Epidemiology, clinical features, and mortality rate of Wilson disease in Moroccan children: A pediatric case series.

BACKGROUND AND STUDY AIMS: Wilson's disease is an autosomal recessive disorder, that affects copper metabolism, leading to copper accumulation in the liver, nervous system, and cornea. Data are lacking on the epidemiology, the clinical and laboratory characteristics, treatment, and survival of Wilson's disease in Morocco. The aim of this study was to examine these features and the cause of death in a Moroccan pediatric population. PATIENTS AND METHODS: The study was carried out at the University Hospital Center of Marrakesh, Morocco; 46 children were diagnosed with Wilson's disease from 2008 to 2019. The diagnosis was based on low serum ceruloplasmin, increased urinary copper concentrations, the presence of Kayser-Fleischer rings, a family history of Wilson's disease, and a Leipzig score of ≥ 4. RESULTS: A total of 42 patients were referred to the center for hepatic or neurological manifestations; four patients were asymptomatic. Consanguineous marriage was found in 67.4% of the cases. The mean duration of illness (42 patients) was 4.9 ± 3.9 years. Kayser-Fleischer rings were found in 60.9% of 46 patients. Of the 42 symptomatic patients: 28 of 30 (93.3%) patients had low serum ceruloplasmin (<0.2 g/L), and 24 h urinary copper >100 µg/day was found in 34 of 35 (97.1%) cases. The treatment was established with D-penicillamine for 43 of the 46 patients, with zinc acetate for one patient and with zinc sulfate in for one patient, while one patient was not treated. D-penicillamine was discontinued in nine patients because of adverse effects such as thrombocytopenia, neurological deterioration, pancytopenia, severe vomiting and severe hypersensitivity. In total 28 patients were clinically and biologically stabilized, two patients experienced vision loss, and 16 patients died (38%). The main cause of death was diagnosis made at an advanced stage of disease and stopping treatment. CONCLUSION: Wilson's disease is a rare condition associated with treatement efficacy, but late diagnosis and stopping treatment can lead to a high mortality rate.

Coastal sedimentation across North America doubled in the 20th century despite river dams.

The proliferation of dams since 1950 promoted sediment deposition in reservoirs, which is thought to be starving the coast of sediment and decreasing the resilience of communities to storms and sea-level rise. Diminished river loads measured upstream from the coast, however, should not be assumed to propagate seaward. Here, we show that century-long records of sediment mass accumulation rates (g cm-2 yr-1) and sediment accumulation rates (cm yr-1) more than doubled after 1950 in coastal depocenters around North America. Sediment sources downstream of dams compensate for the river-sediment lost to impoundments. Sediment is accumulating in coastal depocenters at a rate that matches or exceeds relative sea-level rise, apart from rapidly subsiding Texas and Louisiana where water depths are increasing and intertidal areas are disappearing. Assuming no feedbacks, accelerating global sea-level rise will eventually surpass current sediment accumulation rates, underscoring the need for including coastal-sediment management in habitat-restoration projects.

Serum copper, zinc and selenium levels in Tunisian patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder. The etiology of this disease is still not fully clear, but free radicals have been proposed to cause neuronal injury. Metals play a key role in the intracellular oxidative balance. However their implication in the degeneration process remains unknown. AIM: To assess Cu, Zn and Se concentrations in serum of a group of PD patients in order to determinate, in comparison with age-matched controls, whether alteration in their levels could be involved in PD. METHODS: A serum level of 3 trace elements (Cu, Zn and Se) was investigated in 48 patients with PD and 36 matched controls using plasma atomic absorption spectrometry. We compared these parameters in PD patients with controls, and we also compared the variations within the PD group according to age, illness duration, stage of the disease and levodopa intake. RESULTS: Patients with PD had significantly lower Cu levels compared to controls. The mean Zn and Se levels in PD patients did not differ significantly from those of controls. Levodopa therapy, age, stage, and illness duration did not significantly influence the measured parameters. CONCLUSION: These results suggest that a disturbance of the plasmatic rate of Cu could be a marker of PD or at least, a risk factor for the development of this disease. Although zinc participates to the reduction of oxidative stress and the antioxidant role of the selenium, their implication in the onset of PD is not clearly established. Perspectives for the future could include antioxidant therapy. For this reason, other prospective studies should be conducted on this subject to elucidate the implication of trace elements in PD.

[Diagnosis and care of Wilson disease with neurological revelation]. / Maladie de Wilson, penser aux formes neurologiques chez l'enfant.

Wilson disease is an autosomal recessive disease that produces a copper accumulation in many organs, initially in the liver, progressing to liver cirrhosis, and in the brain, with different neurologic symptoms. Diagnosis is based on clinical, biochemical, and genetic tests. Different treatments based on chelating agents may help reduce the disease's spontaneous morbidity and mortality. We describe three patients who presented Wilson disease before 18 years of age, with initial neurologic symptoms between 1998 and 2010. After comparison with literature reports, their clinical symptoms, progression, and care allowed us to propose a treatment algorithm. Neurologic symptoms are present in 35% of the patients with Wilson disease such as dystonia, extrapyramidal syndrome, dysarthria, dysphagia, and psychiatric symptoms. The time to diagnosis remains too long and may account for the increased severity of the illness encountered and problems treating these patients. The first treatment choice must be triethylenetetramine, which causes fewer side effects of initial worsening of symptoms compared to D-penicillamine. Zinc therapy is the first treatment for asymptomatic patients or those on maintenance treatment. Finally, liver transplantation is a potential treatment even if the patient presents severe neurological disability because it may improve clinical symptoms. However, further research is warranted on this matter.

Protective role of selenium supplementation against cardiac lesions induced by the combination of levomepromazine and risperidone in the rabbit.

Neuroleptics are a suspected cause of sudden death in psychiatric patients, especially in those with pre-existing cardiac lesions. As these lesions were previously shown to be associated with selenium (Se) deficiency, the aim of the present study was to evidence the possible protective effect of Se supplementation against cardiac lesions induced by the combination of the neuroleptic drugs levomepromazine and risperidone in the rabbit. Two groups of 6 rabbits were treated with 3 mg/kg of levomepromazine daily intramuscularly combined with 1 mg/kg of risperidone intramuscularly every other week for 3 consecutive months, and one group additionally received a solution of sodium selenite (2 microg/kg/day) intramuscularly during the whole treatment period. Furthermore, one group of six untreated animals was given the Se supplementation and another group of six control animals received saline daily. Blood samples were drawn before and at the end of the treatment period for the measurement of serum Se levels. At the end of the study, all animals were sacrificed and their hearts were removed for the measurement of tissue Se concentrations. In addition, the hearts were prepared for histopathological examination. A variety of cardiac lesions was found in the neuroleptics-treated animals without supplementation and to a lesser extent in the control and Se-supplemented untreated animals. Importantly, only rare cardiac lesions were observed in neuroleptics-Se-treated animals. The most striking differences in Se concentrations were noted in the myocardium: as compared to controls, there was a 43% reduction in neuroleptics-treated, but non-Se-supplemented animals (p < .01), at the end of the treatment period, whereas only a 14% reduction (p < .05) was noted in the neuroleptics-Se-treated animals. These results confirm that neuroleptics induce cardiac lesions associated with Se deficiency. Selenium supplementation markedly decreased the incidence and severity of neuroleptics-induced cardiac lesions and these findings may serve as a basis for further evaluation of the protective role of Se supplementation in neuroleptics-treated patients. However, Se supplementation in normal animals without Se deficiency was also shown to be cardiotoxic.

Effect of supplementation with Se-enriched yeast and factors influencing Se concentration in plasma of transplant recipients.

The aim of this study was to assess the bioavailability of selenium (Se) in Se-enriched yeast and the possible impact of age, sex and area of residence on the Se concentration in plasma in 179 transplant recipients, as Se clinical effects in the prevention of cutaneous epithelial lesions in organ transplant recipients has been reported elsewhere. Subjects were randomized to receive either 200 microg Se/day (group 1:91 patients) or placebo (group 2: 88 patients) for 3 years. Plasma Se levels were measured at the beginning of the study and after 4, 12, 24 and 36 months of Se or placebo supplementation. Initial plasma Se levels were 90.9+/-26.1 microg/L for placebo and 94.0+/-25.3 microg/L for Se-supplemented groups. At baseline, the Se level was not linked to sex and age but to area of residence, although the number of subjects in each area was insufficient to draw any conclusions. Plasma Se levels were statistically lower in cases of liver transplant compared to kidney and heart transplant (p=0.03). Over the 3-year period of supplementation, plasma Se in the supplemented subjects was significantly higher than in the placebo group (p<0.01) and there was an interaction (p<0.01) between supplementation and time for plasma Se. Supplementation with Se-enriched yeast significantly increased the Se concentration in plasma of the patients to a plateau: the mean plasma Se of the Se-supplemented patients increased to 164.7+/-35.8 microg/L at 4 months and then remained similar at 12 (176.1+/-48.3 microg/L), 24 (176.1+/-54.2 microg/L) and 36 (182.2+/-46.4 microg/L) months.

Long-term results of liver transplantation for Wilson's disease.

UNLABELLED: Wilson's disease is a hereditary defect in hepatic copper metabolism, causing hepatic, neurological and/or psychiatric manifestations. For patients with severe disease, liver transplantation is the treatment of choice. The aim of this study was to report the long-term outcome of patients who underwent liver transplantation for Wilson's disease. PATIENTS AND METHODS: Thirteen patients with Wilson's disease, transplanted in Lyon France between January 1987 and May 2006, were including in this study: eight women and five men, aged eight to 53 years (median 20 years, seven children and six adults). The diagnosis of Wilson's disease was established before liver transplantation. RESULTS: The indication for liver transplantation was chronic (69%) or fulminant liver failure (31%). The median follow-up after liver transplantation was 10 years with 100% patient survival. Copper metabolism returned to normal in all patients. None of the patients with exclusive liver disease required chelation treatment after liver transplantation and none developed neurological symptoms of Wilson's disease. CONCLUSION: Liver transplantation totally reverses the abnormalities of copper metabolism and subsequent hepatic failure, but the course of neurological symptoms remains unpredictable. Long-term patient survival can be excellent without occurrence of neurological complications.

Role of selenium in heart lesions produced by neuroleptics in the rabbit.

Organic and/or functional heart lesions sometimes resulting in sudden death have been described in psychiatric patients treated with neuroleptics. As selenium has been suggested previously to play a role in the development of such lesions, the present study was undertaken to determine whether a correlation could be found between heart lesions induced by neuroleptics and changes in blood selenium as well as myocardial tissue concentrations in the rabbit. Twelve NZW adult rabbits were treated intramuscularly with both levomepromazine (3 mg kg(-1) day(-1)) and risperidone (1 mg kg(-1) once every other week) for 3 months, and compared with 12 saline-treated controls. Blood samples were drawn before and at the end of the study. Tissue samples from the heart, liver and kidneys were obtained at the end of treatment, and the hearts were examined histologically. Heart lesions including disorganization of cardiac fibers, myolysis, interstitial and endocardial fibrosis, and necrosis were noted in treated animals, but not in controls. There was a 20% decrease in selenium blood levels and a 50% decrease in selenium myocardial tissue levels in treated animals compared with controls (P < 0.001). In contrast, no differences in selenium levels in liver and kidneys were found across the experimental groups. These results suggest a possible correlation between selenium depletion and neuroleptics-induced heart lesions.

Peripheral blood markers of oxidative stress in Parkinson's disease.

Oxidative stress and generation of reactive oxygen species are believed to be implicated in Parkinson's disease (PD). Erythrocyte activity of superoxide dismutase (SOD) and catalase, the blood glutathione system, and plasma levels of thiobarbituric-acid-reactive substances (TBARS) were measured in 80 PD patients. These biochemical parameters were also measured in 29 age-matched controls. Patients with PD had significantly higher red blood corpuscle (RBC) activity of SOD. The mean RBC activity of catalase in PD patients did not differ significantly from those of controls. RBC catalase activity was significantly lower in advanced cases of PD compared to early cases. Oxidized glutathione was significantly higher in RBCs of PD patients, although there were no changes in total glutathione and reduced glutathione compared to controls. TBARS content was increased in patients with PD. Levodopa therapy, age and duration of illness did not significantly influence the measured parameters. Our study supports the previous hypothesis that oxidative stress is implicated in the pathogenesis of PD. Perspectives for treatment of PD in the future could include antioxidant therapy.

Bilateral anorchia in infancy: occurence of micropenis and the effect of testosterone treatment.

OBJECTIVE: To analyze the clinical and histological findings in boys with bilateral anorchia and the response to testosterone treatment on penis length. STUDY DESIGN: Patients were divided into two groups according to the absence (group A, n = 29) or the presence (group B, n = 26) of palpable intrascrotal or inguinal mass at first clinical examination. RESULTS: A micropenis was found in 46% of patients (n = 24) with a similar proportion in both groups. Testosterone treatment induced a mean penis length gain of 1.9 +/- 1.3 SDS (standard deviation score). However, micropenis persisted in six patients. Histological examination (n = 18) confirmed the absence of any testicular structure with deferent ducts being present unilaterally or bilaterally in all but three patients. In these three patients, a hemorrhagic testis, probably as a result of a mechanical torsion, was found. CONCLUSIONS: The presence of isolated micropenis in almost half of patients with bilateral anorchia strongly suggests that the testicular damage frequently occurs during the second half of gestation after male sexual differentiation. In most cases, testosterone treatment stimulates the penile growth. Although the pathogenesis of bilateral anorchia may be heterogeneous, our study suggests that gonads may have been functionally abnormal before they disappeared, and suggests that some patients have an intrinsic endocrine disorder.

[Wilson disease: clinical and biological aspects]. / La maladie de Wilson: aspects clinicobiologiques.

Wilson disease is an autosomal recessive disorder of copper excess. This illness results from mutations of the ATP7B gene (chromosome 13, MIM# 277900). The discovery of the gene allowed a better understanding of cytosolic copper trafficking and its relationship with ceruloplasmin synthesis. Symptomatic patients may present with hepatic, neurologic or psychiatric forms. Clinical and phenotypic evidences provide only presumptive arguments for this disease which can be routinely assessed by molecular analysis. This genetic disease which can be efficiently treated was formerly biologically suspected after a careful but sometimes invasive study of copper metabolism. Genetic advances can now give a definite answer using linkage analysis and research for disease-causing mutations. However, this diagnosis strategy is limited since currently over 320 mutations and 80 polymorphisms have been currently identified.

Structural and functional abnormalities of large arteries in the Turner syndrome.

OBJECTIVE: To analyse the structural and functional abnormalities in the large arteries in women with the Turner syndrome. METHODS: Aortic stiffness (assessed by means of the carotid femoral pulse wave velocity), level of amplification of the carotid pressure wave (by applanation tonometry), and carotid remodelling (by high resolution ultrasound) were studied in women with the Turner syndrome. Clinical and ambulatory blood pressures were taken into account in the analysis. Thus, 24 patients with the Turner syndrome and 25 healthy female subjects matched for age were studied. RESULTS: Women with the Turner syndrome had a higher augmentation index than the controls (Turner, mean (SD) 0.04 (0.14) v controls, -0.14 (0.13), p < 0.001) but a lower peripheral pulse pressure (39 (8) mm Hg v 47 (11) mm Hg, p = 0.010 in the clinic; 44 (5) mm Hg v 47 (6) mm Hg, p = 0.036 during the 24 hour ambulatory recording). The luminal diameter of the common carotid artery and the carotid-femoral pulse wave velocity were similar in the two groups, whereas carotid intima-media thickness tended to be higher in women with the Turner syndrome (0.53 (0.06) mm v 0.50 (0.05) mm, p = 0.06). After correction for body surface area, carotid intima-media thickness and pulse wave velocity were higher in women with the Turner syndrome. CONCLUSIONS: Vascular abnormalities observed in the Turner syndrome are implicated in the origin of the cardiovascular complications that occur in this syndrome. These abnormalities are morphological but also functional. An increase in the augmentation index can be explained in part by the short height of these patients.

[Environment and asthma in children: controversies]. / Environnement et asthme de l'enfant: controverses et jusqu' où aller?

The increase in asthma prevalence over the past 20 years could be due to modification of exposure to environmental factors (environmental theory) or to the lost of protective factors (hygienist theory). Among environmental factors this paper reviewed the controversial role of exposure to house dust mite (HDM). If exposure to HDM is deleterious in asthmatics known to be sensitised to this allergen, the effect of HDM exposure on asthma incidence has been challenged recently, based on longitudinal studies showing no correlation between level of exposure to HDM and asthma incidence. Exposure to animal dander may have protective effects. This review has shown that, even if some studies have shown potential protective effect of early exposure, the protection seems to be better in families with a low risk of atopy; almost all studies tend to show a deleterious effect of current exposure; exposure to dog dander may be more protective than cat. These studies cannot give definite conclusions to change current advices of early eviction of HDM and animal dander, especially in families with a high risk of atopy. The deleterious effect of passive smoking on asthma prevalence and severity is undisputable and our efforts should concentrate on obtaining effective eviction of passive smoking.

[Acute organophosphate intoxication after using a anti-lice insecticide shampoo]. / Intoxication aiguë par organophosphorés à la suite de l'utilisation d'un insecticide comme shampooing anti-poux.

CASE REPORT: Two children were admitted for poisoning by organophosphate pesticides applied as hair rinses against lice. These chemical agents inhibit the acetylcholinesterase enzyme at various sites. The resultant accumulation of the transmitter acetylcholine causes abnormal signs and symptoms. The diagnosis is based on a reduction in the blood cholinesterase activity. The specific treatment comprises the administration of atropine and pralidoxime. CONCLUSION: Accidental poisoning by organophosphate insecticides may occur, due to the misuse of such substances as shampoo against lice. An accurate information for users is necessary.

[Differential diagnosis of asthma in infants and young children]. / Diagnostic différentiel de l'asthme du nourrisson et du jeune enfant.

Although when an infant or a young child presents with persistent or recurrent wheezing, the probability of asthma is high, one must remain very careful in order not to miss an other etiology. Except for the chest X ray with inspiratory and expiratory studies that is mandatory, the other evaluations should be based on a careful interview and clinical examination. Fiberoptic bronchoscopy may be indicated each time there is a doubt on foreign body aspiration or tracheobronchomalacia.

[Prevention of respiratory syncytial virus infection by SYNAGIS (palivizumab)]. / Prévention de l'infection à virus respiratoire syncytial (VRS) par le SYNAGIS (palivizumab).

Infection with respiratory syncytial virus is frequent but most often benign. The serious forms of the illness, which make necessary hospitalisation or care in an intensive Care Unit, appear in infants of less than 6 weeks and especially in those with underlying pathologies, prematurity, congenital cardiopathies or chronic respiratory illnesses. Palivizumab (SYNAGIS) is mouse humanized monoclonal antibody which is used for prevention by monthly injections before and during the epidemic period. In a pivotal study performed on 1502 infants aged less than 6 months and former prematures of less than 36 weeks gestational age (GA) or aged less than 2 years and preventing a bronchopulmonary dysplasia, 1002 infants received 5 monthly injections, compared with 500 infants treated with placebo. There was a significant reduction of 55% risk of hospitalisation with VRS infections in the treated group, but no significant reduction in the number of stays in intensive care or deaths. The recommendation in France now is to use SYNAGIS in children aged less than 6 months, born with or GA of less then 32 weeks or aged less than 2 years and presenting a bronchopulmonary dysplasia. Questions remain on the cost-benefit ratio of this treatment and the favourable effects of this treatment in children who carry other chronic pulmonary or cardiac pathologies.

Acromicric dysplasia: long term outcome and evidence of autosomal dominant inheritance.

Acromicric dysplasia is a rare bone dysplasia characterised by short stature, short hands and feet, normal intelligence, mild facial dysmorphism, and characteristic x ray abnormalities of the hands. Only a very small number of children with this condition have been reported so far. Here we report on a series of 22 patients including 10 boys and 12 girls with acromicric dysplasia. Length was normal at birth and height fell progressively off the centiles postnatally. The mean adult height was 130 cm (133 cm in males, 129 cm in females). The hands, feet, and limbs were short and OFC was normal. Intelligence was normal and mild dysmorphic features were noted. Other occasional features included well developed muscles, a hoarse voice, generalised joint limitation in some patients, frequent ear, tracheal, and respiratory complication, and spine abnormalities. Long term follow up showed that facial dysmorphism was less obvious in adults and that carpal tunnel syndrome was frequent in older patients. Apart from short metacarpals and phalanges, internal notch of the second metacarpal, external notch of the fifth metacarpal, and internal notch of the femoral heads, there were no major x ray abnormalities. No major complications, such as cardiac disease or major orthopaedic problems, occurred in the course of the disease. The condition appeared to be sporadic in 16 cases but the observation of vertical transmission in three families was consistent with an autosomal dominant mode of inheritance.