treatments

Fabrys disease is a lysosomal storage disorder, caused due to mutation in the GLA gene in X-chromosome encoding for alpha galactosidase A enzyme. It’s a pan ethnic disorder with multisystem involvement. The reported prevalence of Fabrys is less but new-born screening shows higher values, indicating it is largely underestimated. It is inherited as X-linked dominant form. The hemizygous males manifests greater severity of symptoms and heterozygous females presents asymptomatic to severe symptoms. Pathophysiological changes occur due to insufficient breakdown of globotriosylceramide in lysosomes. Hence its accumulation causes dysfunction of cells, tissues and organ systems. The classic type 1 of Fabrys disease shows symptoms in childhood and late-onset type 2 shows later in life at around 30-40 years of age. The early symptoms are neuropathic pain, diarrhea, corneal verticellata, hypohydrosis, intolerance to heat and exercise followed by renal, cardiac and cerebrovascular involvement. The life expectancy and quality of life in Fabrys disease is considerably lesser than of that of general population. Rigorous new-born screening, detection in family members, early diagnosis and enzyme replacement and supportive management is important for slowing the progression of disease and decreases the morbidity and mortality, thus improving the overall well-being. There a is a need for awareness and education of physicians and patients about the disease with more research encouraged to develop newer and more efficient therapies for its management

Abstract 15760: Left Atrial Dysfunction in Patients With Anderson - Fabrys Disease Using Magnetic Resonance Imaging Derived Left Atrial Phasic Function

Background: Anderson-Fabrys disease (AFD) is an x-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase. This results in accumulation of globotriaosylceramide in various organs. The hallmark of cardiac involvement is left ventricular hypertrophy (LVH). However, autopsy studies have demonstrated involvement of the left atrium (LA) as well. There is currently limited data on left atrial volumes and function in patients with AFD. We sought to assess LA phasic volumes and function in patients with AFD using cardiac MRI (CMR) cine data. Method and Results: This was a retrospective study. Consecutive patients with clinically indicated CMR at our center were included. CMR acquired 2 and 4 chamber steady state free precession (SSFP) cine data were used to measure LA volume and phasic function with commercially available off-line software (eSieVVI, Siemens Medical System). We included 37 patients with AFD (18 males, mean age 48±13 yrs) and 22 age balanced healthy volunteers (8 males, mean age of 40±14 yrs). LA maximal and conduit volumes were not different between AFD and controls, but the LA minimal was larger (Table). Volume derived reservoir, conduit, and pump function were significantly reduced in AFD (Table). Strain measured reservoir and pump function were also significantly reduced in AFD. An inverse correlation was seen between LA reservoir strain and left ventricular (LV) mass (r=-0.53) and myocardial late gadolinium enhancement (LGE) measured using the 4 (r=-0.67) and 6 (r=-0.67) standard deviation thresholds. Conclusion: This is the first study to demonstrate abnormal LA function in patients with AFD using both volumetric and strain techniques. Patients with AFD had reduced LA reservoir and pump function with modest correlation with disease severity based on the burden of LV LGE and LV mass. Further studies are needed to assess the relationship between LA function and prognosis including the development of atrial arrhythmia.