Peroxisomal disorders - incidences in Sweden

Incidence calculations are crucial for understanding rare disorders, improving healthcare, and public health planning. Our study presents the incidence of peroxisomal disorders in Sweden. All patients diagnosed between 1985 and 2024 at the two existing laboratories, which determine very long-chain fatty acids (VLCFA), phytanic, pristanic, and L-pipecolic acid in plasma, and plasmalogens in erythrocytes, were included in the study. Specifically, the incidence of X-linked adrenoleukodystrophy (X-ALD) is essential for evaluating its inclusion in the national neonatal screening for inborn diseases. Since the incidence of these disorders remained almost constant over the last 20 years of the study, these data were used for calculations. The incidence for the entire cohort (2005-2024) was 1:29,100, excluding female carriers of X-ALD. The most common subgroup was hemizygous X-ALD, with an incidence of 1:65,100, followed by peroxisomal biogenesis disorders (PBDs; Zellweger spectrum disorders) at 1:73,800. These incidences align with other estimates for clinically detected patients, but not for X-ALD detected through neonatal screening, where the incidence is at least three times higher. This discrepancy is partly explained by the discovery of genetic variants of uncertain significance. Over the years, the age at diagnosis and survival time for PBDs have increased, indicating heightened awareness of attenuated forms and improved supportive treatment.