POR polymorphisms are associated with 21 hydroxylase deficiency.

PURPOSE: Genotype-phenotype correlation in congenital 21 hydroxylase deficiency is strong but by no means absolute. Indeed, clinical and hormonal features may vary among patients carrying similar CYP21A2 mutations, suggesting that modifier genes may contribute to the phenotype. Aim of the present study was to evaluate whether polymorphisms in the p450  oxidoreductase (POR) gene may affect clinical features in patients with 21 hydroxylase deficiency METHODS: Sequencing of the POR gene was performed in 96 patients with 21 hydroxylase deficiency (49 classic, 47 non-classic) and 43 control subjects. RESULTS: Prevalence of POR polymorphisms in patients with 21 hydroxylase was comparable to controls and known databases. The rs2228104 polymorphism was more frequently associated with non-classic vs classic 21 hydroxylase deficiency (allelic risk 7.09; 95% C.I. 1.4-29.5, p < 0.05). Classic 21 hydroxylase-deficient carriers of the minor allele in the rs2286822/rs2286823 haplotype presented more frequently the salt-wasting form (allelic risk 1.375; 95% C.I. 1.138-1.137), more severe Prader stage at birth (allelic risk 3.85; 95% C.I. 3.78-3.92), higher ACTH levels, and younger age at diagnosis. CONCLUSIONS: Polymorphisms in the POR gene are associated with clinical features of 21 hydroxylase deficiency both as regards predisposition to classic vs non-classic forms and severity of classic adrenal hyperplasia.

Measurement of height velocity is an useful marker for monitoring pituitary function in patients who had traumatic brain injury.

To assess the incidence of abnormal neuroendocrine function post-traumatic brain injuriy (TBI) in a large group of paediatric patients and its correlations with clinical parameters (Glasgow coma scale-GCS, Glasgow outcome scale-GOS, TC marshall scale, height velocity). We evaluated 70 patients [58 M, 12 F; age at the time of TBI (mean ± SEM) 8.12 ± 4.23 years] previously hospitalized for TBI at the "Regina Margherita" Hospital, in Turin and "Maggiore della Carità Hospital" in Novara, Italy, between 1998 and 2008. All patients included underwent: auxological, clinical, hormonal and biochemical assessments at recall (after at least 1 year from TBI to T0); auxological visit after 6 months (T6) and hormonal assessments at 12 months (T12) in patients with height velocity (HV) below the 25th centile. At T0, 4 cases of hypothalamus-pituitary dysfunction had been diagnosed; At T6 20/70 patients had an HV <25th centile, but no one had HV < the 3rd centile limit. At T12, among the 20 patients with HV <25th centile, in 13 patients the HV was below the 25th centile and GHRH + Arginine test has been performed. Four subjects demonstrated an impaired GH peak and were classified as GH deficiency (GHD). Of these 4 subjects, 3 subjects showed isolated GHD, while one patient showed multiple hypopituitarism presenting also secondary hypocortisolism and hypothyroidism. The GCS at admission and GOS do not correlate with the onset of hypopituitarism. A simple measurement of the height velocity at least 1 year after the TBI, is enough to recognize patients with a pituitary impairment related to GH deficiency. We suggest to follow-up paediatric population who had TBI with auxological evaluations every 6 months, limiting hormonal evaluation in patients with a reduction of height velocity below the 25th centile limit.

Phalangeal quantitative ultrasound in 1,719 children and adolescents with bone disorders.

SUMMARY: We measured bone properties by phalangeal quantitative ultrasound in 1,719 pediatric patients with bone disorders, classifying them according to fracture status. Quantitative ultrasound discriminated fractured and nonfractured pediatric patients and enabled us to stratify fractured patients into classes according to the severity of the causative trauma (spontaneous, minimal trauma, appropriate trauma fractures). INTRODUCTION: The correlation between quantitative bone measurements and fractures is poorly established in pediatric patients with bone disorders. We correlated phalangeal quantitative ultrasound (QUS) and fracture history in children and adolescents with bone disorders and evaluated the ability of QUS to recognize fractured patients. METHODS: Amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were measured in 1,719 pediatric patients with bone disorders and related to fracture history. The patients were classified as (1) spontaneously (77), (2) minimal trauma (101), or (3) appropriate trauma fractured (206), and (4) nonfractured (1,335). The likelihood of fracture according to QUS was calculated as odds ratio per SD decrease (OR/SD), and the effectiveness in discriminating fractured patients was evaluated by receiver operating characteristic (ROC) analysis. The influence of age, sex, puberty, height, and BMI was explored by respective adjustments and multiple logistic regression. RESULTS: Fractured patients showed significantly reduced AD-SoS and BTT standard deviation score (-0.32 ± 1.54 and -0.78 ± 1.49) compared to nonfractured subjects (0.43 ± 1.63 and -0.11 ± 1.34). QUS measurements paralleled the causative trauma severity, ranging from the lowest values in spontaneously fractured patients to normal values in appropriate trauma fractured subjects. The OR/SD were increasingly higher in appropriate trauma fractured, minimal trauma fractured, and spontaneously fractured patients. At ROC analysis, both parameters proved to have significant discrimination power in recognizing spontaneously and minimal trauma-fractured patients. CONCLUSIONS: QUS identifies fractured pediatric patients with bone disorders, reflecting the severity of the causative trauma with a high discrimination power for fragility fractures.

Genotype, phenotype and hormonal levels correlation in non-classical congenital adrenal hyperplasia.

Non-classical congenital adrenal hyperplasia (NCAH) is a morbid condition sustained by the reduced function of one of the enzymes involved in the adrenal steroid biosynthesis pathway, mainly the 21-hydroxylase. Different degrees of enzyme activity impairment determine different clinical pictures, with childhood or post-pubertal onset. The aim of this study was to evaluate the relationship between genotype, phenotype, and adrenal hormonal levels in a group of 66 patients affected by NCAH attending outpatient pediatric or endocrinological Clinics. Our findings show that age at pubarche/menarche was significantly younger, height SD score) and Δ bone age-chronological age were significantly higher in patients with a more severe enzyme activity impairment, while cutaneous androgenization and menstrual irregularities in post-pubertal girls were not related to the grading of genotype.

Correlation between genotype and hormonal levels in heterozygous mutation carriers and non-carriers of 21-hydroxylase deficiency.

Congenital adrenal hyperplasia, both in its classic (CCAH) and non-classic form (NCAH), is a morbid condition sustained by the absent or reduced function of one of the enzymes involved in cortisol biosynthesis - mainly 21 hydroxylase - associated with different levels of clinical androgenization. In a wide group of relatives of patients affected by CCAH and NCAH (no.=222) and healthy volunteers (no.=30), a clinical, hormonal and genetic evaluation was performed in order to differentiate between the condition of heterozygous mutation carrier and non-carrier of any among 21-hydroxylase gene (CYP21) mutations. This study shows that clinical presentation and basal 17α-hydroxyprogesterone (17α-OHP) are not able to differentiate between heterozygous carriers and non-carriers, whereas 17α-OHP value after ACTH bolus is significantly different between heterozygous carriers and non-carriers: p<0.001 with a cut-off value of 3 ng/ml (90% sensitivity and 74,3% specificity). Moreover, our data indicate that 17α-OHP response to ACTH may be a useful tool to select subjects for genetic analysis.

Hypothalamo-hypophysial dysfunction after traumatic brain injury in children and adolescents: a preliminary retrospective and prospective study.

With two study protocols, one retrospective and the other prospective, we evaluated hypothalamo-hypophysial dysfunction (HHD) in paediatric patients treated for traumatic brain injury (TBI) in the neurosurgical or intensive care department at our hospital. The retrospective group comprised 22 patients who had experienced TBI 0.7-7.25 years before the study. The prospective group included 30 patients assessed at TBI (T0), 26 of 30 after 6 months (T6), and 20 of 26 after 12 months (T12). Auxological and hormonal basal parameters of hypothalamo-hypophysial function were evaluated at recall in the retrospective group, and at T0, T6 and T12 in the prospective group. Basal data and standard dynamic tests in selected patients revealed one with precocious puberty, one with total anterior hypopituitarism, one with central hypogonadism, and one with growth hormone (GH) deficiency in the retrospective group; three patients with cerebral salt-wasting syndrome, one with diabetes insipidus and seven with low T3 syndrome at T0 (all transient), one with hypocorticism at T6 confirmed at T12, and one with GH deficiency at T12 in the prospective group. The results of our study show that post-TBI HHD in our paediatric cohort is not uncommon. Of the 48 patients who underwent a complete evaluation (22 retrospective study patients and 26 prospective study patients evaluated at T6) five (10.4%) developed HHD 6 months or more after TBI. HHD was newly diagnosed in one previously normal patient from the prospective group at 12 months after TBI. GH deficiency was the most frequent disorder in our paediatric cohort.

Characterization of early presentation idiopathic ovarian failure in girls and adolescents.

This study focused retrospectively on a selected cohort of 20 adolescents with early onset premature ovarian failure (POF) and no apparent underlying cause, in order to characterize the idiopathic ovarian failure at pediatric age. This characterization was based on medical history, pedigree analysis, phenotypical and audiological evaluation, final and target heights, pelvic ultrasonography, endocrine assessment, routine hematochemical analyses and complete autoimmune screening. We found that: a) idiopathic POF presented either before or after puberty onset and also with secondary amenorrhea; b) final height prognosis was impaired only in patients with prepubertal presentation of POF; c) ovarian pattern at ultrasonography and endocrine picture were similar those previously reported in patients with adult onset POF; d) clinical history and pedigree analysis, phenotypical and audiological examination and complete autoimmune screening failed to highlight the existence of any possible cause for POF in 15/20 patients; e) no alterations of total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol serum levels were detected in any patient. On the basis of these results we concluded that: a) final height of the adolescents with POF may be impaired only in patients in whom POF presents as a pubertal delay; b) other parameters do not generally differ from those described by previous reports on young adults with POF, except for serum lipid levels which were normal in the present cohort.

Final height in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: the Italian experience.

OBJECTIVE: To investigate the influence of target height (TH), gender, phenotype, glucocorticoid formulation and age at onset of treatment on final height (FH) in patients with 21-hydroxylase deficiency (21OHD). PATIENTS: Clinical data of 93 patients--46 simple virilizing (SV), 35 salt-wasting (SW) and 12 late onset (LO)--were collected in six pediatric endocrinology units in Italy. RESULTS: FH and TH were always below the mean height of the general population (mean FH, SDS: SW patients -1.3 +/- 1.2, SV patients -1.8 +/- 0.9, LO patients -1.7 +/- 1.1; mean TH, SDS: SW patients -0.6 +/- 0.8, SV patients -0.7 +/- 0.9, LO patients -1.4 +/- 1.3). FH was significantly below TH in patients with classic form (SW and SV, p <0.001), but not in LO patients. In classic form, TH seems to be related to FH, followed by age at onset of therapy and by steroid formulation, these variables explaining 30% of FH variance. CONCLUSIONS: In the classic form, substitutive therapy started before 21 months of age improved the long-term outcome. Lower TH in LO patients could be due to undiagnosed non-classic 21OHD in some of their parents. FH in LO patients seems not to benefit from corticosteroid therapy, even if late diagnosis may partly account for this result.

Accuracy of fine needle aspiration biopsy of thyroid nodules in detecting malignancy in childhood: comparison with conventional clinical, laboratory, and imaging approaches.

In childhood the traditional diagnostic approach to thyroid nodules consists of clinical, laboratory, and imaging evaluations. A safe and accurate procedure is needed to promptly identify patients who require surgery. In regard to the usefulness of fine needle aspiration biopsy, the data in the literature concerning children and adolescents are scanty. The aim of this study was to evaluate and compare the diagnostic accuracies of clinical, laboratory, and imaging data collected retrospectively in a group of pediatric patients with thyroid nodules submitted to fine needle aspiration biopsy. Forty-two patients who underwent surgery for thyroid nodules, recruited in 9 Italian pediatric endocrine units, were retrospectively studied. According to histological diagnosis, they were divided into 2 groups, 22 patients with benign lesions and 20 patients with malignant lesions. From clinical records we obtained data about 1) symptoms of neck compression; 2) cervical adenopathy; 3) thyroid function, calcitonin level, and antithyroid antibody titers; 4) ultrasonography; 5) (99m)Tc scintiscanning; and 6) cytology obtained with fine needle aspiration biopsy. Patients and nodule characteristics were analyzed statistically for associations with the presence of thyroid cancer. Among clinical findings, only adenopathy was significantly higher in the group with cancer (8 of 22 benign lesions vs. 16 of 20 malignant lesions; P = 0.006). Thyroid function and antibody titers were similar in the 2 groups, whereas the serum calcitonin level was elevated only in 1 patient with malignant lesions. Among ultrasonography findings, no significant statistical difference was found between the 2 groups with regard to number, dimensions, growth progression, or hypoechogenic pattern of the nodules. Regarding scintigraphic findings, no significant difference was found between the 2 groups. However, a positive correlation (r = 0.90; P < 0.0001) was found between fine needle aspiration biopsy cytological findings and histological diagnoses. The sensitivity, specificity, and accuracy of fine needle aspiration biopsy were 95%, 86.3%, and 90.4%, respectively. A multiple regression analysis showed that only fine needle aspiration biopsy (beta coefficient = 0.963; P < 0.0001) significantly contributed to detecting malignancy (multiple r = 0.973; P < 0.0001). This study provides strong evidence that fine needle aspiration biopsy is a safe technique even in childhood and adolescence, offering the best sensitivity, specificity, and accuracy in detecting malignancy compared with conventional approaches.

Thyroid dysfunction as a late effect in childhood medulloblastoma: a comparison of hyperfractionated versus conventionally fractionated craniospinal radiotherapy.

PURPOSE: Primary hypothyroidism is a common sequela of craniospinal radiotherapy in the treatment of childhood medulloblastoma. Due to the strong radiobiologic rationale, hyperfractionation can reduce the delayed effects of radiation injury. METHODS AND MATERIALS: The authors compared the incidence of thyroid dysfunction after conventionally fractionated radiotherapy (Group A, n = 20 patients) vs. hyperfractionated radiotherapy (Group B, n = 12 patients) in a group of pediatric patients with posterior fossa primitive neuroectodermal tumor (PNET). RESULTS: The mean age at the time of tumor diagnosis was 7.4 years in Group A and 8.4 years in Group B. Thyroid function was evaluated yearly, with ultrasonographic examination every 2 years. The patients were followed after diagnosis for a mean of 10.8 years for Group A and 6.0 years for Group B. Approximately 80% of the Group A (16/20) and 33.3% of the Group B (4/12) patients developed primary hypothyroidism within a similar period after irradiation (4.2 vs. 3.5 years, respectively). Analysis by cumulative incidence function demonstrated a significant difference in the risk of developing thyroid dysfunction between these two groups of patients (p < 0.05). Ultrasonography showed reduced thyroid volume in 7 Group A patients and structural changes in 21 patients (17 Group A, 4 Group B cases); a thyroid benign nodule was detected in 2 Group A patients. CONCLUSIONS: The current study findings suggest that the use of hyperfractionated craniospinal radiotherapy in the treatment of childhood medulloblastoma is associated with a lower risk of these patients' developing late thyroid dysfunction.

Thyroid diseases in patients treated during pre-puberty for medulloblastoma with different radiotherapic protocols.

We evaluated thyroid disease in 32 patients treated, during pre-puberty, for medulloblastoma, followed for at least 4 years and without relapse during observation. After surgery the patients underwent chemotherapy (CT) and radiotherapy (RT). The protocols were as follows: 20 patients (group A) SNC 76 and SNC 85 protocols which included conventional fractionated RT (36-40 Gy to the craniospinal axis and a 14-18 Gy boost to the posterior fossa, administered as 1.5-1.8 Gy per fraction per day) and a junction between the cranial and the spinal fields at C2-C3 level; 12 patients (group B) SNC 91 protocol which included hyperfractionated RT (36 Gy to the craniospinal axis and a 30 Gy boost to the posterior fossa; this was administred as 1 Gy per fraction twice per day) and a junction at levels C5-C6 or C6-C7 level. The mean age at diagnosis was 7.4+/-3.2 years for group A and 8.4+/-2.6 years for group B. Thyroid function was evaluated yearly and ultrasonographic characteristics every 2 years. The patients were followed for a mean of 10.8+/-3.8 for group A and 6+/-1.4 years for group B. Primary hypothyroidism was diagnosed in 16 group A patients and 4 group B patients, and central hypothyroidism was diagnosed in 2 group A patients (difference in risk of developing hypothyroidism evaluated with a Wilcoxon-test: p=0.048). Ultrasonography showed reduced thyroid volume in 7 group A cases, and structural changes in 21 patients (17 group A, 4 group B); 9 L-thyroxine-treated patients were confirmed hypothyroid after having stopped therapy. A thyroid nodule was detected in two cases (one from each group). In conclusion, our data indicate that thyroid injury may be diminished by the use of hyperfractionation and low-junction radiotherapy in the treatment of medulloblastoma.

17alpha-hydroxylase/17,20-lyase deficiency as a model to study enzymatic activity regulation: role of phosphorylation.

Cytochrome P450 17alpha-hydroxylase (CYP17) is a single gene-encoded protein with two activities: 17alpha-hydroxylase and 17,20-lyase. The two catalytic activities are differentially regulated in health and disease. We took advantage of naturally occurring human mutations to understand the molecular bases of this differential regulation. We identified eight novel mutations in the CYP17 gene, different in nature and spread throughout the gene. As posttranslational modifications appear to be important for activity control, we investigated the phosphorylation state of wild-type and mutant CYP17 proteins. Although phospholabeled protein was seen when the wild-type and most mutant proteins were expressed, no phosphorylation was detected for the F417C mutant. F417C is the only 17,20-lyase deficiency case confirmed at the molecular level and represents the first phosphorylation CYP17-deficient mutant. In search of the physiological agents involved in this process, the effect of cAMP was tested on activity and phosphorylation state of our mutant CYP17 proteins. cAMP stimulates activity and phosphorylation in all cases, except in the F417C and R35L mutants. The lack of response to the physiological second messenger might explain the different phenotypes. The F417C mutant protein, which is already shown to be associated with the lack of electron transfer, provides for the first time a link between the electron transfer system and the phosphorylation state of the CYP17 enzyme in the control of 17,20-lyase activity.

T426I a new mutation in the thyroid hormone receptor beta gene in a sporadic patient with resistance to thyroid hormone and dysmorphism. Mutations in brief no. 192. Online.

Resistance to thyroid hormone (RTH) is a rare inherited autosomal syndrome caused by mutations in the thyroid hormone receptor beta (TRb) gene. Although RTH is generally a familiar disease, 15% of sporadic cases have been also reported. So far, about 80 different mutations of TRb gene have been identified in patients affected by RTH. All these mutations localize to the binding domain and most of them cluster within two "hot spots" (codons 310-349 and codons 429-460). Here we describe in a patient with RTH, a new mutation in codon 426 (T426I) of the TRb gene leading to a threonine to isoleucine substitution. This is a "de nova" mutation which localizes in the so-called "cold" region, outside the two known "hot spots". The patient had the hallmark of RTH: elevated FT3 and FT4, normal TSH, and clinical features of both hypo and hyperthyroidism. Moreover, several dysmorphisms were present including triangular face appearance, synophris, low set ears, micrognathia with malocclusion, large upper incisors and apparent lack of lower cuspids which have not previously described in RTH patients.

Growth hormone treatment in irradiated children with brain tumors.

We assessed the efficacy of GH treatment in 25 GH deficient patients irradiated for brain tumors (eight with glioma cranio-irradiated, eleven with medulloblastoma and six with ependymoma craniospinal-irradiated). We administered GH at doses of 0.6-0.9 IU/kg/week for one to three years at least two years after diagnosis of the tumor. We assessed the efficacy of the treatment each year by comparing the values of height velocity over bone age and change in the ratios progression of chronological age/progression of bone age and progression of statural age/progression of bone age. The treatment promoted satisfactory growth; better results were obtained in patients with glioma, who received cranial irradiation only, than in those with medulloblastoma or ependymoma, who received spinal irradiation as well. Moreover, the growth prognosis improved, especially in the cranio-irradiated patients. In our series of patients four presented tumor recurrence; these results did not differ significantly from those in irradiated patients with cerebral tumors who were not treated with GH.

HLA haplotypes and hormonal studies in 25 Italian families of patients with classical and non-classical 21-OH deficiency.

To investigate the genetic polymorphisms of the HLA region and the molecular defect of the P450c21B gene in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, we studied 89 individuals from 25 families of CAH patients (14 classical forms, 11 non-classical forms). The following immunogenetic and hormonal investigations were performed: HLA-A and B typing, restriction fragment length polymorphism (RFLP) analysis of 21-hydroxylase A and B genes, and serum 17-OH-progesterone values determined basally and 60 min after ACTH stimulation. In the patients affected by the classical form, RFLP analysis revealed 5 deletions and 1 gene conversion in 6 haplotypes and no molecular defect in the others, who probably carry point mutations. In the patients with non-classical form we found P450c21A duplication in 11/18 haplotypes; 9 of the 11 patients shared the HLA-B14 allele. Utilizing both hormonal and genetic data we identified two cryptic forms; hormonal data alone failed to differentiate heterozygous from normal individuals.

Auxological and biochemical parameters in assessing treatment of infants and toddlers with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

We studied height velocity (HV), bone age progression (delta BA/delta CA), urinary pregnanetriol (PT) and plasma 17-hydroxyprogesterone (17-OH-P) during the first years of life in 12 patients with 21-hydroxylase deficiency, treated by cortisone acetate. In the well-controlled phases normal growth rate (SDS between -1 and +1), satisfactory bone age progression (delta BA/delta CA < or = 1) and no clinical sign of poor treatment were found; in the undertreatment phases enhanced growth rate, rapid bone age progression and, in some instances, signs of virilization were found; in the overtreatment phases, reduced growth rate was the only sign of poor treatment. Hormonal values were only weakly correlated to therapeutic control. Therefore, growth rate evaluation can represent the best method of monitoring treatment in very young patients with 21-hydroxylase deficiency.

[Diagnosis of ambiguous genitalia]. / Diagnostica nelle ambiguità dei genitali.

Diagnosis in patients with ambiguous genitalia is based on various investigations. Simple genital examination is not sufficient to attribute sex. Scarce androgenization in a male patient or marked androgenization in a female may both lead to the same stages of genital ambiguity according to Prader. It is important to get information about genital ambiguity in the family, drug consumption during gestation and signs of virilization in pregnant mothers. External genital findings must be integrated by visualization of urogenital sinus by X-rays, ultrasounds and endoscopy. Furthermore, hormonal evaluations on plasma and 24 hours urines allow diagnosis of some disorders of adrenal and gonadal steroidogenesis. To define genetic sex, chromosomal examination is required to integrate X chromatine investigation and fluorescent staining of Y chromosome. Evaluation of psychosexuality in patients who have already got gender identity is mandatory.

L-asparaginase-induced coagulopathy in children with acute lymphoblastic leukaemia.

Haemostatic changes induced with vincristine (VCR), prednisone (PDN) and L-asparaginase (L-ase) in 53 children with ALL were prospectively evaluated. Relative to pretreatment values, mean FG concentration diminished significantly in the first week with a minimal level in the third week and PT was prolonged during the first weeks of induction. APTT decreased significantly in the last week and after cessation of L-ase therapy. Mean concentration of factor VIII remained elevated during the entire period of L-ase therapy. Three children (5.6%) developed a cerebral thrombo/haemorrhagic complication. These data demonstrate that the tendency for thrombosis is the predominant clinical manifestation of L-ase-induced coagulopathy, when the drug is associated with VCR and PDN.

[The glucose-6-phosphate dehydrogenase/6-phosphogluconate dehydrogenase ratio in the identification of glucose-6-phosphate dehydrogenase heterozygosity]. / Il rapporto G-6PD/6-PGD nella identificazione dell' eterozigosi per la G-6PD.

Deficiency in human G-6PD is a widespread X-linked disorder, which is mainly characterized by susceptibility to hemolytic anaemia after the ingestion of certain drugs or toxic substances (e.g. pyrimidine derivates contained in fava beans). G-6PD deficiency in hemizygous males in easily detectable since enzymatic activity is almost absent. In heterozygous subjects the determination of enzymatic activity on red cell lysate cannot detect a partial G-6PD deficiency. Cytochemical methods as methemoglobin reduction test or tetrazolium reduction test are more sensitive than spectrophotometric quantitative test, but are not suitable for screening purposes. We measured both G-6PD activity and 6-PGD activity in G-6PD heterozygous females and we evaluated the G-6PD/6PGD ratio. We tested this ratio also in thalassemic traits and in G-6PD heterozygotes with thalassemic trait in order to detect the interference of thalassemic pathology with the phenotypic expression of the gene for G-6PD. We found that the mean G-6PD values were statistically reduced in G-6PD heterozygous females; on the contrary the measurement of true G-6PD activity alone is not a good tool for discriminating heterozygous subjects with and without thalassemic trait. Actually 100% and 79% of values observed were in the normal range +/- 2 DS respectively. The mean G-6PD/6-PGD ratio in heterozygotes for G-6PD deficiency with and without thalassemic trait was lower than normal and the individual values of G-6PD/6-PGD ratio were in the normal range +/- 2 DS only in a few subjects (8.3% and 10.7% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

[Therapy of idiopathic thrombocytopenic purpura]. / Terapia delle porpore trombocitopeniche idiopatiche.

Various treatment strategies for acute and chronic idiopathic thrombocytopenic purpura (ITP) in childhood are reviewed. In acute ITP steroids induce a prompt improvement of symptoms and a rapid increase in platelet count; the use of high dose intravenous immunoglobulin is a valid alternative treatment to steroids. In chronic ITP splenectomy is still the most successful treatment, as it induces remission in 60-80% of patients. The risk for severe infections after splenectomy is still considerable in children; therefore other treatment schedules are suggested (i.v. immunoglobulin, courses of steroids, high dose methylprednisolone). In this paper we report 100 pediatric cases with acute ITP and 36 with chronic ITP.