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