Neonatal screening for biotinidase deficiency: A 30-year single center experience

We reviewed the outcome of newborn screening for biotinidase deficiency performed at our department since 1987. Among 1,097,894 newborns screened, 461 were recalled, and 18 were identified as affected by complete or partial biotinidase deficiency (incidence 1:61,000, false positive rate 0.04%). The common missense mutation Q456H was found in 80% of patients with profound biotinidase deficiency. Of them, one patient harbored the novel mutation M399I in compound heterozygosity (M399I/Q456H). The complex allele A171T/D444H in cis was found in two patients with profound biotinidase deficiency (in homozygosity and in compound heterozygosity with the R211H mutation, respectively) and in one patient with partial biotinidase deficiency (in compound heterozygosity with the protective allele D444H in trans). All detected patients were treated and followed up at our Center until present. Biotin therapy (10–20 mg/day) allowed the full prevention of clinical symptoms in all patients with no adverse effects. These excellent outcomes confirm that newborn screening for biotinidase deficiency is a very effective secondary prevention program

Screening for later-onset Pompe's disease in patients with paucisymptomatic hyperCKemia.

Pompe's disease is an inherited metabolic myopathy caused by acid α-glucosidase deficiency. Early diagnosis optimizes the treatment effectiveness.Journal Articleinfo:eu-repo/semantics/publishe

High Incidence of Later-Onset Fabry Disease Revealed by Newborn Screening

The classic phenotype of Fabry disease, X-linked α-galactosidase A (α-Gal A) deficiency, has an estimated incidence of ∼1 in 50,000 males. The recent recognition of later-onset variants suggested that this treatable lysosomal disease is more frequent. To determine the disease incidence, we undertook newborn screening by assaying the α-Gal A activity in blood spots from 37,104 consecutive Italian male neonates. Enzyme-deficient infants were retested, and “doubly screened-positive” infants and their relatives were diagnostically confirmed by enzyme and mutation analyses. Twelve (0.03%) neonates had deficient α-Gal A activities and specific mutations, including four novel missense mutations (M51I, E66G, A73V, and R118C), three missense mutations (F113L, A143T, and N215S) identified previously in later-onset patients, and one splicing defect (IVS5(+1G→T)) reported in a patient with the classic phenotype. Molecular modeling and in vitro overexpression of the missense mutations demonstrated structures and residual activities, which were rescued/enhanced by an α-Gal A–specific pharmacologic chaperone, consistent with mutations that cause the later-onset phenotype. Family studies revealed undiagnosed Fabry disease in affected individuals. In this population, the incidence of α-Gal A deficiency was 1 in ∼3,100, with an 11:1 ratio of patients with the later-onset:classic phenotypes. If only known disease-causing mutations were included, the incidence would be 1 in ∼4,600, with a 7:1 ratio of patients with the later-onset:classic phenotypes. These results suggest that the later-onset phenotype of Fabry disease is underdiagnosed among males with cardiac, cerebrovascular, and/or renal disease. Recognition of these patients would permit family screening and earlier therapeutic intervention. However, the higher incidence of the later-onset phenotype in patients raises ethical issues related to when screening should be performed—in the neonatal period or at early maturity, perhaps in conjunction with screening for other treatable adult-onset disorders

Daily Fructose Traces Intake and Liver Injury in Children with Hereditary Fructose Intolerance

Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI