Bone status and fractures in 85 adults with Wilson's disease.

UNLABELLED: Wilson's disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures. INTRODUCTION: Wilson's disease (WD) is characterized by copper deposition, especially in the liver and central nervous system. Two studies showed a high prevalence of osteoporosis in WD patients. We wanted to assess the prevalent fractures and bone mineral density (BMD) and to identify risk factors for bone loss and fractures in a large group of WD patients. METHODS: In this prospective cross-sectional survey at National center of reference for WD, we included 85 patients, 47 women, and 38 men, with a mean age of 35 ± 10 years, and mean time from diagnosis to study of 21 ± 9 years; 57 (67%) patients had neurological signs. Peripheral fractures, prevalent radiological vertebral fractures (VFx), and dual-energy X-ray absorptiometry BMD measurements at the femoral neck (FN) and lumbar spine (LS) were studied. RESULTS: Mean LS and FN Z-score was normal (-0.37 ± 1.20 at LS and -0.06 ± 1.20 at FN). BMI <19 kg/m(2) and amenorrhea were associated with low BMD. Prevalent peripheral fractures were noted in 43 (51%) and VF in 7 (8%) patients. Severity of neurological involvement and male sex was associated with peripheral fractures, whereas older age, severe neurological involvement, and low BMD and Z-score values were associated with VF. CONCLUSION: Our data showing normal BMD overall do not support routine bone status evaluation in adults with WD. However, patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk factors for fractures and may require specific monitoring.

Corpus callosum abnormalities in Wilson's disease.

INTRODUCTION: Wilson's disease (WD) with neurological presentation is associated with brain lesions classically localised in globus pallidus, putamen, thalamus, mesencephalon, pons and dentate nucleus. Lesions of corpus callosum (CC) have not been studied in a broad population of patients with WD. OBJECTIVE: Evaluation of the frequency of CC lesions in patients with neurological symptoms related to WD. METHOD: The authors included all patients with neurological expression of WD, followed in the French national centre for WD who had a brain MRI between March 2006 and December 2008. The localisation of brain lesions was analysed and the frequency of lesions in CC evaluated. All patients were assessed using the Unified Wilson's Disease Rating Scale. For patients with abnormalities located in CC, a clinical dysconnexion syndrome was investigated. RESULTS: Among 81 patients (45 men, mean age: 34.8 years, from 12 to 74 years) with neurological expression, 42% had white-matter lesions on fluid-attenuated inversion recovery MRI. 23.4% of patients presented CC lesions, limited to the posterior part (splenium). The severity of disability estimated by Unified Wilson's Disease Rating Scale was correlated with the presence of CC lesions on MRI. CONCLUSION: Abnormalities in CC are not unusual (23.4%). Together with lesions of basal ganglia, CC signal changes should suggest the diagnosis of WD.

[Abnormal copper metabolism in adult]. / Anomalies du métabolisme du cuivre chez l'adulte.

Copper is essential for many enzymatic reactions and in neurotransmitter biosynthesis. Its deficiency or its excess has consequences on many organs, especially the liver and the brain. The biochemical tests performed in case of suspicion of copper metabolism disorder are difficult to analyse. They include the measurement of serum ceruloplasmin, serum copper and 24h urinary copper excretion. The interpretation must take into account the clinical features. We distinguish mainly: (1) copper deficiency, acquired in malabsorption or in copper diet deficiency, or related to a genetic disease (Menkes disease); (2) copper overload, acquired or from a genetic origin (Wilson disease); (3) aceruloplasminemia, reducing ferroxidase activity leading to iron overload. It is important to diagnose these diseases as some of them have an effective treatment if it is started early enough.

Ubiquitination precedes internalization and proteolytic cleavage of plasma membrane-bound glycine receptors.

The inhibitory glycine receptor (GlyR) in developing spinal neurones is internalized efficiently upon antagonist inhibition. Here we used surface labeling combined with affinity purification to show that homopentameric alpha1 GlyRs generated in Xenopus oocytes are proteolytically nicked into fragments of 35 and 13 kDa upon prolonged incubation. Nicked GlyRs do not exist at the cell surface, indicating that proteolysis occurs exclusively in the endocytotic pathway. Consistent with this interpretation, elevation of the lysosomal pH, but not the proteasome inhibitor lactacystin, prevents GlyR cleavage. Prior to internalization, alpha1 GlyRs are conjugated extensively with ubiquitin in the plasma membrane. Our results are consistent with ubiquitination regulating the endocytosis and subsequent proteolysis of GlyRs residing in the plasma membrane. Ubiquitin-conjugating enzymes thus may have a crucial role in synaptic plasticity by determining postsynaptic receptor numbers.

[Residues of ethylene chlorohydrin (ECH) in infusions of cocoa and in chocolate (author's transl)]. / Restmengen von Ethylenchlorhydrin (ECH) in Kakaotrunk und Schokolade.

With a sensitive method residues of 0.2--0.6 ppm ECH are found in commercial and bendtop infusions of cocoa and 1.8--5.6 ppm ECH in chocolate. The balance is established with time between ECH and ethylene oxide (EO) in the boiling infusion and the distillate depending on time. It is found that the ECH concentration in the infusion is reduced in 15 min to 1/7 by evaporation alone. No reaction to EO or ethylene glycol or other metabolites is detectable. For the determination alkali is added to the sample, followed by distillation of any formed EO into dilute sulfuric acid, where ethylene glycol is oxidized to formaldehyd according to Malaprade. This is distilled off for further enrichment and determined according to Bremanis by photometry at 570 nm. The determination for limit was to 0.01 ppm, the standard deviation is s = 0.0034 ppm (N = 30), the yield 99.8%. The sensitivity may be increased tenfold by increasing sample size.