G. Biasucci

Effect of hepatitis C genotype on mother-to-infant transmission of virus☆☆☆★★★

We evaluated vertical transmission of hepatitis C virus (HCV) in 37 pregnant women, 20 of whom also had human immunodeficiency virus (HIV) antibody. The HCV subtypes 1a and 3a were prevalent among pregnant women with HIV infection. Infection with HCV was transmitted from 30.7% of the 13 mothers with HCV ribonucleic acid (RNA) and HIV antibody and from 25% of the 8 with HCV RNA alone. No mother with HCV antibody but no HCV RNA transmitted HCV to her infant. Subtypes 1b and 3a seemed to be the most common HCV genotypes transmitted.

Meat allergy: II–Effects of food processing and enzymatic digestion on the allergenicity of bovine and ovine meats.

OBJECTIVES This study was designed to evaluate whether peptic treatment of BSA and OSA affects their allergenicity and to evaluate the effect of technological treatments of meat for infant feeding on the allergenicity of these proteins. SUBJECTS Twelve children (8 males and 14 females) suffering from atopic dermatitis (AD), aged 12 months to 4.33 years (mean age 2.21 +/- 1.05 years). STUDY DESIGN AND METHODS Children suffering from atopic dermatitis (AD), (AD), clinically reactive and SPT-positive to beef, underwent skin prick testing (SPT) and radioallergosorbent test (RAST) with BSA and OSA, before and after peptic treatment. They were tested also with commercially available homogenized bovine meat (HBM) and with freeze-dried bovine (FDBM) and ovine (FDOM) meats. Peptic digestion of BSA and OSA was carried out in a Dubnoffs water bath containing 0.05 mg/ml of pepsin. SPT and RAST were performed for 1 mg/ml of BSA and OSA digested 5 minutes, 2 hours and 4 hours with pepsin; homogenized bovine meat, and FDBM and FDOM. SPT results were expressed as diameters (in mm) of the wheal obtained after SPT; a diameter > or = 3 mm was considered as positive. RAST was considered positive for IgE values 5 > UI/ml. RESULTS SPT to native BSA and OSA were positive in all patients. Only 2 of the 12 children were SPT-positive to HBM, FDBM, and FDOM. After digestion, SPTs and were positive as follows: for BSA, 4/12 after 5 minutes peptic treatment, 2/12 after 2 hours and 2/12 after 4 hours; for OSA, 3/12 after 5 minutes peptic treatment, none after 2 and 4 hours. None of RASTs was positive after peptic attack. CONCLUSIONS Both proteolytic digestion and technological treatment reduced the allergenic potential of meat products.

Structure and mutation analysis of the glycogen storage disease type 1b gene

Glycogen storage disease (GSD) 1b is the deficiency of endoplasmic reticulum glucose‐6‐phosphate (G6P) transport. We here report the structure of the gene encoding a protein likely to be responsible for G6P transport, and its mapping to human chromosome 11q23.3. The gene is composed of nine exons spanning a genomic region of approximately 4 kb. Primers based on the genomic sequence were used in single strand conformation polymorphism (SSCP) analysis and mutations were found in six out of seven GSD 1b patients analysed.

Early breastfeeding is linked to higher intelligence quotient scores in dietary treated phenylketonuric children

Strict control of phenylalanine intake is the main dietary intervention for phenylketonuric children. Whether other dietary‐related factors improve the clinical outcome for treated phenylketonuric children in neurodevelopmental terms, however, remains unexplored. We retrospectively compared the intelligence quotient (IQ) score of 26 school‐age phenylketonuric children who were either breastfed or formula fed for 20‐40 days prior to dietary intervention. Children who had been breastfed as infants scored significantly better (IQ advantage of 14.0 points, p= 0.01) than children who had been formula fed. A 12.9 point advantage persisted also after adjusting for social and maternal education status (p= 0.02). In this sample of early treated term infants with phenylketonuria there was no association between 1Q scores and the age at treatment onset and plasma phenylalanine levels during treatment. We conclude that breastfeeding in the prediagnostic stage may help treated infants and children with phenylketonuria to improve neurodevelopmental performance.

Lipid status and fatty acid metabolism in phenylketonuria

SummaryOwing to dietary treatment, patients with phenylketonuria (PKU) are supplied with only small amounts of animal fats and show low blood cholesterol levels and a poor long-chain polyunsaturated fatty acid (LC-PUFA) status. Endogenous synthesis should compensate for the physiological need for cholesterol for growth, but supplementary exogenous LC-PUFA seems advisable. PKU infants could develop depletion of docosahexaenoic acid, fundamental for the functional development of the central nervous system. The availability of arachidonic acid from plasma in PKU has been found to be related to dietary compliance, and seems to influence the synthesis of arachidonate-derived eicosanoids. Trials of dietary supplementation of PKU patients with oils containing LC-PUFA are in progress, but the functional consequences of these supplementations need further investigation.

The effects of n-3 and n-6 polyunsaturated fatty acids on plasma lipids and fatty acids of treated phenylketonuric children

Dietary-treated phenylketonuric patients (PKUs) display low levels of long-chain polyunsaturated fatty acids (PUFA) in plasma lipids. In a 6-month clinical trial we observed a decrease of triglycerides and an increase of n-3 long-chain PUFA in plasma of PKUs supplemented with fish oil, while no major differences in respect to the baseline values were found in a group supplemented with blackcurrant oil. A more complete source of long-chain PUFA of both the n-6 and n-3 series should be investigated for dietary supplementation of PKU patients.

PAH deficiency in Italy: correlation of genotype with phenotype in the Sicilian population

SummaryThe results of the neonatal screening for phenylalanine hydroxylase (PAH) deficiency in Sicily show that its incidence is higher than previously reported for mainland Italians and that non-PKU HPA is in excess of classical and mild PKU. The latter finding suggests that a high number of non-PKU HPA mutations would occur in the Sicilian population compared to populations with an inverted PKU/non-PKU HPA ratio. Previous studies have identified 40 mutations accounting for the majority (98%) of mutant alleles underlying PAH deficiency in Sicily. In order to study the molecular basis of the distribution of PAH deficiency phenotypes in the Sicilian population, we have correlated 31 of those mutations with clinical and metabolic phenotypes in 12 mentally retarded patients, 14 treated patients with classic or mild PKU, and 13 subjects presenting the non-PKU HPA phenotype. The present study proposes a tentative classification for a large number (26) of PAH gene mutations which may represent an additional tool for establishing a differential diagnosis for PAH deficiency in the Sicilian population.

Prenatal Diagnosis of Atypical Phenylketonuria

Atypical phenylketonuria (PKU) is a group of very rare and severe diseases caused by tetrahydrobiopterin (BH4) deficiency (Niederwieser and Curtius, 1987). So far three inborn errors of metabolism are known to cause BH4 deficiency. defects in: GTP cyclohydrolase I (GTPCH); 6-pyruvoyl tetrahydropterin synthase (PPH4S); and dihydropteridine reductase (DHPR) (Blau, 1988). Recently a new form of atypical PKU with unusual 7-iso-biopterin excretion in the urine of patients was described (Curtius et al., 1988). Prenatal diagnosis of BH4 deficiency can be achieved mainly by measurement of pterin metabolites in amniotic fluid and of enzyme activities in cultured fluid cells and fetal blood (Blau et al., 1987).

Granulocyte-colony stimulating factor and erythropoietin therapy in children with human immunodeficiency virus infection.

To determine whether granulocyte-colony stimulating factor and erythropoietin are effective in the therapy of neutropenia and anaemia related to human immunodeficiency virus (HIV) infection and to anti-retroviral agents, we recruited 11 HIV-infected children (mean age 4 years 10 months). All the children were given granulocyte-colony stimulating factor at a dosage of 5 μ-g/kg twice or three times a week while erythropoietin was administered additionally to three patients at a dosage of 50 U/kg twice a week. Both agents were administered subcutaneously for at least 4 months. Leukocyte and neutrophil counts significantly increased during the treatment (after 1 month, P = 0.003 and P = 0.009, respectively). Erythropoietin prevented blood transfusions and increased haemoglobin levels in the three children treated. No side-effects were recorded during the administration of either agent. Granulocyte-colony stimulating factor and erythropoietin appear to be safe and useful agents in the management of HIV-infected children.

Clinical relevance of short-chain acyl-CoA dehydrogenase (SCAD) deficiency: Exploring the role of new variants including the first SCAD-disease-causing allele carrying a synonymous mutation

Short-chain acyl-coA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation caused by ACADS gene alterations. SCADD is a heterogeneous condition, sometimes considered to be solely a biochemical condition given that it has been associated with variable clinical phenotypes ranging from no symptoms or signs to metabolic decompensation occurring early in life. A reason for this variability is due to SCAD alterations, such as the common p.Gly209Ser, that confer a disease susceptibility state but require a complex multifactorial/polygenic condition to manifest clinically. Our study focuses on 12 SCADD patients carrying 11 new ACADS variants, with the purpose of defining genotype–phenotype correlations based on clinical data, metabolite evaluation, molecular analyses, and in silico functional analyses. Interestingly, we identified a synonymous variant, c.765G > T (p.Gly255Gly) that influences ACADS mRNA splicing accuracy. mRNA characterisation demonstrated that this variant leads to an aberrant splicing product, harbouring a premature stop codon. Molecular analysis and in silico tools are able to characterise ACADS variants, identifying the severe mutations and consequently indicating which patients could benefit from a long term follow- up. We also emphasise that synonymous mutations can be relevant features and potentially associated with SCADD.