Headache as the sole manifestation of Wilson’s disease

Wilson’s disease (WD) is an inborn error of copper metabolism caused by a mutation to the copper-transporting gene ATP7B. In the first decade of life, hepatic involvement predominates but neurological manifestations occur in the third or fourth decades. Studies showed Indian children with neuro WD present with behavior abnormality, speech and cognitive impairment, sub-clinical affection of visual pathway, and autonomic function. As a treatable disease, WD should be detected early in the course of the disease by any health professional at any care level, but the rare prevalence of the disease explains the lack of awareness of this disease. Even a high index of suspicion about this entity gets more difficult when the rare and atypical symptom is the only presentation of the disease. Here, we present the case of a 15-year-old girl with worsening headache for the past 3 months as the only neurological manifestation of WD, and that also without any evidence of hepatic involvement.

Research Progress of Therapeutic Mechanism of Gandou Decoction in Treatment of Wilson's Disease / 中国实验方剂学杂志

Wilson disease (WD) is a treatable neurological inherited disorder characterized by copper metabolism impairment. Metal chelating drugs, such as penicillamine, have been used to treat WD for decades, is exposuring its limitations of effect and utilize sphere. Genetic therapy was considered as the most potential way of curing WD, is still can only be achieved in the laboratory, which have massive problems to solve before its clinical utilization. Based on this, we started to research the curative mechanism of traditional Chinese medicine(TCM) donated by national natural science fund project funding, found that TCM formula Gandou decoction regulate the metabolic disorders caused by liver cells and neurons apoptosis, autophagy, such as programmed cell death,from the molecular pathways of copper metabolism, Wnt/β-catenin pathway and mitogen-activated protein kmase(MAPK) pathways regulating liver damage such as cell signaling pathways, extracellular signal-regulated kinase(ERK) pathway and liver kinase B1(LKB1)/adenosine monophosphate activated protein kinase(AMPK) pathway and the cell signaling pathway of neuronal damage. The above experimental results were verified by TX mice, a reliable WD animal models. This paper aimed to systematically review the research of GDD therapeutic mechanisms from the sight of programmed cell death, including aptosis and autophagy, and provided theoretical for formula optimization. In addition, we elaborated some assumptions and feasible advice for the further research of GDD therapeutic mechanism.

Clinical characteristics of patients with delayed hepatolenticular degeneration / 中华内科杂志

Objective To evaluate the clinical manifestations, metal metabolism, imaging characteristics and treatment response in patients with delayed Wilson disease (WD). Methods Patients with untreated WD (40 with delayed onset and 40 with non?delayed onset) were enrolled. Twenty healthy people were included as normal controls. All patients were evaluated with modified Young scale neural symptom scores, grade of Child liver function and mental symptoms rating scale, magnetic resonance imaging (MRI) scan, magnetic sensitive imaging (susceptibility weighted imaging, SWI), metal metabolism. Corrected phase (CP) was measured at SWI. After 2 week treatment, neurologic symptoms, liver function, and metal metabolism were reviewed. Results The total score of neurological symptoms in WD patients with delayed onset was lower than that of non?delayed onset (13.00 ± 6.87 vs. 21.13 ± 5.53, P=0.033). The scores of SCL?90 and HAMA depression scales in patients with delayed onset were lower than those of non?delayed onset. On T2 weighted imaging, areas including substantia nigra and thalamus, the caudate nucleus, globus pallidus, putamen presented high signal rate in patients with delated onset than those with non?delayed (P=0.022, 0.037, 0.022, 0.037, 0.029 respectively). The SWI CP values of cangbai sphere and shell nucleus in patients with delayed onset were lower than those with non?delayed onset. Patients with delayed onset had higher urinary copper than those with non?delayed onset before and after treatment (P=0.040, 0.036). After treatment, the score of abnormal tremor and gait in patients with delayed onset was decreased (P=0.037, 0.044), while as the occurrence of neurological symptoms was increased by 10%, and the liver function level in patients with delayed WD was decreased in 3 cases. Conclusions The brain of WD patients with delayed onset is mainly composed of metal deposits, however the cell damage is not apparent. Clinical symptoms are characterized by significant liver injury, but relatively mild neurological and psychiatric symptoms. Patients with delayed WD have higher urinary copper excretion than those with non?delayed WD. Chelating agents improves the neurological symptoms in patients with delayed onset.

Research progress in Menkes disease / 国际儿科学杂志

Menkes Disease (MD) is a multisystemic disorder of impaired copper metabolism with an X-linked recessive inheritance,which is caused by defects in ATP7A gene encoding a copper-transporting AT-Pase.It is characterized by infantile onset,peculiar curls and facial changes,mental retardation with progressive neurodegeneration,as well as hypotonia and connective tissue abnormalities.Many intermediate phenotypes have been found in recent years,the mildest form of which is occipital horn syndrome (OHS).Its clinical variants show a broad spectrum from chromosome abnormalities to single-nucleotide mutation.Early copper-histidine supplementation is still the most crucial treatment at present,and L-DOPS combination therapy may benefit some patients clinically.This article reviews the pathogenesis,clinical features and the progress of diagnosis and treatment of MD.

Wilson's Disease: a case report and a historical review / Doença de Wilson: relato de caso e revisão histórica

The purpose of this report is to present a short review of the history of Wilson’s disease and to describe the first diagnosed case at the Neurologic Clinic of Hospital das Clínicas of São Paulo University Medical School. The topics of the historical review are the first contributions of authors along the second half of the XIX century, the seminal monograph of Samuel Alexander Kinnier Wilson (1912), the landmarks in the investigation of mechanisms of the disease and the introduction of the first effective treatment by John Walshe (1956). The first case studied in our Clinic, in 1946, was a 20 year-old male whose main neurological manifestations were postural tremor (“wing beat”) and dysarthria and could be characterized as Westphal-Strümpell form of the disease. Along the discussion of this case difficulties to establish the diagnosis and to treat the patient at that time are highlighted. We conclude with a brief history of the development of researches on Wilson’s disease in our Clinic, with an honor to the pioneer contributions of Horácio Martins Canelas.

Neste artigo inicialmente é feito um retrospecto dos principais marcos na história dos conhecimentos sobre a doença de Wilson, desde as primeiras descrições de casos no século XIX, passando pela magnífica monografia de Samuel Alexander Kinnier Wilson, m 1912, pelas descobertas sobre a causa da doença e chegando à era do tratamento efetivo da moléstia inaugurada por Walshe em 1956. A seguir, relata-se o primeiro caso de doença de Wilson estudado na Clínica Neurológica do HC-FMUSP. O paciente admitido na Clínica Neurológica em 1946, aos 20 anos de idade, apresentava a variante da doença em que predominavam tremor postural e disartria, conhecida como forma de Westphal-Strümpell. Na discussão, são ressaltadas as dificuldades da época para a confirmação do diagnóstico e para o tratamento; além de se realizar um breve histórico do estudo da doença na Clínica Neurológica, com o devido realce para a figura de Horácio Martins Canelas, pela sua participação pioneira nas pesquisas sobre a doença de Wilson em nosso meio.

A Study on the Relations among Zinc Copper Metabolism, Blood Glucose, Insulin and Serum Lipids in Normal Adult Women / 대한지역사회영양학회지

The purpose of this study was to investigate zinc and copper metabolism and risk factors of chronic diseases in 20 normal adults women. The daily intake, excretions in urine and feces, and serum levels of zinc and copper were determined by 24-hr food records and chemical analysis. The results were summarized as follows. mean age, body weight and BMI were 22.88 years, 54.65 kg and 21.28 kg/m2 respectively. Mean daily intakes of energy and protein were 1578.84 kcal(79% of RDA) and 52.05g (87% of RDA). The zinc and copper intake, excrestion in urine and feces were 7093.23 microgram(59% of RDA/2093.87 microgram, 203.50 microgram/39.87 microgram and 3416.41 microgram/857.62 microgram, respectively. The serum levels of fasting glucose, insulin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride, zinc and copper were 76.60 mg/dl, 15.66IU/dl, 160.30 mg/dl, 50.95 mg/dl, 89.80 mg/dl, 89.79 mg/dl, 95.65 microgram/dl and 73.28 microgram/dl respectively. Dietary ratio of Zn to Cu was shown to have significant positive correlations with serum insulin, total cholesterol, LDL-cholesterol. The urinary ratio of Zn to Cu was shown to have significant positive correlations with triglyceride. The serum copper level was shown to have significant negative correlations with serum total cholesterol and LDL-cholesterol. In summary, Zn consumption of adult women in their normal diet does not meet the Zn requirement for Koreans. Also, intakes of Zn and Cu may effect the glucose metabolism and cardiovascular diseases. Therefore, to increase the Zn intake and to maintain an appropriate intake ratio of Zn to Cu, nutrition education needs to be implemented.

The Effect of Common Bile Duct Ligation on Liver Morphology and Coper Metabolism in Rat

To clarity the effect of biliary obliteration on copper metabolism of rat liver and on the hepatic morphology, 0.5% cuppuric sulfate was administered intraperitoneally for 42 days following ligation of the common bile duct (CBD) of Sprague-Dawley rats. The blood copper concentration, the hepatic copper content and the accumulation patterns of copper and copper binding protein in the liver were examined and compared with those of the simple CBD ligation group and the simple copper over loaded group. CBD ligation induced marked proliferation of bile ductular structures which, after expanding the portal tracts, invaded and divided the hepatic lobules. There was, however, no excess fibosis beyond what needed to support the new ductules. The blood copper concentration and the hepatic copper content were increased by copper overload with or without CBD ligation, particularly incases with CBD ligation. Liver cell necrosis did not occur by the overloaded copper alone in rats. The hepatic copper and copper binding protein were accumulated at periportal liver cells in the group of coppe overload after CBD ligatio, whereas they began to appear at perivenular hepatocytes in the simple copper overloaded group. In conclusion, it is suggested that CBD ligation does not induce excess fibrosis or liver cirrhosis in rat as far as during our experimental period, but affect significantly on copper metabolism by intrahepatic redistribution of the copper and the copper binding proteins.