Medical, psychological and social features in a large cohort of adults with Prader-Willi syndrome: experience from a dedicated centre in France.

BACKGROUND: Prader-Willi syndrome (PWS) is a developmental genetic disorder characterised by a variable expression of medical, cognitive and behavioural symptoms. In adulthood, the prevalence and severity of these symptoms determine the quality of life of the affected persons. Because of their rare disease condition, data on health and social problems in adults with PWS are scarce. In this research, we present medical, psychological and social features of a large cohort of adults admitted to a specialised PWS centre in France and analyse the differences according to genotype, gender and age. METHODS: Data from 154 patients (68 men/86 women), with a median age of 27 years (range 16-54), were collected during their stay in our centre. Clinical histories were completed using information from parents or main caregivers, and the same medical team performed the diagnosis of different clinical conditions. Statistical analyses were performed to determine the influence of factors such as genotype, age or gender. RESULTS: Paternal deletion genotype was the most frequent (65%) at all ages. Most patients had mild or moderate intellectual disability (87%). Only 30% had studied beyond primary school and 70% were in some special educational or working programme. Most of them lived in the family home (57%). The most prevalent somatic comorbidities were scoliosis (78%), respiratory problems (75%), dermatological lesions (50%), hyperlipidaemia (35%), hypothyroidism (26%), Type 2 diabetes mellitus (25%) and lymph oedema (22%). Some form of psychotropic treatment was prescribed in 58% of subjects, and sex hormones in 43%. Patients with deletion had a higher body mass index (44 vs. 38.9 kg/m(2)) and displayed higher frequency of sleep apnoeas. Non-deletion patients received insulin treatment (19% vs. 4%) and antipsychotic treatment (54.8% vs. 32.7%) more frequently. No difference was observed in the prevalence of Type 2 diabetes between the two genotype groups. Patients >27 years of age had a higher rate of comorbidities (Type 2 diabetes, hypertension, respiratory problems and lymph oedema). Gender differences were minor. CONCLUSIONS: Adult patients with PWS showed high prevalence of comorbid health problems that need to be monitored for early treatment. Some of them are influenced by genotype and age. Another salient problem concerns the lack of adapted structures for better social integration. Further data about the real life and health conditions of adults with PWS are necessary to further our knowledge of the natural history of the disease and to design appropriate care strategies.

[Turner's syndrome and procreation. Ovarian function and Turner's syndrome]. / Syndrome de Turner et procréation. Fonction ovarienne et syndrome de Turner.

Ovarian failure is a typical feature in Turner's syndrome. The majority of follicles disappears prematurely after a normal determination of the ovary. This results from an accelerated loss of oocytes from the ovaries after the 18th week of fetal life or over a few postnatal years, usually before the onset of puberty. The cause and mechanism of this loss are unknown. X chromosomal anomaly due to deletions or haploinsufficiency of genes can explain the various degrees of ovarian failure. Spontaneous puberty occurs in 20-30% of Turner syndrome patients and their fertility rates vary from 5 to 10%. This indicates the possible presence and maturation of follicles in their ovaries in adolescence. In ovarian failure, the hormone replacement therapy (HRT) is necessary to achieve the development of normal female sexual characteristics, the self image or social functioning and to prevent osteoporosis. Pregnancy is now possible with oocyte donation. A careful cardiovascular follow-up is necessary. Cryoconservation represents one way for preserving the future fertility, but the optimal age of ovarian biopsy has to be studied.

[Retroperitoneal laparoscopic adrenalectomy in a pregnant woman presenting MEN2a with a pheochromocytoma: case report and review of the literature]. / Surrénalectomie par coelioscopie rétropéritonéale au cours de la grossesse chez une patiente présentant un phéochromocytome dans le cadre d'une NEM2a: un nouveau cas et revue de la littérature.

The diagnosis of pheochromocytoma during pregnancy is uncommon and is at high risk for both mother and baby. We report the case of a 22-year-old woman with MEN2a (mutation C634Y in exon 11 of RET) who had undergone surgery for medullary carcinoma of the thyroid and hyperparathyroidism when she was 18. She was asymptomatic when she was seen at 22 weeks of gestation because of increased urinary metanephrine levels. A 24-h blood pressure monitoring was normal. Abdominal magnetic resonance imaging (MRI) revealed a right-sided, 34x31x28mm, well-limited, adrenal mass with high signal intensity on T2-weighted images; the contralateral adrenal was normal. At 26 weeks of gestation and after an adequate labetalol preparation, a retroperitoneal laparoscopic right-sided adrenalectomy was performed without maternal or foetal complications. Pathohistological examination confirmed the presence of a 3cm pheochromocytoma in the right adrenal gland, with no sign of malignancy. The levels of urinary methoxylated metabolites were normal two months after surgery. The pregnancy progressed normally and the patient delivered a healthy child without complications. In conclusion, firstly, all MEN2a women should be screened for a pheochromocytoma with a 24-h urinary metanephrine and normetanephrine evaluation before or early during pregnancy, even with normal blood pressure; secondly, pheochromocytoma diagnosed during pregnancy should be operated on during pregnancy because of the risks for both mother and baby; thirdly, after medical therapy, retroperitoneal laparoscopic adrenalectomy can be performed during the second trimester of pregnancy.

[Pemphigoid gestationis and Turner syndrome; an uncommon association]. / Pemphigoïde de la grossesse et syndrome de Turner ; une association inhabituelle.

The authors report an uncommon case of a pregnant woman with Turner syndrome (TS) whose pregnancy (with favorable outcome) was complicated by a pemphigoid gestationis in third trimester. This case points out that monitoring of these pregnancies is not limited to cardiac monitoring. Prevalence of auto-immune diseases is increased in the TS. Auto-immune dermatoses, such as pemphigoid gestationis, are one of the potential complications during pregnancy and should be known to practitioners.

Accelerated elimination from the circulation of homologous aged red blood cells in rats bearing anti-spectrin antibodies.

In order to analyse a possible role of anti-spectrin antibodies in the clearance of aged red blood cells (RBC), a homologous system was employed, whereby a population of aged RBC, obtained by hypertransfusion, was injected into rats bearing a high level of anti-spectrin antibodies, following immunization with spectrin. The aged RBC bound the anti-spectrin antibodies 'in vitro' and were eliminated from circulation in spectrin-treated rats at a faster rate than in control rats with naturally occurring antibodies. The analysis of the clearance curves revealed aged RBC of heterogeneous lifespans: two principal populations of short- and longer-living could be identified. In rats with anti-spectrin antibodies, the survival of the short-living population was further reduced. However, the similar kinetics of elimination of aged RBC in the two groups (with naturally-occurring and induced antibodies, respectively) suggest that anti-spectrin antibodies strengthened the intervention of the naturally-occurring ones. On the basis of these results, we assume that during their aging in circulation, RBC can accumulate surface alterations to make spectrin accessible to antibodies so that, in addition to anti-band 3 antibodies, anti-spectrin antibodies may contribute to their elimination.

Gamma-hydroxybutyric acid versus naltrexone in maintaining alcohol abstinence: an open randomized comparative study.

Maintaining abstinence from alcohol is the main goal in the treatment of alcohol dependence. Naltrexone (NTX) and gamma-hydroxybutyric acid (GHB) have proved able to maintain alcohol abstinence in alcoholic subjects. The aim of our study was to evaluate the efficacy of GHB compared with NTX in maintaining abstinence from alcohol after 3 months of treatment. A total of 35 alcohol-dependent outpatients were randomly enrolled in two groups: the GHB group consisted of 18 patients treated with oral doses of GHB (50 mg/kg of body weight t.i.d) for 3 months; the NTX group consisted of 17 patients treated with oral doses of NTX (50 mg/day) for 3 months. At the end of the study, a statistically significant difference (P=0.02) was found in the number of abstinent patients between the GHB and the NTX groups. In patients who failed to be abstinent, no relapses in heavy drinking were observed in the NTX group, while in the GHB group all patients relapsed. The results of the present study show that GHB is more effective than NTX in maintaining abstinence from alcohol in a short-term treatment period; on the other hand, NTX confirmed its ability to reduce alcohol relapses.

Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD).

OBJECTIVE: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes. OBJECTIVE: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD. DESIGN: Multicenter prospective study. PATIENTS: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin). MEASUREMENTS: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations. RESULTS: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P<0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P<0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P<0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P<0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P<0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P<0.025). CONCLUSIONS: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

Incidence of craving for and abuse of gamma-hydroxybutyric acid (GHB) in different populations of treated alcoholics: an open comparative study.

Gamma-hydroxybutyric acid (GHB) is a drug currently used for the treatment of alcohol dependence. The aim of our study was to investigate the incidence of craving for and abuse of GHB in 47 patients enrolled and divided into four groups: group A (pure alcoholics), group B (alcoholics with a sustained full remission from cocaine dependence), group C (alcoholics with a sustained full remission from heroin dependence) and group D (alcoholics in a methadone maintenance treatment [MMT] programme). All patients were treated with an oral dose of GHB (50 mg/kg of body weight t.i.d.) for three months. Craving for GHB was statistically significant higher in group B than in group A (P < 0.001), C (P = 0.01) and D (P < 0.001), and in group C than in group D (P < 0.05). Abuse of GHB proved to be statistically significant higher in group B than in group A (P < 0.001) and D (P < 0.01), and in group C than in group A (P = 0.01) and D (P < 0.05). Thus, the administration of GHB in alcoholics with a sustained full remission from heroin or cocaine dependence is not recommended; however, this should not discourage physicians from using GHB for the treatment of pure alcoholics or alcohol dependents following a MMT.

The clinical variability of maternally inherited diabetes and deafness is associated with the degree of heteroplasmy in blood leukocytes.

CONTEXT: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. OBJECTIVE: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. PARTICIPANTS: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. RESULTS: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA(1c) was also found and remained significant after adjustment for age at molecular sampling and gender. CONCLUSIONS: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.

Retinal and renal complications in patients with a mutation of mitochondrial DNA at position 3,243 (maternally inherited diabetes and deafness). A case-control study.

AIMS/HYPOTHESIS: We assessed the prevalence and determinants of retinal and renal complications in patients with maternally inherited diabetes and deafness (MIDD). METHODS: This was a multicentre prospective study comparing the prevalence of retinopathy and renal disease in 74 patients with MIDD and 134 control patients matched for sex, age and clinical presentation at onset of diabetes, duration of diabetes and current treatment. Comparisons were adjusted for HbA(1c) and hypertension. RESULTS: In MIDD patients, HbA(1c) (7.6 +/- 1.6 vs 8.5 +/- 2.0%, p < 0.002), systolic blood pressure (126.6 +/- 16.2 vs 133.1 +/- 17.3 mmHg, p < 0.007) and prevalence of hypertension (33.8 vs 64.2%, p < 0.0001) were lower than in control patients. Prevalence of diabetic retinopathy was 3.7-fold lower in MIDD patients (6/74, 8 vs 40/134, 29.6%, p < 0.0001). Differences between groups remained significant after adjustment for hypertension, systolic blood pressure and HbA(1c). In MIDD, urinary albumin excretion (314.8 vs 80.1 mg/24 h, p = 0.035) and creatinine plasma levels (103.5 vs 82.2 micromol/l, p = 0.0178) were higher and GFR was lower. Impaired renal function (GFR <60 ml/min) was four- to sixfold more frequent in MIDD. Differences between MIDD and control diabetic patients further increased when adjusted for HbA(1c) and systolic blood pressure (p < 0.0001). Adjustment for treatment with an ACE inhibitor or angiotensin II receptor antagonist did not modify the results. CONCLUSIONS/INTERPRETATION: This study indicates that diabetic retinopathy is less prevalent in MIDD than in control diabetes. This suggests that retinal alterations due to mitochondrial disease may have a protective role. By contrast, nephropathy is far more frequent in MIDD, suggesting the presence of a specific renal disease independent of diabetic nephropathy.

[Echographic evaluation of abscess pathology in superficial soft tissue. Personal experience]. / Valutazione ecografica della patologia ascessuale dei tessuti molli superficiali. Esperienza personale.

Sonography is currently considered a very useful technique for the study of inflammatory-abscess conditions in superficial soft tissues. The authors report their experience with US in the study of 22 patients. In 15 of them a comparison was made with X-ray findings, in 4 with fistulographic and in 2 with CT results. US allows the abscesses to be evaluated in both their morphological structure and anatomical topography. US has proven especially useful in correctly evaluating both complete and incomplete fistulas, as well as in revealing foreign bodies. The US pattern of an abscess often confirms clinical diagnosis for it supplies further and more accurate information. Moreover, US sometimes allows an abscess to be demonstrated even when the latter was missed at clinics. However, the differential diagnosis with malignant neoplasm is difficult and sometimes a decision can be made only by means of other diagnostic imaging modalities.