Inborn errors of metabolism in the Italian pediatric population: A national retrospective survey

Objective: To estimate at the national level the overall and disease-specific incidence of inborn errors of metabolism not mass screened at birth. Study design: Prospective nonconcurrent study (1985-1997) on patients 0 to 17 years of age, diagnosed in 23 Italian pediatric reference centers. Results: Cases (n = 1935) were recruited representing an incidence of 1:3707 live births for ∼200 diseases. In the last 5 years the incidence was 1:2758, reflecting improved diagnostic facilities, better coverage, increased medical awareness, and newly discovered diseases. In this period, the most frequent classes of diseases were lysosomal storage disease, 1:8275; disorders of carbohydrate metabolism, 1:19,532; organic acidopathies, 1:21,422; and primary lactic acidemias, 1:27,106. The most frequent individual diseases were Gaucher type I, 1:40,247; glycogenosis type 1a, 1:57,746; methylmalonic acidurias, 1:61,775; and ornithine transcarbamylase deficiency, 1:69,904. The incidence of diseases potentially identifiable with the use of a new neonatal mass screening technique is 1:6200. Of surviving patients, 11% reached adulthood by the end of the study. Conclusions: Inborn errors of metabolism constitute a highly heterogeneous category of rare diseases, representing a relevant cause of morbidity and mortality in childhood. This study quantifies the minimum size of the disease burden, providing useful tools for public health and health policy planning.