Fabry disease: Review and experience during newborn screening

Trends Cardiovasc Med. 2018 May;28(4):274-281. doi: 10.1016/j.tcm.2017.10.001. Epub 2017 Oct 20.


Fabry disease (FD) is an X-linked lysosomal storage disease and is the result of mutation in the α-Galactosidase A gene; such mutations cause a deficiency in α-Galactosidase A enzyme and an accumulation of glycosphingolipid in tissue. Affected males with classic FD have little or no enzyme activity and have an early onset of symptoms and signs, including acroparesthesias, hypohidrosis, angiokeratomas, gastrointestinal dysfunction and/or a characteristic corneal dystrophy during childhood/adolescence. Males with late-onset FD who have residual enzyme activity develop progressive multi-systemic involvement that leads to renal failure and hypertrophic cardiomyopathy, as well as cerebrovascular disease; these events mostly occur during the fourth to seventh decades of life. Heterozygous females can develop vital organ damage that in turn causes severe morbidity and mortality; these symptoms may be as severe as those in affected males. For the treatable disease, this review aims to raise awareness of early recognition and further management of FD based on newborn screening. As newborn screening for FD has been implemented worldwide, it allows the early detection of individuals with Fabry mutations. Based on screening studies, the prevalence of the later-onset type FD is much higher than that of classical type FD. Newborn screening studies have also revealed that patients with FD may develop insidious but ongoing irreversible organ damage. The timing of enzyme replacement therapy, which is able to stabilize the progression of disease, is important in order to prevent irreversible organ damage. Therapies that may become available in the future include pharmacological chaperones and substrate reduction therapy, both of which are still under investigation as ways of improving the health of individuals with FD.

Keywords: Cardiomyopathy; Enzyme replacement therapy; Fabry disease; Newborn screening.

Publication types

  • Review

MeSH terms

  • DNA Mutational Analysis*
  • Disease Progression
  • Enzyme Replacement Therapy
  • Fabry Disease / diagnosis*
  • Fabry Disease / drug therapy
  • Fabry Disease / enzymology
  • Fabry Disease / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Infant, Newborn
  • Male
  • Mutation*
  • Neonatal Screening / methods*
  • Phenotype
  • Predictive Value of Tests
  • Risk Factors
  • alpha-Galactosidase / genetics*
  • alpha-Galactosidase / therapeutic use


  • alpha-Galactosidase
  • alpha-galactosidase A, human

Supplementary concepts

  • Fabry Disease, Cardiac Variant