Genetic and biochemical approach to early prenatal diagnosis in a family with mut methylmalonic aciduria

Genetic and biochemical prenatal diagnosis was performed at 11 weeks of gestation in a family with a proband affected by mut methylmalonic aciduria (MMA) and homozygotes for the MUT gene c.643G>A (p.Gly215Ser) mutation. Both chorionic villus and amniotic fluid samples were used. The presence of high levels of methylmalonic acid and propionylcarnitine determined by gas chromatography/mass spectrometry and LC/MS/MS analysis, respectively, and the identification of the p.Gly215Ser at a homozygous level in foetal DNA allowed a certain, rapid and early diagnosis. To our knowledge, this is the first mut MMA prenatal diagnosis carried out by genetic and biochemical approach.     

Sweet's Syndrome associated with Hodgkin's disease: case report

Sweet's syndrome is a rare cutaneous disease of unknown etiology. About 20% of the cases are associated with hematological neoplasms, and cases related with Hodgkin's disease are rare. We present the case of a 57-year old male patient who developed the syndrome concomitantly with the neoplasm. The diseases were controlled with specific treatment.     

Difficulties in diagnosing slowly progressive mucopolysaccharidosis VI: A case series

An Erratum for this article can be found here: http://iospress.metapress.com/content/e16437020701m0u5/?p=df8dd6709cf44367a0c0e5d917aaeddf&pi=11We describe the cases of two adult sisters recently diagnosed with the attenuated form of mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome). MPS VI is a rare, clinically heterogeneous lysosomal storage disorder that is characterized by a deficiency in the glycosaminoglycan-degrading enzyme arylsulfatase B. Both cases had been misdiagnosed for over 30 years despite the presence of several characteristics of the disease, including short stature (mild), coarse facial features, skeletal dysmorphisms, carpal tunnel syndrome, heart valve disease, and spinal cord compression, which together are suggestive of a lysosomal storage disease. Awareness about the clinical features of MPS VI should be communicated amongst treating neurologists, rheumatologists and other specialists who are involved in the healthcare decisions of these patients with presenting symptoms, so they can refer them to specialized centers for proper diagnosis and treatment.     

Recombinant LH administration in subsequent cycle after “unexpected” poor response to recombinant FSH monotherapy.

Poor ovarian response (POR) is most frequently linked to the condition known as diminished ovarian reserve, but it can also occur in the absence of pathological ovarian reserve tests (“unexpected” POR). Because possible explanations include theca cells function deficiency, our aim was to evaluate the effect of r-LH administration in “unexpected” poor responders.

A retrospective, single-centre, cohort study was conducted on 65 patients with AMH >0.5?ng/ml and/or AFC >5 with POR in their first cycle. Patients underwent a second IVF cycle with same protocol (long- or antagonist) and same starting dose of r-FSH used in the first cycle, plus daily addiction of 150?IU of r-LH from day 1.

Compared to the first cycle, r-LH addition in the second cycle determined an increase in number of oocytes retrieved (p?p?2 levels at hCG triggering (p?p?=?0.002). A 15% clinical pregnancy rate was also observed in the second cycle.

Our results suggest that patients with non-pathological ovarian reserve tests and previous “unexpected” POR seem to benefit from r-LH addition in subsequent cycles without the need to increase the r-FSH starting dose, possibly due to an underlying occult theca cells deficiency.     

Nitric Oxide concentration in endometrial washing throughout the menstrual cycle

Purpose  

Nitric oxide (NO) intrauterine production has been shown to have an important role in the reproductive system in females. The objective of the present study was to evaluate NO concentration in endometrial washing throughout the menstrual cycle.     

Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle-stimulating hormone starting dose in in vitro fertilisation cycles

Please cite this paper as: La Marca A, Papaleo E, Grisendi V, Argento C, Giulini S, Volpe A. Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle-stimulating hormone starting dose in in vitro fertilisation cycles. BJOG 2012;119:1171-1179. Objective To elaborate a nomogram based on markers of ovarian reserve for the calculation of the appropriate starting dose of follicle-stimulating hormone (FSH). Design Cohort study of infertile women. Setting In vitro fertilisation (IVF) unit, University Hospital of Modena, Italy. Population Women aged 18-40?years (n?=?346) and undergoing their first IVF cycle. Methods Serum FSH and anti-Müllerian hormone (AMH) measurement. Main outcome measures Development of a model for the prediction of ovarian response to FSH. Results A model based on age, AMH and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting FSH dose <225?IU in 55.1 and 25.9% of women younger and older than 35?years, respectively. Conclusions In the present study we clearly demonstrated that the daily FSH dose may be calculated on the basis of a woman's age and two markers of ovarian reserve, namely AMH and FSH, with the first two vari;s (age and AMH) being the most significant predictors. The nomogram we developed seems easily applicable for clinicians during their daily clinical practice.     

Pelvic radiation disease: Updates on treatment options

Pelvic cancers are among the most frequently diagnosed neoplasms and radiotherapy represents one of the main treatment options. The irradiation field usually encompasses healthy intestinal tissue, especially of distal large bowel, thus inducing gastrointestinal (GI) radiation-induced toxicity. Indeed, up to half of radiation-treated patients say that their quality of life is affected by GI symptoms (e.g., rectal bleeding, diarrhoea). The constellation of GI symptoms - from transient to long-term, from mild to very severe - experienced by patients who underwent radiation treatment for a pelvic tumor have been comprised in the definition of pelvic radiation disease (PRD). A correct and evidence-based therapeutic approach of patients experiencing GI radiation-induced toxicity is mandatory. Therapeutic non-surgical strategies for PRD can be summarized in two broad categories, i.e., medical and endoscopic. Of note, most of the studies have investigated the management of radiation-induced rectal bleeding. Patients with clinically significant bleeding (i.e., causing chronic anemia) should firstly be considered for medical management (i.e., sucralfate enemas, metronidazole and hyperbaric oxygen); in case of failure, endoscopic treatment should be implemented. This latter should be considered the first choice in case of acute, transfusion requiring, bleeding. More well-performed, high quality studies should be performed, especially the role of medical treatments should be better investigated as well as the comparative studies between endoscopic and hyperbaric oxygen treatments.     

Is ESES/CSWS a strictly age-related disorder?

OBJECTIVES: We report on a case of ESES/CSWS observed in a patient of 21 years and still persisting at the age of 25. Cases of ESES/CSWS have never been previously described in adult patients. ESES/CSWS is considered to be related to the degree of maturation of the central nervous system, and therefore strictly age-related. METHODS: Our case of ESES/CSWS was observed in a 2 1 year old woman referred for cognitive and behavioral disorders. She had previously had epileptic fits, but was seizure free at that time. The patient underwent a full-night polygraphic recording , which showed typical ESES/CSWS pattern, with a Spike-and-Wave Index >8 5%. Polysomnography was repeated 9 times in a 4 year follow-up, during which the ESES/CSWS condition persisted, despite the pharmacological treatments. The patient also underwent cerebral magnetic resonance imaging and fludeoxyglucose F 18 positron emission tomography (PET). RESULTS: The PET study revealed reduced metabolic activity within the lower gyrus of the right parietal lobe, but no significant difference between subcortical structures and cortical mantle was seen. MRI scans were normal. CONCLUSIONS: This observation suggests that ESES/CSWS might not always be an age-related condition. Sleep EEG recordings should always be performed in patients with behavioral disorders and a history of epileptic fits.     

Anti-Müllerian hormone-based prediction model for a live birth in assisted reproduction

Prediction of assisted reproduction treatment outcome has been the focus of clinical research for many years, with a variety of prognostic models describing the probability of an ongoing pregnancy or a live birth. This study assessed whether serum anti-Müllerian hormone (AMH) concentrations may be incorporated into a model to enhance the prediction of a live birth in women undergoing their first IVF cycle, by analysing a database containing clinical and laboratory information on IVF cycles carried out between 2005 and 2008 at the Mother-Infant Department of University Hospital, Modena. Logistic regression was used to examine the association of live birth with baseline patient characteristics. Only AMH and age were demonstrated in regression analysis to predict live birth, so a model solely based on these two criteria was generated. The model permitted the identification of live birth with a sensitivity of 79.2% and a specificity of only 44.2%. In the prediction of a live birth following IVF, a distinction, however moderate, can be made between couples with a good and a poor prognosis. The success of IVF was found to mainly depend on maternal age and serum AMH concentrations, one of the most relevant and valuable markers of ovarian reserve.