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alpha I/65 Hereditary elliptocytosis (HE) is due to the duplication of TTG codon 154 (leucine) of alpha-spectrin and is associated with a constant haplotype. It was encountered exclusively in African and American Blacks, and in North Africans. We assumed that it diffused from the Benin-Togo area to Northern Africa. We now report two South Italian families with alpha I/65 HE. The phenotype fully conformed to previous descriptions. The mode of transmission was dominant; however, the manifestations were more pronounced when the common, low expression level alpha V/41 allele occurred in trans to the alpha I/65 allele, also conforming to previous records. The mutation underlying alpha I/65 HE turned out to be, again, the duplication of TTG codon 154 and the associated haplotype was the same as that encountered previously (+-+; XbaI, PvuII, MspI). Thus, the alpha I/65 allele found in Italy must have been introduced from North Africa across the Sicilian channel and would ultimately have originated from the Benin-Togo area. It would witness the same migratory stream as that followed by the Benin type haemoglobin S allele, which is also present in Southern Italy.

Recently it has been clearly established that partial deficiency of spectrin (SP) evaluated by radioimmunoassay is a common feature of many different forms of hereditary spherocytosis (HS). In this paper the determination of SP density (spectrin/band 3 ratio) in 46 HS patients and in 50 normal controls is presented. The comparison between the membrane SP density of HS subjects and controls showed a statistically significant difference (P less than 0.0005). Moreover no overlap between normal and HS subjects was observed. Membrane spectrin/band 3 ratio has been found related to some clinical features: indeed patients with severe HS showed a smaller SP density than those with milder HS. Our results show that the evaluation of membrane SP density permits a prompt diagnosis of HS and avoids extensive and unnecessary studies for other anaemias.

We describe three Italian subjects from two unrelated families affected with isolated hereditary spherocytosis (HS) without other clinical abnormalities, associated with partial spectrin and ankyrin deficiency. In both families the propositus has normal biological parents, and thus appears to be the result of a new mutation; in one of them the disease is further transmitted in an autosomal dominant fashion. Cytogenetic analysis of the latter family excluded abnormalities of the short arm of chromosome 8. We speculate that in both kindreds ankyrin deficiency is the primary defect related to ankyrin gene mutation. Several pieces of evidence suggest that ankyrin deficiency is probably the most common molecular defect in HS. It is inherited in a, dominant manner and its clinical and biochemical expression is heterogenous.

Precise data on the incidence of transforming ras oncogenes in pediatric tumors and the correlations with the histopathological properties of the tumors are very limited. Additionally the presence of ras activation in medulloblastomas has not been investigated so far. Using a combination of techniques including in vitro gene amplification by polymerase chain reaction (PCR) and detection of single base mutations by sequence-specific oligonucleotides we studied N-ras activation (mutations at codon 12, 13, and 61) in 32 medulloblastomas. DNA was isolated from 20 microns sections of formalin-fixed paraffin-embedded tissue. Mutations were found in 3 out of 32 examined medulloblastomas. In all cases only mutations of codon 61 were found: two of three mutations were C to A mutations at position 1 of the codon 61 (leading to a substitution of a glutamine residue for a lysine) and one was A to T mutation at position 3 in the same codon (glutamine-histidine). Our results indicate 10% incidence N-ras mutation in medulloblastoma, higher than in other CNS tumors studied so far. The main advantages of the procedure described are its greatly improved sensitivity, the increased speed with which tumor samples can be analyzed, and the possibility of using paraffin-embedded sections to analyze various rare tumors in retrospect.

Glucose-6-phosphate dehydrogenase (G6PD, D-glucose 6-phosphate: NADP oxidoreductase, E.C. 1.1.1.49) activity and the percentage of G6PD deficient erythrocytes was determined in 50 girls heterozygous for G6PD deficiency, 25 of whom had had hyperbilirubinaemia at birth and 25 who had normal bilirubin levels. The enzymatic activity was 2.32 +/- 0.87 I.U./g Hb in the first group and 3.31 +/- 0.92 I.U./g Hb in the second group. The percentage of G6PD deficient erythrocytes was 54.1 +/- 15.3 and 65.3 +/- 14.0, respectively. The level of enzymatic activity exceeded 4 I.U./g Hb and the percentage of G6PD deficient cells fell below 40% in only one of the subjects who had developed hyperbilirubinaemia. Levels of enzymatic activity below 4 I.U./g Hb, or percentages of G6PD deficient erythrocytes higher than 40% can therefore be considered to be associated with a high risk of developing neonatal hyperbilirubinaemia. In our opinion, these babies should receive prophylactic treatment with phenobarbital, as do G6PD deficient Mediterranean males.

A dynamic electrocardiographic Holter monitoring study was performed in 32 healthy children (20 males and 12 females, age range 6-11 years old), without heart disease, according to clinical and noninvasive instrumental examination. We evaluated atrioventricular conduction time (PR), heart rate (HR), and QT interval patterns defining the range of normality of these electrocardiographic parameters. The PR interval ranged from 154 +/- 10 ms (mean +/- SD) for HR less than or equal to 60 to 102 +/- 12 ms for HR greater than or equal to 120 (range 85-180). The absolute mean HR was 87 +/- 10 beats/min (range 72-104), the minimum observed HR being 61 +/- 10 (range 51-79), the maximum 160 +/- 20 beats/min (range 129-186). Daytime mean HR gave a mean value of 93 +/- 10 (range 71-148), while during night hours it was 74 +/- 11 (range 54-98). The minimum QT interval averaged 261 +/- 10 ms for HR greater than 120 and the maximum 389 +/- 9 ms for HR less than or equal to 60; the corresponding mean value of QTc (i.e., QT corrected for HR) ranged from 388 +/- 8 for HR less than or equal to 60 beats/min to 403 +/- 14 ms for HR greater than 120 beats/min. The results of the present study provide data of normal children which can be readily compared against those of subjects in whom cardiac abnormalities are suspect or patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Salicylamide-glucuronide formation has been determined in 27 children who underwent a favism crisis, 25 parents, and in 25 normal children who served as controls. A highly significant mean lower glucuronide formation was observed in the favism group in respect to the controls. The difference between fabic children and their parents was significant, and between parents and controls there was no significant difference.

40 full-term newborn infants with erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were used for a study concerning the effectiveness of agar per os in preventing severe hyperbilirubinemia. 20 randomly selected neonates were given agar (1 g/kg/day) orally in 4 daily doses from their 1st to their 5th day of life. 20 infants were not treated and served as controls. Three exchange transfusions were performed in the experimental as well as in the control group. According to these results, agar does not seem to be effective in preventing severe hyperbilirubinemia, which frequently occurs in newborn infants with erythrocyte G-6-PD deficiency.

Hemolysis was studied in 40 G-6-PD-deficient newborn infants, half of whom had bilirubin blood levels within the normal range whereas the others, who were hyperbilirubinemic, underwent exchange transfusion. Hemoglobin, hematocrit, hemopexin and haptoglobin showed no or little differences between either of the two groups and the controls. The findings confirm the authors' assumption expressed elsewhere that this form of hyperbilirubinemia is not hemolytic in nature.

Hb A2 was determined in 50 subjects with erythrocyte G-6-PD deficiency who presented with hyperbilirubinemia in the neonatal period and in 100 non-hyperbilirubinemic G-6-PD deficient newborn infants, at the age of 12 months or more. Six subjects in the first group and 13 in the second were found to be carriers of the beta-thalassemia trait. Statistical analysis of the data did not show any significant difference between the two groups. It seems that the beta-thalassemia trait does not provide any protection against neonatal hyperbilirubinemia associated with G-6-PD deficiency.

Glucose 6-phosphate dehydrogenase (G6PD) activity was assayed quantitatively in red cells from 100 consecutive G6PD-deficient newborn male babies born in a city hospital in Sassari, Sardinia. In four cases G6PD activity was between 30% and 45% of normal: these appeared on electrophoresis to be identical with G6PD Seattle-like. In 65 cases G6PD activity ranged from 2% to 14% of normal, while in the remaining 31 samples no activity could be detected in crude hemolysates. G6PD was partiall purified from 39 samples having activity below 14% of normal (including 20 with zero activity). G6PD activity could now be determined in all, and it was fully characterized in nine samples. These were shown to belong to two distinct classes on grounds of the Michaelis constant for glucose 6-phosphate and the elution profile from DEAE-Sephadex columns. These properties were compared with those of G6PD-deficient samples from Greece and from Israel. We conclude that there are at least three polymorphic G6PD-deficient variants in Northern Sardinia: G6PD Seattle-like, G6PD Mediterranean, and a new variant, which we designate G6PD Sassari. The GdMediterranean and GdSassari genes have been shown to breed true in family studies. We also produce evidence that the definition of G6PD Mediterranean must be carefully reassessed.

Salicylamide glucuronide formation has been studied in 23 newborn babies with erythrocyte G-6-PD deficiency and in 15 normal newborns on the first day of life. Glucuronide formation was significantly lower (p less than 0.001) in the former in comparison with the controls. In the newborns with G-6-PD deficiency who subsequently became hyperbilirubinemic an even lower mean glucuronide formation was observed (p less than 0.01) in respect to the non-jaundiced G-6-PD-deficient newborns.

We have investigated the association of neonatal jaundice (NNJ) and G6PD deficiency in consecutive births in a Northern Sardinian hospital. After excluding known causes for NNJ, and after correcting for the incidence of NNJ from unknown causes, we estimated that 20% of G6PD deficient male newborns develop NNJ resulting from their enzyme deficiency. By analyzing in detail 100 G6PD deficient babies we found no differences in birth weight or haemoglobin level between those without and those with NNJ, four of whom required exchange transfusion. We further showed by an accurate quantitative method that the residual G6PD enzyme activity was not significantly lower in G6PD deficient babies with NNJ compared to G6PD deficient babies without NNJ.

Phototherapy was employed in treatment of newborn infants with erythrocyte G-6-PD deficiency whose serum bilirubin concentrations exceeded 10 mg/100 ml on the second or third day of life. Exchange transfusions were required for two of the 12 treated babies and for six of the 12 control infants. It is noteworthy that exposure to light did not affect the erythrocyte GSH content nor did it increase hemolysis.

Glucose-6-phosphate dehydrogenase (G6PD) electrophoretic phenotype was determined in red cells from 979 male subjects born in Naples (Southern Italy). In 0.7% of the cases no activity could be detected in haemolysates, while in 1.3% of the cases G6PD activity was approximately 20% of normal and electrophoretic mobility was altered. Moreover in two subjects a G6PD with altered mobility and normal activity was shown. G6PD was characterized in 10 subjects with variant phenotype. We conclude that the G6PD(-) phenotype in the population of Naples consists of at least six different G6PD variants associated with mild deficiency and at least one, G6PD Mediterranean, associated with severe deficiency.