α-Fetoprotein assay on dried blood spot for hepatoblastoma screening in children with overgrowth-cancer predisposition syndromes

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Metabolic progression to clinical phenotype in classic Fabry disease

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder due to α-galactosidase A (α-Gal A) deficiency. Clinical onset of Fabry disease is preceded by significant storage of globotriaosylceramide (Gb3) and related glycosphingolipids, but the extent of the metabolic progression before symptoms is unknown. Using a newly recognized effector and marker of Fabry disease, globotriaosylsphingosine (LysoGb3), we aimed to provide a metabolic picture of classic Fabry disease from the neonatal period to childhood. METHODS: LysoGb3 was assessed at different times in two brothers with classic Fabry disease (genotype c. 370–2 A > G). The firstborn was diagnosed after clinical onset at 11 years of age, whereas the second-born was diagnosed in the neonatal period. LysoGb3 was measured in dried blood spots by high-sensitive electrospray ionization liquid chromatography tandem mass spectrometry. RESULTS: Blood LysoGb3 concentrations were consistent with patients’ age and clinical picture, with lower levels in the asymptomatic neonate (19.1 ng/ml) and higher levels in the symptomatic child (94.3 ng/ml). In the second-born, LysoGb3 doubled during the first 5 months of life (37.4 ng/ml), reaching ~40% concentration observed in the symptomatic period. The neonatal LysoGb3 concentration in classic Fabry disease exceeded that observed in normal subjects by over 15 times. CONCLUSIONS: A substantial increase of LysoGb3 was documented during the first months of life in classic Fabry disease, suggesting an early plateau during the pre-symptomatic period. Such a progressive metabolic trend during the pre-symptomatic period implies the potential definition of a metabolic threshold useful for a preventive therapeutic approach of classic Fabry disease. Additionally, the consistent increase of LysoGb3 in the neonatal period in classic Fabry disease suggests LysoGb3 as a useful marker for improving the specificity of newborn screening for Fabry disease

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

A Comprehensive Analysis of Body Mass Index Effect on in Vitro Fertilization Outcomes

The effect of a raised body mass index (BMI) on the outcome of assisted reproduction technology (ART) still represents a controversial issue. Even less clear is whether BMI acts with a potential detrimental effect on IVF outcomes via a deleterious effect on innate quality of oocytes or on the environmental milieu within the uterus. With the aim to better understand the mechanisms underlying the potential deleterious effect of an increased BMI on IVF outcomes, we have evaluated the effects of female BMI on number and quality of retrieved oocytes, fertilization rate, embryo score and incidences of ongoing pregnancy and live births among couples undergoing IVF in an Italian population. Data from 1602 women who underwent their first IVF cycle were retrospectively analyzed. A significantly reduced percentage of mature oocytes when comparing obese (BMI ≥ 30 kg/m2) and normal-weight patients (BMI = 18.50–24.99 kg/m2) was found. After adjusting for maternal age and other confounders, odds for ongoing pregnancy rate showed no differences across different BMI categories. However, a significant increased odds ratio (OR) could be observed for miscarriage rate in patients with BMI ≥ 25 (OR = 2.5; p = 0.04). These results should be taken into account in order to define optimal strategies for overweight and obese patients referring to ART procedures