The Italian National Survey for Prader-Willi syndrome: an epidemiologic study.

Twenty-five medical centers and the Prader-Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.4-46.7). Two hundred thirty-eight patients had del15, 104 had UPD15, 4 demonstrated a translocation affecting chromosome 15 and 79 showed a positive methylation test. There were fewer subjects found over the age of 35, probably due to the low rate of identification of older PWS patients as well as the high mortality rate. There were a greater number of male children and adolescents with PWS whilst, amongst adults, there were more females. As expected, the majority of subjects with PWS were obese, especially in adult life. Nevertheless, it is noteworthy that 26% of patients aged between 6 and 17 were normal weight. A total of 212 subjects had received GH treatment, of which 141 were still receiving therapy, while the remaining 71 had stopped. In children and adolescents (233 cases), 89 subjects had never undergone GH therapy. Eighteen PWS patients had died in the past 20 years. Obesity-related cardiovascular and respiratory diseases were the cause of death, both during childhood and after 18 years of age. Three children died suddenly whilst undergoing GH therapy. Respiratory infection and cardiac illness were the causes of death in two cases. There was no definitive cause of death found in the third case. Overall, there was no increase in number of deaths during GH treatment, suggesting that GH administration in patients with PWS, as a group, does not increase the risk of death.

Brain white matter impairment in congenital adrenal hyperplasia.

BACKGROUND: Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis. Past reports suggested that brain white matter could be involved in CAH. OBJECTIVE: To detect the presence, and possible changes over time, of brain white matter abnormalities in patients with CAH. DESIGN: Neurological examination and brain magnetic resonance imaging (MRI) that were repeated in 12 patients after a mean interval of 11 years. SETTING: Pavia, northern Italy. Patients Twenty-two patients with CAH. MAIN OUTCOME MEASURES: Evaluation of clinical neurological findings and brain MRI T2-weighted images. RESULTS: Ten (45%) of 22 patients with CAH had white matter abnormalities (diffuse in 4 cases, focal in 3 cases, and both diffuse and focal in 3 cases) on MRI. The MRI findings never changed over repeated assessments. CONCLUSIONS: Subclinical brain white matter involvement is frequent in CAH. This might be due to hormonal imbalance during brain development or corticosteroid treatments. Our study findings indicate that a relationship with demyelinating diseases can also be suggested. Diagnosis of CAH should be suspected in young subjects with brain MRI white matter abnormalities that are not otherwise explicable.

Congenital adrenal hyperplasia and multiple sclerosis: is there an increased risk of multiple sclerosis in individuals with congenital adrenal hyperplasia?

BACKGROUND: Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis, generally caused by a total or partial deficiency in 21-hydroxylase, due to a deletion of or mutations in the CYP21 gene (the gene that codes for 21-hydroxylase). Impaired cortisol biosynthesis results in corticotropin hypersecretion, which leads to overproduction of intermediate metabolites and androgens. OBJECTIVE: To describe for the first time, to our knowledge, a patient with CAH and multiple sclerosis (MS). DESIGN: Case report. PATIENT: A 22-year-old woman, diagnosed at birth as having a salt-losing 21-hydroxylase deficiency, had sudden visual loss in the right eye and pyramidal, sensory, and cerebellar signs. Repeated brain magnetic resonance images showed focal white matter lesions in periventricular areas, the corpus callosum, the cerebellum, and the brainstem. A cerebrospinal fluid examination revealed several oligoclonal bands. Thereafter, she had 2 relapses, characterized by ataxia and diplopia, and recovered after corticosteroid treatment. RESULTS: The reported case fulfills the diagnostic criteria for CAH and MS. CONCLUSIONS: Some clues suggest that the association between CAH and MS could be nonincidental: a possible MS susceptibility locus is on chromosome 6p21, on which the CYP21 gene is located; the CYP21 gene and the CYP21P pseudogene alternate in tandem with the C4 genes (the genes that code for the homonym complement protein) (C4AQ0 is particularly frequent in patients with relapsing-remitting MS); and, in previous studies, brain magnetic resonance imaging showed T2-hyperintense focal areas in the white matter of CAH patients. Our observation should alert neurologists to the presence of signs and symptoms suggestive of late-onset CAH in MS patients and, in turn, endocrinologists to the appearance of neurological signs and symptoms in CAH patients.

Evaluation of xenobiotics in human milk and ingestion by the newborn--an epidemiological survey in Lombardy (Northern Italy).

BACKGROUND: Many human milk benefits have been well documented; nevertheless the newborn potential risk to the xenobiotic exposition may be relevant and it requires a biological monitoring in general prevention. Concerning this problem, attention should be paid to mycotoxins and heavy metals. AIM OF THE STUDY: Assessing the presence of the xenobiotics aflatoxins, ochratoxin A, lead and cadmium in human milk, defining their level of contamination and evaluate the potential risk for the newborn derived from this xenobiotic ingestion. METHODS: A study has been carried out on lactating women randomly selected in seven hospitals in Lombardy (Northern Italy). Two hundred and forty-seven puerparae were recruited; 231 women participated in the study. Women's milk samples on the third or fourth day after delivery were tested to determine aflatoxins and ochratoxin A levels. Lead and cadmium were determined in 143 women because supplemental milk could be taken only from these women. RESULTS: Aflatoxin B1 (11.4 ng/l) and aflatoxin M1 (194 ng/l) were found only in one sample,while ochratoxin A was detected in 198 samples (85.7 %) at an average value of 6.01 +/- 8.31 ng/l. A total of 75.7% of samples were positive for lead; the cadmium situation was better with 87.4% of the sample with values below detection limits (2 microg/l). A high percentage of babies (71 %) are exposed to mycotoxin levels on day 6 greater than the TDI value of 0.2 ng/kg b.w. Lead and cadmium presence in human milk presented risk respectively for 8% and 0.7% of newborns on the fourth day; 9.5% and 1.4% on the sixth day. CONCLUSIONS: The study points out that mycotoxins and lead are present in maternal milk, and the data confirm the need to continue biological monitoring in general prevention.