Buchbesprechungen

Ohne Zusammenfassung     

Buchbesprechungen

Ohne Zusammenfassung     

The D313Y variant in the GLA gene – no evidence of a pathogenic role in Fabry disease

Fabry disease is an X- linked inherited lysosomal storage disease caused by mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A (α-Gal A). The possible pathological significance of the D313Y variant in the GLA gene has not been verified and it may be a Fabry variant. Our aim was to elucidate whether the presence of the D313Y variant influenced the α-Gal A activity or resulted in Fabry symptoms or Fabry organ involvement. In two Danish families the presence of the D313Y variant did not result in reduced α-Gal A activity or clinical Fabry manifestations in males, and the presence in Fabry females did not significantly enhance the phenotype of a known causative mutation in the GLA gene (G271S). Our findings indicate that the D313Y variant is not causative to nor enhancing Fabry disease phenotype. The D313Y variant in the GLA gene was not disease causative in 2 Danish families. Investigating male family members were crucial in excluding the Fabry phenotype, and thus very important for proper genetic counceling of all family members, as well as overdiagnosing a devastating genetic disease.     

Vitamin E and depressive symptoms are not related. The Rotterdam Study

OBJECTIVE: To investigate the reported association between low vitamin E levels and depressive symptoms in a population-based study. METHODS: The study is based on a cohort of 3884 adults aged 60 years and over who participated in the third survey of the Rotterdam Study, were screened for depressive symptoms with the Center of Epidemiological Studies Depression Scale and from whom blood was drawn. All screen-positive subjects had a psychiatric work-up. Blood levels of vitamin E were compared between 262 cases with depressive symptoms and 459 randomly selected reference subjects. All analyses were stratified by sex, and adjusted for age, cholesterol, cognitive score, smoking, dietary supplement use, marital status, living alone, and functional disability score. RESULTS: Vitamin E levels in men with depressive symptoms were lower than in non-depressed men after adjusting for age, whereas no such difference was found in women. This association in men was substantially weakened after controlling for biological factors, and disappeared with additional adjustment for nutritional behaviour and social factors. No differences were observed when the analyses were restricted to cases with depression as defined in the Diagnostic and Statistical Manual of Mental Disorders IV. CONCLUSIONS: After control for several biological and behavioural factors relating to health we found no association between low vitamin E levels and depressive symptoms or depression in the elderly.     

A rare presentation of cardiac amyloid deposits isolated to intramural vessels

The present case illustrates the diagnostic challenges in symptomatic patients with heart failure of unknown etiology. The patients were previously diagnosed with κ‐light chain amyloidosis without cardiac involvement. Echocardiography showed heart failure with mildly reduced ejection fraction but no signs of amyloidosis. Coronary angiogram showed normal arteries and 11C‐PIB positron emission tomography was negative for amyloid deposits. Exercise testing revealed severe heart failure and reduced coronary flow velocity reserve. Endomyocardial biopsies showed amyloid in the intramural coronary arteries without interstitial amyloid deposits. Hence, the patient was diagnosed with microvascular dysfunction‐induced heart failure due to vessel wall amyloidosis.     

Clinical comparison of extracorporeal piezoelectric lithotripsy (EPL) and intracorporeal electrohydraulic lithotripsy (EHL) in difficult bile duct stones

Today, nearly 90% of common bile duct stones are extracted endoscopically. Problems are encountered if there are large stones or a duct stenosis. Extracorporeal piezoelectric lithotripsy (EPL) as well as intracorporeal electrohydraulic lithotripsy (EHL) serve as an alternative to surgical intervention for those few patients in whom endoscopic measures have failed. A total of 35 patients with common bile duct stones in whom conventional endoscopic treatment had failed were selected on the condition that stone visualization through ultrasound was possible and that the papilla was within easy reach of the endoscope. Patients fulfilling the inclusion criteria were randomly treated either by EPL or EHL. The average age of our patients was 73 years. The main reasons for failure of conventional endoscopy were due to the large size of the stones (13 patients), impacted stones (16), or the presence of a biliary stricture (6). In the EPL group, visualization of the stones by ultrasound and ensuing treatment were possible in 16 of 18 patients (89%); stones could be fragmented in 15 patients. In 13 patients, the biliary tree could then be completely freed of calculi; the success rate was 72% for all the patients (13 of 18). On average, the patients had 2.3 treatments on the lithotripter, and 3870 shock waves were applied per treatment. In the EHL group stones were successfully fragmented in 13 of 17 patients (76.5%). The average number of treatments was 1.4. Comparing both therapies, there was no difference in stone-free rates. In both groups, additional endoscopic interventions were necessary to clear the bile duct. The mean number of lithotripsy sessions was less in the EHL group (1.4 vs 2.3). There were no major differences in average hospital stay, 30-day mortality was zero in both groups. Combined treatment including EPL, EHL, and intracorporeal laser lithotripsy was finally successful in 32 patients (91.5%). It is concluded that EHL might be the method of choice for smaller, single stones in the more proximal parts of the common bile duct. In these cases, complete duct clearance in one lithotripsy session can be achieved. Multiple and large stones are probably best accessible to EPL. With a combination of the methods described, the bile duct can be cleared of concrements in almost every instance. As a result, surgery for choledocholithiasis has become the absolute exception.This work was presented in part at the 1993 Annual Meeting of the american Gastroenterological Association in Boston and published in abstract form (Gastroenterology 104:A347, 1993).     

Postnatal confirmation of prenatally diagnosed trisomy 20 mosaicism in a patient with linear and whorled nevoid hypermelanosis

Linear and whorled nevoid hypermelanosis (LWNH) is characterized by hyperpigmented reticulate macules in a Blaschko linear arrangement without atrophy or preceding inflammation. Underlying chromosomal mosaicism was often assumed, but has been verified in only a few published cases. We report a 7-year-old boy with LWNH associated with congenital ventricular septal defect and psychomotor retardation. Prenatal chromosomal analysis of amniocytes revealed trisomy 20 mosaicism, which was not confirmed in peripheral blood lymphocytes after birth. Histologic sections of skin biopsy specimens taken at age 6 years showed hyperpigmentation of the basal epidermal layer with prominent melanocytes and isolated melanophages in the upper dermis. Cytogenetic analysis of cultured skin fibroblasts revealed an extra chromosome 20 in 5 of the 30 metaphases studied (17%). Mosaic trisomy 20 is one of the most common autosomal mosaicisms identified in amniocytes and is, as a rule, compatible with normal pregnancy outcome. In postnatal analysis of peripheral blood lymphocytes, an extra chromosome 20 could never be detected. However, when confirmed in skin fibroblasts, trisomy 20 mosaicism may be associated with systemic anomalies. The present case shows for the first time an association of LWNH with trisomy 20 mosaicism and emphasizes the importance of analyzing skin fibroblasts in cases of prenatally diagnosed trisomy 20.     

Quantitative magnetic resonance spectroscopy at 3T based on the principle of reciprocity

Quantification of magnetic resonance spectroscopy signals using the phantom replacement method requires an adequate correction of differences between the acquisition of the reference signal in the phantom and the measurement in vivo. Applying the principle of reciprocity, sensitivity differences can be corrected at low field strength by measuring the RF transmitter gain needed to obtain a certain flip angle in the measured volume. However, at higher field strength the transmit sensitivity may vary from the reception sensitivity, which leads to wrongly estimated concentrations. To address this issue, a quantification approach based on the principle of reciprocity for use at 3T is proposed and validated thoroughly. In this approach, the RF transmitter gain is determined automatically using a volume‐selective power optimization and complemented with information from relative reception sensitivity maps derived from contrast‐minimized images to correct differences in transmission and reception sensitivity. In this way, a reliable measure of the local sensitivity was obtained. The proposed method is used to derive in vivo concentrations of brain metabolites and tissue water in two studies with different coil sets in a total of 40 healthy volunteers. Resulting molar concentrations are compared with results using internal water referencing (IWR) and Electric REference To access In vivo Concentrations (ERETIC). With the proposed method, changes in coil loading and regional sensitivity due to B₁ inhomogeneities are successfully corrected, as demonstrated in phantom and in vivo measurements. For the tissue water content, coefficients of variation between 2% and 3.5% were obtained (0.6–1.4% in a single subject). The coefficients of variation of the three major metabolites ranged from 3.4–14.5%. In general, the derived concentrations agree well with values estimated with IWR. Hence, the presented method is a valuable alternative for IWR, without the need for additional hardware such as ERETIC and with potential advantages in diseased tissue.