Clinical and genetic study of a family with spinocerebellar ataxia type 1 (SCA1) and beta-thalassemia.

We report a family affected by autosomal dominant ataxia, in which numerous members also showed microcytosis. Genetic analysis demonstrated a CAG expansion in the SCA1 locus in five members, while all subjects with microcytosis revealed a C-T substitution at codon 39 of the beta-globin gene. A pure cerebellar syndrome with prominent gait ataxia characterized the first stages of the neurological disease. The fully developed disease included additional clinical findings such as dysarthria and dysphagia, and instrumental signs of axonal involvement of the peripheral nerves. Ophthalmoplegia was not observed. The coexistence of hereditary spinocerebellar degeneration and erythropathies or hemoglobinopathies has been previously described. We discuss the possible linkages between these two pathologies.

Pattern of iron excretion in relation to haemoglobin level and iron load in 8 haematological patients following the administration of subcutaneous deferrioxamine.

Iron excretion following subcutaneous administration of deferrioxamine (DFO) was measured between two transfusions of packed red cells in 6 patients with beta-thalassaemia major on the high level Hb transfusion regime; and in a single 3-day period in 2 other patients, 1 with transfused beta-thalassaemia major and the other with haemolytic anaemia due to PK deficiency. The pattern of iron excretion did not change significantly during the period between the two transfusions and was found to be related to serum ferritin levels. The proportion of iron excreted in the stools was inversely related to the serum ferritin level. These observations on iron excretion are of practical importance in relation to DFO administration, especially when evaluated in thalassaemics with normal haemoglobin levels and low iron stores.

A simple electrophoretic procedure for fetal diagnosis of beta-thalassaemia due to short deletions.

This study describes three couples at risk for homozygous beta-thalassaemia in which one of the partners carried a short deletion beta-thalassaemia defect. Detection of short deletions in trophoblast DNA was accomplished by the very simple procedure of non-denaturing polyacrylamide gel electrophoresis. This method may be applied to detect beta-thalassaemia mutations due to deletion or addition of more than two nucleotides.

[The prevention of beta-thalassemia homozygosity]. / La prevenzione dell'omozigosi beta-talassemica.

Theoretical and practical aspects of programs for prevention of homozygous beta-thalassaemia are discussed and data concerning their efficacy are presented. Prevention of the beta-thalassaemia homozygous state is feasible at a reasonable cost.

A new funipuncture technique: two-needle ultrasound- and needle biopsy-guided procedure.

A new technique is presented for funipuncture under ultrasound guidance using a biopsy guide and a 20/25-gauge needle combination. The 20-gauge needle was used for uterine entry and the 25-gauge needle for the actual cord puncture. The method was used for sampling fetal blood in 262 pregnancies with 264 fetuses (two sets of twins) between 17-39 weeks, at risk for beta-thalassemia, chromosomal disorders, TORCH infection, fetal hypoxia, and Rh-isoimmunization. Pure fetal blood was aspirated from 241 fetuses (91.3%), including the twins. The procedure lasted less than 5 minutes in 76.5% of the cases and less than 10 minutes in 90.1% of the cases. Intra-amniotic bleeding was seen in only 23.1% of the cases, and fetal bradycardia was not noted. Forty-four pregnancies were terminated after the diagnosis of genetic or infectious disease. Seven fetuses at risk for Rh-isoimmunization, found to be Rh-positive and anemic, were transfused immediately after blood sampling using the same needle. Of the 220 continuing pregnancies, there were 14 fetal losses (three before 28 weeks and 11 after 28 weeks or during the perinatal period). A probable etiology for the loss was found in 11 cases. These included one severely Rh-isoimmunized hydropic fetus who died in utero after transfusion at 26 weeks, one fetus who died in utero at 31 weeks following a car accident, and nine malformed newborns. The corrected rate for fetal losses probably related to the procedure was thus 0.9% before 28 weeks and 0.8% after 28 weeks. This new funipuncture technique seems to have several advantages over the freehand and/or biopsy-guided single-needle techniques.

Transabdominal chorionic villus sampling: analysis of 350 consecutive cases.

We report a series of 350 patients submitted to transabdominal chorionic villus sampling (CVS). A technique using two ultrasound-guided needles and a suction pump was used. In most cases, the procedure was performed between 9 and 13 weeks. Twenty-one pregnancies were selectively terminated; nine spontaneous abortions followed the procedure and one fetal loss after 28 weeks was recorded; 153 pregnancies are in progress and 169 delivered fetuses are alive and well. Transabdominal biopsy is a feasible and effective technique for CVS.

Haplotypes of thalassaemic families from the Po river delta: importance for prenatal diagnosis of beta-thalassaemia.

The beta globin haplotypes, corresponding to 50 normal and 50 thalassaemic chromosomes, were determined in 25 families from the Po river delta area who had beta thalassaemia. The haplotypes were obtained by studying the familial segregation of 6 restriction fragment length polymorphisms of the beta globin gene cluster. The results show an almost exclusive presence of 3 haplotypes linked to the beta thalassaemia chromosomes of this area: haplotype I, II and IX according to Orkin's classification. It is therefore possible that only two thalassaemic mutations are present. A wider variety of haplotypes was found to be linked to normal chromosomes. Prenatal diagnosis, by the analysis of polymorphic sites (the 6 plus one other) was possible in 92% of the cases. The probable high homogeneity of the molecular mutations makes the use of specific oligonucleotides practical and applicable to prenatal diagnosis.

Discrimination of type I from insulin-treated type II diabetic patients by C-peptide measurement.

Residual B-cell function was assessed in 61 type I and 17 type II insulin-treated diabetics by measuring plasma C-peptide concentration before and after i.v. injection of 1 mg glucagon to evaluate a possible difference in response to the test in the two groups. Fasting and post-stimulatory C-peptide levels were significantly higher in type II diabetics than in type I (0.45 +/- 0.25 vs 0.12 +/- 0.10 nmol/l for basal IRCP, 0.39 +/- 0.19 vs 0.06 +/- 0.11 nmol/l for delta IRCP, p less than 0.0001), but there was some overlap in individual values. Twenty-one percent of type I and 29% of type II diabetics had values in the overlap area. These percentages were reduced to 6% and 12%, respectively when only long-term (duration of diabetes more than five years) type I diabetics were considered. These data indicate that a glucagon test is useful to discriminate most type I diabetics from insulin-treated type II diabetics.

Erythropoietin levels in heterozygous alpha-thalassemia.

In guinea pig bone marrow cultures with heterozygous alpha-thalassemic serum, 59Fe uptake values are elevated above iron values of cultures with serum of normal subjects. These results show that erythropoietin (EP) activity values in heterozygous alpha-thalassemia are comparable to those previously observed by ourselves in heterozygous beta-thalassemia despite of the different Hb concentration in these thalassemic syndromes. This points to the existence of signals which regulate Ep synthesis independently of Hb levels.

[Vasoactive intestinal polypeptide in digestive processes in the Verner Morrison syndrome]. / Il vasoactive intestinal polypeptide in alcuni processi digestivi e nella sindrome di Verner Morrison.

Some physiological digestive processes thought to be under the control of VIP-ergic neurones are presented. The etiological role of the Vasoactive Intestinal Polypeptide in the Verner Morrison syndrome is discussed.

[The vasoactive intestinal polypeptide (VIP). Its role in the physiology of the digestive system]. / Il vasoactive intestinal polypeptide (VIP). Suo ruolo nella fisiologia dell'apparato digerente.

The literature on the possible implications of the Vasoactive Intestinal Polypeptide (VIP) in the digestive processes is widely and critically reviewed. Special attention is directed to the likely function of the polypeptide as a neurotransmitter in the gastroenteropancreatic system.

[Physiopathological and therapeutic implications of somatostatin in internal medicine. Recent aquisitions in some disease conditions]. / Implicazioni fisiopatologiche e terapeutiche della somatostatina in medicina interna. Recenti acquisizioni in alcune condizioni morbose.

In previous paper, the role of somatostatin in diabetes was examined. Here, the inhibitive action of somatostatin on growth hormone and its physiopathological and therapeutic implications in acromegaly and diabetes mellitus are reanalysed. The effect of the polypeptide on the C.N.S. is looked at from the viewpoint of its role as neurotransmitter at encephalic level and of its therapeutic use.