Lyso-Gb3 in a Fabry pediatric cohort diagnosed by newborn screening

Fabry disease (FD), an X-linked lysosomal storage disorder caused by the deficiency of α-galactosidase A, results in the accumulation of globotriaosylceramide and its deacylated derivative globotriaosylsphingosine (lyso-Gb3). Little is known about lyso-Gb3 levels in pediatric population identified through neonatal screening. This study evaluated levels of lyso-Gb3 at birth and during childhood.

Plasma lyso-Gb3 levels were monitored annually in 25 males with FD identified by newborn screening. Long-term clinical follow-up was extended up to a maximum of 9 years of age.

A total of 105 plasma samples were collected. For 14 patients with later-onset (LO) variants, 53 lyso-Gb3 values were collected, 50 of which were elevated (mean 2.87 nmol/L, SD 3.46, nv <0.43 nmol/L). We analyzed 52 samples from 11 patients with variants of uncertain significance (VUS), 29 of which were mildly elevated (0.43-1 nmol/L), with overlapping values at birth. Increased lyso-Gb3 levels for LO variants were most pronounced during the first 2 years, after which the values plateaued. Conversely, lyso-Gb3 in VUS increased minimally and then stabilized.

Lyso-Gb3 levels were elevated earlier than clinical symptoms in infants with LO FD, increased significantly in the first 2 years of life, and remained stable during follow-up. Differences in Lyso-Gb3 levels between LO variants and VUS were significant (P < .0001).