Monia Gennari

EARLY PREDNISONE TREATMENT IN DUCHENNE MUSCULAR DYSTROPHY

The purpose of this long‐term, open parallel‐group, double‐consent study of alternate‐day, low‐dose prednisone in 2–4‐year‐old patients with Duchenne muscular dystrophy (DMD) was to determine whether prednisone produces a beneficial effect when given earlier than usual. Muscle function was evaluated by timed tests, and muscle strength with a hand‐held myometer. After 55 months of treatment, the five patients (mean age 8.3 years) in the prednisone group were still able to get up from the floor, whereas two of the three in the control group had lost this ability. Side effects included a decline in growth rate in the prednisone‐treated patients and excessive weight gain in one control and three treated patients. Because steroids are effective in prolonging function, but not in recovering lost function, we propose that treatment be started with low‐dose prednisone in DMD patients as soon as the diagnosis is definite. Muscle Nerve 27: 222–227, 2003

Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up.

Corticosteroid treatment is the standard of care in Duchenne muscular dystrophy (DMD), but the optimal age to initiate treatment and dosage pattern remain a matter of discussion.

Characterization of deletions at 9p affecting the candidate regions for sex reversal and deletion 9p syndrome by MLPA

The distal region on the short arm of chromosome 9 is of special interest for scientists interested in sex development as well as in the clinical phenotype of patients with the 9p deletion syndrome, characterized by mental retardation, trigonocephaly and other dysmorphic features. Specific genes responsible for different aspects of the phenotype have not been identified. Distal 9p deletions have also been reported in patients with 46,XY sex reversal, with or without 9p deletion syndrome. Within this region the strongest candidates for the gonadal dysgenesis phenotype are the DMRT genes; however, the genetic mechanism is not clear yet. Multiple ligation-dependent probe amplification represents a useful technique to evaluate submicroscopic interstitial or distal deletions that would help the definition of the minimal sex reversal region on 9p and could lead to the identification of gene(s) responsible of the 46,XY gonadal disorders of sex development (DSD). We designed a synthetic probe set that targets genes within the 9p23-9p24.3 region and analyzed a group of XY patients with impaired gonadal development. We characterized a deletion distal to the DMRT genes in a patient with isolated 46,XY gonadal DSD and narrowed down the breakpoint in a patient with a 46,XY del(9)(p23) karyotype with gonadal DSD and mild symptoms of 9p deletion syndrome. The results are compared with other patients described in the literature, and new aspects of sex reversal and the 9p deletion syndrome candidate regions are discussed.

SRD5A2 gene analysis in an Italian population of under-masculinized 46,XY subjects

Objective  The differential diagnosis of male under‐masculinization, including a wide spectrum of phenotypes and a heterogeneous genetic basis, is crucial for the correct management of the patients. To characterize an Italian population of under‐masculinized males, we performed the molecular analysis of the SRD5A2 gene (2p23), encoding the 5α‐reductase‐2 enzyme that converts testosterone (T) to dihydrotestosterone (DHT), and is required for full masculinization of the male foetus.

Active and total ghrelin concentrations in the newborn

BACKGROUND Ghrelin is a peptide with a potent capacity to release GH and other metabolic activities. An acyl modification is indispensable for biological activity. Acylated and desacylated forms of ghrelin are both present in the blood. No data exist about the ratio between active ghrelin and total ghrelin in the first period of life. OBJECTIVE To investigate whether ghrelin may be involved in physiological roles during fetal life. INFANTS AND METHODS Ghrelin, growth hormone (GH), and leptin concentrations were measured in cord plasma in 98 newborns of healthy mothers. Acyl-ghrelin and the sum of acylated and desacylated forms of ghrelin (total ghrelin) were measured using specific radioimmunoassays. RESULTS Acylated ghrelin and total ghrelin did not correlate with birth weight, gestational age, body mass index, head circumference, birth length, leptin or GH in plasma cord blood. CONCLUSIONS The absence of clinically significant correlations between both active and total ghrelin and GH, leptin or anthropometric data does not enable us to ascribe a precise role to ghrelin in prenatal life.

A novel PRKAR1A mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations

Context  Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome (OMIM 160980). About 70% of cases are familiar; most have mutations of the PRKAR1A gene on chromosome 17q22–24. There is little phenotype–genotype correlation known to date.

Growing Up with Type 1 Narcolepsy: Its Anthropometric and Endocrine Features.

STUDY OBJECTIVES To evaluate the effect of type 1 narcolepsy (NT1) on anthropometric and endocrine features in childhood/adolescence, focusing on patterns and correlates of weight, pubertal development, and growth in treated and untreated patients. METHODS We collected anthropometric (height, weight, body mass index (BMI) z-scores), pubertal, metabolic, and endocrine data from 72 NT1 patients at diagnosis and all available premorbid anthropometric parameters of patients from their pediatric files (n = 30). New measurements at 1-y reassessment in patients undergoing different treatments were compared with baseline data. RESULTS We detected a high prevalence of overweight (29.2%), obesity (25%), metabolic syndrome (18.8%), and precocious puberty (16.1%), but no signs of linear growth alterations at diagnosis. According to anthropometric records, weight gain started soon after NT1 onset. At 1-y follow-up reassessment, sodium oxybate treatment was associated with a significant BMI z-score reduction (-1.29 ± 0.30, p < 0.0005) after adjusting for baseline age, sex, sleepiness, and BMI. CONCLUSIONS NT1 onset in children/adolescents is associated with rapid weight gain up to overweight/obesity and precocious puberty without affecting growth. In our study, sodium oxybate treatment resulted in a significant weight reduction in NT1 overweight/obese patients at 1-y follow-up.

Emotion Recognition and Expression in Young Obese Participants: Preliminary Study:

This study of the presence of alexithymic characteristics in obese adolescents and preadolescents tested the hypothesis of whether they showed impaired recognition and expression of emotion. The sample included 30 obese young participants and a control group of 30 participants of normal weight for their ages. Stimuli, 42 faces representing seven emotional expressions, were shown to participants who identified the emotion expressed in the face. The Level of Emotional Awareness Scale was adapted for children to evaluate their ability to describe their emotions. Young obese participants had significantly lower scores than control participants, but no differences were found in recognition of emotion. The lack of words to describe emotions might suggest a greater prevalence of alexithymic characteristics in the obese participants, but the hypothesis of a general deficit in the processing of emotional experiences was not supported.

Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) concentrations compared to stimulated growth hormone (GH) in the evaluation of children treated for malignancy.

OBJECTIVE The aim of this investigation was to evaluate the utility of IGF-I and IGFBP-3 determinations in screening for GH deficiency (GHD) in children previously submitted to treatment for childhood malignancy. PATIENTS AND METHODS We compared the GH responses to two pharmacological tests (arginine and levo-dopa) with the IGF-I and IGFBP-3 levels in 48 patients (29 boys) who had undergone bone marrow transplantation (BMT) (36 patients) or treatment for a solid cranial tumor (12 patients). RESULTS 22 patients (45.8%) showed GHD (i.e. GH peak < 8 ng/ml in both tests), and only three (13.6%) of the GHD patients had concomitant low IGF-I levels (i.e. -2 SD below the normal mean) and only one (4.5%) an abnormal IGFBP-3 value (i.e. -2 SD below the normal mean). Among the 26 children with normal GH secretion, 21 (80.8%) also showed normal IGF-I and IGFBP-3 levels, three (11.5%) had a concomitant low IGF-I value and two (7.7%) a concomitant low IGFBP-3 value. A significant correlation was found between GH secretion and age at diagnosis (r = 0.26, P < 0.05), and between IGF-I and IGFBP-3 (r = 0.52, P < 0.0001), but not between GH and IGF-I or IGFBP-3. Comparing the growth pattern of these patients from diagnosis to the first year after therapy or BMT, we found that while individual height changes did not correlate with the GH peak, a significant correlation was found between height SDS decrease and IGF-I (r = 0.31, P < 0.05) or IGFBP-3 SDS (r = 0.37, P < 0.01). CONCLUSION Our results indicate that the cut-off of -2 SD for IGF-I and IGFBP-3 was insensitive in screening for GHD. A normal value did not exclude a subnormal GH response to provocative tests and therefore although IGF-I and IGFBP-3 levels may be indicators of the growth pattern, they cannot be used alone as a tool for identifying GHD children after treatment for childhood malignancy.

Three novel AMH gene mutations in a patient with persistent mullerian duct syndrome and normal AMH serum dosage.

Background:Persistentmüllerian duct syndrome (PMDS) is characterized by the presence of uterus, fallopian tubes and the upper part of the vagina in 46,XY patients with perfectly virilized external genitalia. It is mostly caused by mutations of the AMH or AMH type 2 receptor (AMHR2) gene. The AMH serum level is very often low or undetectable in the AMH gene defect and normal in the AMHR2 gene defect. Aim: We investigate an Italian patient, genotypically and phenotypically male, observed at 1 month of age for a right inguinal hernia that at surgery showed the presence of both testes in the same hernial sac and uterus and fallopian tubes in the abdomen. Results: Genetic tests first showed the absence of the common 27-bp deletion in the AMHR2 gene, then the presence of three new sequence variations in the AMH geneleading to the following variants: the p.A405P carried by the paternal allele; the p.G326V plus the p.V508A carried by the maternal allele. Conclusions: The determination of serum AMH, performed after the genetic analysis, showed a normal level for age, suggesting that these mutations may affect the function and the bioactivity of the hormone and not the secretion rate.