Fabry disease is a rare, X-linked inborn error of
glycosphingolipid catabolism caused by a deficiency in the activity of the lysosomal
enzyme,
alpha-galactosidase A. In affected patients, the
enzyme substrate,
globotriaosylceramide (Gb3), accumulates in cells of various tissues and organs. Lysosomal accumulation of Gb3 begins in utero, and signs and symptoms of
Fabry disease emerge in childhood and adolescence. The earliest presenting symptoms are typically
neuropathic pain and gastrointestinal problems, which can have a substantial impact on health-related quality of life. Life-threatening major organ involvement is rare in young patients, but signs of kidney dysfunction (e.g.,
proteinuria),
left ventricular hypertrophy, and
stroke have been reported in children. There are two
enzyme preparations for
therapy:
agalsidase alfa and beta. In two clinical trials of
enzyme replacement therapy (ERT) with
agalsidase alfa, including 37 children, boys demonstrated reductions in plasma Gb3 levels, and both boys and girls reported reductions in
neuropathic pain and in the use of
neuropathic pain medications. Heart rate variability, which is reduced in boys with
Fabry disease, was statistically significantly improved with 6 months of
agalsidase alfa treatment. In a single clinical study of
agalsidase beta in children (n =16), skin Gb3 deposits and plasma Gb3 levels were reduced in boys. Differences exist in the administration and the safety profile of these two
enzyme formulations. Follow-up of these cohorts and additional studies will be necessary to fully evaluate long-term efficacy of ERT in children with
Fabry disease.