Gian Franco Meloni

A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes.

We report that a single-nucleotide polymorphism (SNP) in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1 diabetes mellitus (T1D). The variants encoded by the two alleles, 1858C and 1858T, differ in a crucial amino acid residue involved in association of LYP with the negative regulatory kinase Csk. Unlike the variant encoded by the more common allele 1858C, the variant associated with T1D does not bind Csk.

Favism in a female newborn infant whose mother ingested fava beans before delivery

We describe a case of favism in a female newborn infant with glucose-6-phosphate dehydrogenase (G6PD) deficiency whose mother had ingested fava beans 5 days before delivery. At birth there were clinical and hematologic signs of hemolytic anemia, hemoglobinuria, and no blood group immunization. Study of the G6PD activity and 2-deoxy-glucose-6-phosphate utilization rate revealed that the infant and the mother were heterozygous for G6PD deficiency.

Marked decline of favism after neonatal glucose-6-phosphate dehydrogenase screening and health education: the Northern Sardinian experience

Favism is a potentially fatal manifestation of glucose-6-phosphate dehydrogenase (G6PD) deficiency, and it is therefore a public health problem in areas where this genetic abnormality is common. In the district of Sassari (northern Sardinia), the frequency of G6PD male hemizygotes is approximately 7.5%, and therefore all newborns since 1971 have been screened for G6PD deficiency. We have analyzed the incidence of favism in this community in two 10-year periods: (1) 1961-1970; and (2) 1981-1990. In period 1, there were 508 cases of favism, of which 76% occurred in boys. In period (2) there were 144 cases of favism, of which only 52% in boys. Thus, between the two periods there was an overall decrease in the incidence of favism of 75%, whereas the proportion of girls affected has approximately doubled. These data suggest that neonatal screening and health education programs can produce a substantial decrease in the number of cases of favism, and that the relative increase in favism in girls is possibly due to failure of the screening method used to detect all the heterozygotes for G6PD deficiency.

Bilirubin levels in the acute hemolytic crisis of G6PD deficiency are related to Gilbert's syndrome

Abstract:  In this study we analyzed the effect of the (TA)7 polymorphism of the UGT1A gene associated with Gilberts syndrome in G6PD‐deficient subjects during an acute hemolytic crisis (tabic crisis). DNA from 44 subjects originating from the same geographic area in Sardinia was analyzed for the UGT1A promoter polymorphism. The increase of unconjugated bilirubin level during fabic crisis and its relationship with UGT1A polymorphism was evaluated. The UGT1A (TA)7 TATA box variant was found in 9/44 (21%) of the G6PD deficient subjects examined. The median value for unit of increase of bilirubin (mg/dl)/unit of decrease of hemoglobin (g/dl) was higher in variant homozygous than in heterozygous and normal subjects. These findings imply a contribution of the UGT1A polymorphism associated to Gilberts syndrome to development of the hyperbilirubinemia in G6PD deficient subjects during acute hemolytic anemia.

Glucose 6-phosphate dehydrogenase deficiency and cataract of patients in Northern Sardinia

We determined the activity level of glucose 6-phosphate dehydrogenase in 467 patients with cataract from northern Sardinia. Of 226 men, 18 (8%) had glucose 6-phosphate dehydrogenase deficiency. Of 241 women, 30 (12%) were heterozygous and two (1%) were homozygous for glucose 6-phosphate dehydrogenase deficiency. These prevalences were not significantly different from those expected in the general population. We concluded that patients with glucose 6-phosphate dehydrogenase deficiency do not have a higher risk of developing cataract.

Maternal-fetal interaction in the ABO system: a comparative analysis of healthy mothers and couples with recurrent spontaneous abortion suggests a protective effect of B incompatibility.

AbstractWe investigated the possible differential effects of A and B blood group materno-fetal incompatibility on human fertility through a comparative analysis of couples with recurrent spontaneous abortion (RSA) and healthy mothers. ABO phenotype was determined in 5180 healthy mothers and their newborn babies from the population of Sassari (Sardinia) and in 1359 healthy puerperae (women who have just given birth) from the population of Rome. Mother-newborn joint ABO distribution in healthy mothers was compared with wife-husband joint ABO distribution in RSA couples. Distortions from expected distribution were evaluated by symmetry analysis. In both RSA couples and healthy mothers significant deviation from expected symmetry patterns were observed. Deviations in RSA are in the opposite direction to those observed in healthy puerperae. The most important difference observed concerned the symmetric joint phenotypes mother (women) A / infant (husband) B (B incompatible) and mother (women) B / infant (husband) A (A incompatible). A low number of B incompatible in RSA couples and a high number of B incompatible in healthy mothers was observed. The phenomenon is much more evident in women aged 24-28 years, a period of maximum fecundity. It is possible that the presence of anti-B immunoglobulin in the mother might have a protective effect against fetal loss in some cases of mother-infant ABO incompatibility.

Glucose-6-phosphate dehydrogenase deficiency and bacterial infections in northern Sardinia

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Increased bilirubin production, ceruloplasmin concentrations and hyperbilirubinaemia in full-term newborn infants

Ceruloplasmin possesses antioxidant activity in vitro, but such a property has not been substantiated in vivo so far. However, it has been suggested that the lack of factors protective against oxidative haemolysis might have a role in neonatal hyperbilirubinaemia. Ceruloplasmin and alphafetoprotein concentrations were measured in cord blood in 78 unselected full-term singleton newborn infants without G6PD deficiency and haemolytic disease of the newborn; in the same infants, the carboxyhaemoglobin level was assessed on the fourth day of life and taken as an index of bilirubin production. The relationship between these variables and maximum bilirubin level in the first 4 days was studied by multiple regression analysis. High carboxyhaemoglobin levels and low ceruloplasmin concentrations, but not alphafetoprotein resulted, associated with hyperbilirubinaemia (P < 0.001). No relationship was found between carboxyhaemoglobin and ceruloplasmin levels. These results exclude an important role for ceruloplasmin in protecting against possible oxidative haemolysis in full-term newborn infants. Ceruloplasmin levels in cord blood are most probably related to hepatic metabolism and are better predictors of hyperbilirubinaemia than alphafetoprotein concentrations.

HbA1c levels in diabetic Sardinian patients with or without G6PD deficiency

Mgbodile and Onyeanusi [l] have recently reported that glycated hemoglogbin (HbA,) levels in glucose-6-phosphate dehydrogenase (G6PD)deficient Nigerians and in normal controls show no significant difference. These data contrast with those obtained by Baule et al. [2] in Sardinian subjects. The lower HbAr levels of G6PD-deficient subjects should, according to the latter, be taken into consideration in the management of G6PDdeficient diabetic patients. The present paper reports the results of a study aiming to evaluate HbA,, levels in diabetic Sardinian patients with or without G6PD-deficiency.

Bilirubin Levels in The Acute Hemolytic Crisis of G6PD Deficiency are Related to Gilberts Syndrome

In this study we analyzed the effect of the (TA)7 polymorphism of the UGT1A gene associated with Gilberts syndrome in G6PD-deficient subjects during an acute hemolytic crisis (fabic crisis). DNA from 44 subjects originating from the same geographic area in Sardinia was analyzed for the UGT1A promoter polymorphism. The increase of unconjugated bilirubin level during fabic crisis and its relationship with UGT1A polymorphism was evaluated. The UGT1A (TA)7 TATA box variant was found in 9/44 (21%) of the G6PD deficient subjects examined. The median value for unit of increase of bilirubin (mg/dl)/unit of decrease of hemoglobin (g/dl) was higher in variant homozygous than in heterozygous and normal subjects. These findings imply a contribution of the UGT1A polymorphism associated to Gilberts syndrome to development of the hyperbilirubinemia in G6PD deficient subjects during acute hemolytic anemia.