Sexual dysfunction in Wilson disease: Prevalence and influencing factors.

Wilson disease is a rare neurogenetic disorder that receives significant attention due to its manifestations, such as jaundice, cirrhosis, tremor, dystonia, and others. However, the impact of Wilson disease on sexual function has been overlooked. In this study, we aimed to investigate current status of sexual dysfunction in Wilson disease. In this study, we investigated the sexual function status and possible influencing factors of 245 Wilson disease patients by questionnaire. Our study identified sexual dysfunction as a prevalent issue in Wilson disease patients, with an overall prevalence of 49.0 %, of which 33.9 % in males and 63.7 % in females, both higher than the prevalence of sexual dysfunction in the normal Chinese population. Compared with non-sexual dysfunction patients, sexual dysfunction was more common in the older age group, females, less educated, rural residence, no occupation, lower income, taking sedatives/antipsychotics, and high SIS scores (P < 0.05). Our binary logistic regression analysis revealed that older age (OR: 1.103, 95 %CI: 1.058-1.151, P < 0.001), being female (OR: 5.900,95 %CI: 2.966-11.736, P < 0.001), and the use of antipsychotics or sedatives (OR: 3.277,95 %CI: 1.065-10.077, P < 0.05) were all positively linked with an increased risk of sexual dysfunction. Despite the well-known symptoms of Wilson disease, sexual dysfunction is also a frequent issue in Wilson disease patients, necessitating further attention.

Case report: A Chinese patient with spinocerebellar ataxia finally confirmed as Gerstmann-Sträussler-Scheinker syndrome with P102L mutation.

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare genetic prion disease caused by a mutation in the prion protein (PRNP) gene. It is typically characterized by progressive cerebellar ataxia and slowly progressive dementia. We present a case study of the GSS from China in which a 45-year-old male with a progressive gait and balance disorder developed cerebellar ataxia onset but was misdiagnosed as spinocerebellar ataxia (SCA) for 2 years. The patient's clinical, electrophysiological, and radiological data were retrospectively analyzed. Examination revealed ataxia, dysarthria, muscle weakness, areflexia in lower limbs, including a pyramidal sign, whereas cognitive decline was insignificant. His late mother had a similar unsteady gait. An electroencephalogram (EEG) showed normal findings, and 14-3-3 protein was negative. A brain MRI was performed for global brain atrophy and ventricular enlargement. Positron emission tomography-computed tomography (PET-CT) (18F-fluoro-2-deoxy-d-glucose, FDG) images showed mild to moderate decreased glucose metabolism in the left superior parietal lobe and left middle temporal lobe. According to genetic testing, his younger brother also had the P102L variant in the PRNP gene. This single case adds to the clinical and genetic phenotypes of GSS.

A weighted cranial diffusion-weighted imaging scale for Wilson's disease.

Objectives: Cranial magnetic resonance imaging (MRI) could be a crucial tool for the assessment for neurological symptoms in patients with Wilson's disease (WD). Diffusion-weighted imaging (DWI) hyperintensity reflects the acute brain injuries, which mainly occur in specific brain regions. Therefore, this study aimed to develop a weighted cranial DWI scale for patients with WD, with special focus on specific brain regions. Materials and methods: In total, 123 patients with WD were enrolled, 118 of whom underwent 1.5 T-MRI on admission. The imaging score was calculated as described previously and depended on the following sequences: one point was acquired when abnormal intensity occurred in the T1, T2, and fluid-attenuation inversion recovery sequences, and two points were acquired when DWI hyperintensity were found. Consensus weighting was conducted based on the symptoms and response to treatment. Results: Intra-rater agreement were good (r = 0.855 [0.798-0.897], p < 0.0001). DWI hyperintensity in the putamen was a high-risk factor for deterioration during de-copper therapy (OR = 8.656, p < 0.05). The high-risk factors for readmission for intravenous de-copper therapies were DWI hyperintensity in the midbrain (OR = 3.818, p < 0.05) and the corpus callosum (OR = 2.654, p < 0.05). Both scoring systems had positive correlation with UWDRS scale (original semi-quantitative scoring system, r = 0.35, p < 0.001; consensus semi-quantitative scoring system, r = 0.351, p < 0.001.). Compared to the original scoring system, the consensus scoring system had higher correlations with the occurrence of deterioration (OR = 1.052, 95%CI [1.003, 1.0103], p < 0.05) and readmission for intravenous de-copper therapy (OR = 1.043, 95%CI [1.001, 1.086], p < 0.05). Conclusion: The predictive performance of the consensus semi-quantitative scoring system for cranial MRI was improved to guide medication, healthcare management, and prognosis prediction in patients with WD. For every point increase in the neuroimaging score, the risk of exacerbations during treatment increased by 5.2%, and the risk of readmission to the hospital within 6 months increased by 4.3%.

The study of Wilson disease in pregnancy management.

INTRODUCTION: Pregnancy management in women with Wilson disease (WD) remains an important clinical problem. This research was conducted to investigate how to avoid worsening of WD symptoms during pregnancy and increase pregnancy success in women with WD by identifying the best pregnancy management approaches in these patients. PATIENTS AND METHODS: The clinical data of 117 pregnancies among 75 women with WD were retrospectively analyzed. Related information of the fetus was also recorded and analyzed. At the same time, regression analysis was performed for data of 22 pregnant women without WD, as normal controls. RESULTS: Of a total of 117 pregnancies among the 75 women with WD and 31 pregnancies among the 22 control womenincluded in this study, there were 108 successful pregnancies and 9 spontaneous abortions. Among the 108 successful pregnancies, 97 women a history of copper chelation therapy before pregnancy; all 97 women stopped anti-copper therapy during pregnancy. The nine women with spontaneous abortion had no pre-pregnancy history of copper displacement therapy. The incidence of lower limb edema was higher in the WD group than in normal controls (P = 0.036). Compared with the control group, there was a higher proportion in the WD group of male infants (P = 0.022) and lower average infant birth weight (t = 3.514, P = 0.001). CONCLUSION: It is relatively safe for women with WD patients to become pregnant. The best management method for pregnancy in women with WD may be intensive pre-pregnancy copper chelation therapy and no anti-copper treatment during pregnancy.

Characteristics of neurological Wilson's disease with corpus callosum abnormalities.

BACKGROUND: Wilson's disease (WD) is an autosomal recessive disease of impaired copper metabolism. Previous study demonstrated that WD with corpus callosum abnormalities (WD-CCA) was limited to the posterior part (splenium). This study aimed to compare clinical features between WD-CCA and WD without corpus callosum abnormalities (WD-no-CCA). METHODS: Forty-one WD patients who had markedly neurological dysfunctions were included in this study. We retrospectively reviewed clinical, biochemical characteristics and MRI findings in the 41 WD patients. All patients were assessed using the Unified Wilson's Disease Rating Scale. RESULTS: Nine patients had corpus callosum abnormalities, 4 of 9 patients had abnormal signal in the genu and splenium, 5 of 9 patients had abnormal signal only in the splenium. WD-CCA had longer course (9.9 ± 4.0 years vs. 3.4 ± 3.6 years, p<0.01), more severe neurological dysfunctions (37.6 vs. 65.9, p<0.01) and higher psychiatric symptoms scores (11.2 vs. 22.5, p<0.01) than WD-no-CCA. The MRI findings indicated that WD-CCA had higher ratio than WD-no-CCA in globus pallidus (88.9% vs. 43.8%, p = 0.024) and thalamus (100% vs. 59.4%, p = 0.038). The index of liver function and copper metabolism had no significant in WD-CCA and WD-no-CCA patients. CONCLUSION: Our findings indicate Wilson's disease can involve the posterior as well as the anterior part of CC and patients with CC involvement had more extensive brain lesions, more severe neurological dysfunctions and psychiatric symptoms.

A case report: Co-occurrence of Wilson disease and oculocutaneous albinism in a Chinese patient.

RATIONALE: Both Wilson disease (WD) and Oculocutaneous Albinism (OCA) are rare autosomal recessive disorders that are caused by mutations on chromosome 13 and chromosome 11, respectively. Here, we report on a patient with coexisting WD and OCA, initially presenting episodes of tremors. PATIENT CONCERNS: WD is a disorder of copper metabolism. The main sites of copper accumulation are the liver and the brain, resulting in hepatic symptoms. OCA is a disorder of melanin biosynthesis, characterized by a generalized reduction in pigmentation of the eyes (oculo-), skin (-cutaneous), and hair. DIAGNOSIS: The diagnosis of WD was confirmed by neurological symptoms, metabolism tests, and MRI scans. Interestingly, the patient also had very light skin color, blond hair and eyebrows, and dark brown eyelashes and irises. Because the association of dermatologic signs in WD has rarely been reported, OCA was highly suspected based on these clinical findings. Genetic analysis was subsequently conducted, and the results revealed the p. (Arg778Leu) mutation in 1 allele and the p. (Asn1270Ser) mutation in the other allele of the ATP7B gene, confirming the diagnosis of WD; the p. (D456fs) mutation in 1 allele and the p. (R299H) mutation in the other allele of the TYR gene, confirming the diagnosis of OCA. The family history was positive for WD with a 14-year-old younger brother also being diagnosed with it. Her parents are negative for OCA and WD. INTERVENTIONS: Sodium dimercaptopropanesulfonate (DMPS) was given during hospitalization. D-penicillamine and zinc sulfate treatment was initiated after discharge for long-term control. OUTCOMES: Postural and intention tremor disappeared, and other symptoms and signs markedly improved after treatment. LESSONS: In this study, we reported on the first case of a child who simultaneously presented WD and OCA, bringing up the possibility of a presumable link between these 2 rare diseases.

Long-term outcomes of a patient with late-onset multiple acyl-CoA dehydrogenase deficiency caused by novel mutations in ETFDH: A case report.

RATIONALE: Late-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD) mainly affects the neck extensor muscle group, which has been confirmed by novel mutations in electron-transferring-flavoprotein dehydrogenase (ETFDH). So far, a few cases have been reported with long-term follow-up. Here we report a case of late-onset MADD where the patient was followed up for 8 years during which time he underwent 2 muscle biopsies and 2 pathological examinations and his symptoms were significantly alleviated after appropriate treatments. PATIENT CONCERNS: In September 2009, a 16-year-old male patient was hospitalized due to gradually increasing difficulty in raising his head and weakness in limb muscles over a 6-month period. During the physical examination, the patient's neck extensor muscle strength was grade III-IV. His proximal limb muscle strength was grade IV, and his distal muscle strength was normal. His blood creatine kinase (CK) was 783 U/L. DIAGNOSIS: Muscle biopsy revealed a large number of vacuolar fibers, which were mainly type I fibers. These findings were consistent with the diagnosis of lipid storage myopathy (LSM). ETFDH gene test detected C.736G > A at exon 7 and C.920C > G at exon 8. INTERVENTIONS: Coenzyme Q10 treatment was administered. The first coenzyme Q10 40 mg tid was treated for three months, with the change of coenzyme Q10 20 mg tid for 6 months, followed by the change of coenzyme Q10 10 mg tid for long-term use. OUTCOMES: The patient's condition significantly improved after 3 months. At 7th year follow-up the patient's blood CK was normal, and a second muscle biopsy revealed no muscle vacuolar fibers and no increase in lipid droplets. Subsequently, the patient was withdrawn from the coenzyme Q10 treatment, and the condition of the patient remained normal. LESSONS: Muscle biopsy was the main method used to determine LSM. Treatment with riboflavin should be started when the diagnosis of LSM is definitive. Furthermore, ETFDH gene tests should be performed for further classification. Moreover, coenzyme Q10 may be another effective drug for MADD.

The c-Abl inhibitor in Parkinson disease.

Parkinson's disease (PD) is an insidious onset neurodegenerative disease affecting approximately 1% of the population over the age of 65. So far available therapies for PD have only aimed at improving or alleviating symptoms, but not at slowing, preventing, and reversing the course of PD. Recently, some studies have indicated that the levels and activation of Abelson non-receptor tyrosine kinase (c-Abl, Abl1) were up-regulated in the brain tissue of patients with PD and demonstrated that c-Abl inhibitors could improve motor behavior, prevent the loss of dopamine neurons, inhibit phosphorylation of Cdk5, regulate α-synuclein phosphorylation and clearance, inhibit the tyrosine phosphorylation of parkin and decrease parkin substrate, for example, PARIS (zinc finger protein 746), AIMP2 (aminoacyl-tRNA synthetase-interacting multifunctional protein type2), FBP1 (fuse-binding protein 1), and synphilin-1. Therefore, we review the mechanism of the c-Abl inhibitor in PD and conclude that c-Abl inhibitors may be a potential treatment in PD and other neurodegenerative disease.

[The Correlation between Blood Uric Acid and Goldstein Grading in Hepatolenticular Degeneration Patients with Different Chinese Medical Syndrome Types].

OBJECTIVE: To observe blood uric acid levels and Goldstein grading, as well as their correlation in Wilson's disease (WD) patients with different Chinese medical syndrome types. METHODS: Totally 906 WD patients in line with inclusive criteria were assigned to 6 groups, i.e., the heart spirit confused by phlegm group (HSCP, 26 cases), the phlegm-fire disturbing heart group (PFDH, 90 cases), the retention of damp-heat group (RDH, 113 cases), deficiency of qi and blood group (DQB, 168 cases), the deficiency of Gan-yin and Shen-yin group (DGYSY, 327 cases), the deficiency of Gan and Shen group (DGS, 182 cases) due to different Chinese medical syndrome types. Recruited were another 160 healthy subjects having similar ages and diet structures, who came for medical examinations, as the healthy control group. Venous blood was collected from the medial cubital vein of each-patient on an empty stomach in early mornings to detect blood uric acid levels. Results Blood uric acid levels were lower in each syndrome type group than in the healthy control group (146.08 +/- 67.24 micromol/L in the HSCP group; 157.08 +/- 69.77 micromol/L in the PFDH group; 162.58 +/- 97.72 micromol/L in the RDH group; 156.20 +/- 62.63 micromol/L in the DQB group; 161.83 +/- 111.23 micromol/L in the DGYSY group; 194.41 +/- 90.01 micromol/L in the DGS group; 242.39 +/- 87.55 micromol/L in the healthy control group, P < 0.01). Blood uric acid levels were higher in the DGYSY group than in the other 5 syndrome groups (P < 0.01). Correlation analyses between Goldstein grading and blood uric acid showed that, along with increased Goldstein grade (that was aggravating disease conditions), WD patients' blood uric acid levels decreased (P < 0.01). CONCLUSIONS: WD patient's blood uric acid levels decreased more. Blood uric acid levels and Goldstein grading were different in various Chinese medical syndrome types. Blood uric acid levels had certain value in assessing the severity of WD.

[Protective effect of electroacupuncture intervention on neurovascular unit in rats with focal cerebral ischemia-reperfusion injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on behavior changes, expression of cerebral vascular endothelial growth factor (VEGF), nerve growth associated protein-43 (GAP-43), synaptophysin (SYN), myelin basic protein (MBP), neurite outgrowth inhibitor-A (Nogo-A) in cerebral focal ischemia-reperfusion injury (CI/RI) rats, so as to study its mechanism underlying improvement of ischemic cerebral vascular disease. METHODS: Sixty male SD rats were randomly divided into sham-operation group, model group and electroacupuncture (EA) group. CI/RI model was established by occlusion of the middle cerebral artery (MCAO) and reperfusion. EA was applied to bilateral "Neiguan" (PC 6), "Sanyinjiao" (SP 6), "Shuigou" (GV 26) and "Baihui" (GV 20) for 30 min, once a day for 14 days. The neurologic deficits were evaluated by Longa 5-grade standard (the higher the score, the severer the neurologic deficit). The immunoactivity of cerebral VEGF, GAP-43, SYN, MBP (important in the process of myelination of nerves in the nervous system) and Nogo-A (inhibiting axonal regeneration) in the focal ischemic cerebral tissue was detected by immunohistochemistry. RESULTS: The Longa's score of the model group was significantly increased after MCAO in comparison with the sham-operation group (P < 0.01). In comparison with the model group, Longa's score of the EA group was evidently lower on day 14 after CI/RI (P < 0.05), suggesting an improvement of the neurological deficits after EA intervention. In comparison with the sham-operation group, the immunoactivity of cerebral VEGF, GAP-43 and Nogo-A was significantly upregulated on day 7 and 14 in the model group (P < 0.01), while that of cerebral SYN was remarkably down-regulated in the model group on day 7 and 14 after CI/RI (P < 0.05). Compared with the model group, cerebral VEGF, GAP-43, SYN and MBP expression levels were considerably upregulated on day 7 and 14 following CI/RI in the EA group (P < 0.01, P < 0.05), while that of cerebral Nogo-A was significantly decreased at the two time-points in the EA group (P < 0.01). CONCLUSION: EA intervention can effectively improve neurological function in cerebral infarction rats, which is closely related to its effects in upregulating cerebral VEGF, GAP-43, SYN and MBP expression, and down-regulating Nogo-A protein, suggesting a protective effect on neurovascular unit.

[Research on the correlation between Chinese medical syndrome types and objective indices of Wilson's disease].

OBJECTIVE: To explore the correlation between Chinese medical syndrome types of Wilson's disease (WD) and clinical materials as well as physical and chemical indices. METHODS: Totally 116 WD patients were typed by Chinese medical syndrome. The correlation between Chinese medical syndrome types and clinical materials as well as physical and chemical indices were analyzed using binary stepwise Logistic regression by SPSS 19.0 Software, taking the common Chinese medical syndrome types as the dependent variable and clinical materials as well as physical and chemical indices as the independent variables. RESULTS: Gan-Galibladder dampness-heat syndrome (GGDHS, 35.3%). Gan-stagnation and Pi-deficiency syndrome (GSPDS, 13.8%), Gan-Shen yin deficiency syndrome (GSYDS, 13.8%), and phlegm-dampness retention syndrome (PDRS, 12.1%) were most often seen. GGDHS was positively correlated with grade of K-F ring, total bilirubin (TBIL), alanine transaminase (ALT), laminin (LN) (P < 0.01). GSYDS was positively correlated with TBIL (P < 0.01). PDRS was positively correlated with clinical types, ceruloplasmin (CP), aspartate aminotransferase (AST), and total protein (TP) (P < 0.01, P < 0.05). Qi blood deficiency syndrome was positively correlated with disease course, blood ammonia, blood urea nitrogen (BUN), and LN (P < 0.01, P < 0.05). CONCLUSIONS: Chinese medical syndrome types were correlated with clinical materials, physical and chemical indices in WD patients, which could provide experimental reference for Chinese medical syndrome typing. GGDHS, GSPDS, GSYDS, and PDRS were most often seen.

Multiple pharmacological actions of Yiqi Huatan Decoction in a model of depression in rats.

OBJECTIVE: To investigate the influence of Yiqi Huatan Decoction (, YHD) on a model of depression in rats under different pathological conditions. METHODS: Thirty-two male SD rats were randomly divided into 4 groups of 8: normal, model, YHD, and maprotiline. The model group, YHD group and maprotiline group used separate feeding and rats were exposed to chronic and unpredictable stress to build the depression model. From day 2, the YHD group and maprotiline group were respectively given YHD (7 g/kg) and maprotiline (10 mg/kg) by gastrogavage once daily. The normal and model groups were given the same volume of drinking water. The medication duration were 21 days. At the end of the experiment, the serum levels of copper and zinc were determined by atomic absorption spectroscopy, plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol (COR) were detected by radioimmunoassay, and levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in the hypothalamus were analysed by high performance liquid chromatography-eletricochemistry. RESULTS: Compared with the content of copper and zinc in the serum of rats in the normal group, serum copper levels in model rats were significantly increased and zinc content was significantly reduced (both P<0.05). Plasma concentrations of ACTH and COR in the model group were significantly increased compared with those in the normal group (P<0.05, P<0.01). The contents of NE, DA, and 5-HT in the hypothalamus of rats in the model group were significantly reduced compared with those of the normal group (P<0.05 or P<0.01). Compared with those in the model group, the serum copper content and plasma concentrations of ACTH and COR were significantly decreased (all P<0.05); meanwhile, serum zinc content and hypothalamic contents of NE, DA, and 5-HT were significantly increased in rats of the YHD group (all P<0.05). The same effects were also shown in the maprotiline group except for 5-HT (all P<0.05) CONCLUSION: The pharmacological actions of YHD for depression might be related to improving trace-element anomalies, reversing endocrine dysfunction, and modulating the disorders of monoaminergic neurotransmitters.

[Wilson's disease in decision-making functions of Iowa gambling task].

OBJECTIVE: To explore the presence of impaired decision-making functions of Wilson's disease patients in Iowa gambling task (IGT) and its association with basal ganglia damage. METHODS: Thirty-two IGT patients with WD (WD group) and 29 healthy people (control group) were recruited from the same period. And two options of high and low rewards were selected. Before the start of experiment, a basal figure of 2000 yuan was shown on computer display and they were prompted to win more money as much as possible. The general trend was observed with or without social learning effects. RESULTS: With the increased number of cards selected, the number of favorable and unfavorable selections shifted from negative to positive and gradually rose in the control group. However, such a pattern was absent in the WD group. The WD patients in the IGT group in Trial4 and Trial5 were significantly lower than the controls (P = 0.009 and P = 0.020). CONCLUSION: The WD IGT patients have significant impairments of policy-making functions due to the damage of basal ganglia. And the effects of copper metabolism on cerebral cortex should be further studied in WD patients.

Effect of electroacupuncture on serum copper, zinc, calcium and magnesium levels in the depression rats.

OBJECTIVE: To investigate effect of electroacupuncture (EA) on serum copper, zinc, calcium and magnesium levels in the rat models of depression. METHODS: Forty healthy SD male rats were divided into a normal group, a model group, an EA group, and a maprotiline group, 10 in each with completely random. The depression models were prepared with isolated chronic unpredictable stress method in the latter three groups. EA was given at Baihui (GV 20), Yintang (EX-HN3), Fenglong (ST 40), and Taichong (LR 3) in the EA group from the second day of modeling, once every other day, 15 min each time. The maprotiline group was administered intragastrically suspension of maprotiline (10 mg/kg), once each day. After treatment for 3 weeks, serum copper and zinc levels were detected with atomic absorption method, and the serum calcium with Arsenazo III method and magnesium with MTB method. RESULTS: Compared with the normal group, the serum copper level (3.90 +/- 1.20 mmol/L) significantly increased and the serum zinc level (2.08 +/- 0.44 mmol/L) significantly decreased in the model group (P < 0.05). Compared with the model group, the serum copper level (2.62 +/- 1.03 mmol/L) significantly decreased, the serum zinc level (2.55 +/- 0.38 mmol/L) significantly increased (P < 0.05), but the serum calcium and magnesium levels did not significantly change in the EA group and the maprotiline group. CONCLUSION: EA can regulate the change of copper and zinc levels in the body induced by depression, which is possibly one of mechanisms of effectively improving depression symptoms.

[Epidemiological study of hepatolenticular degeneration at Hanshan County, Anhui Province].

OBJECTIVE: To identify the incidence and morbidity rates of hepatolenticular degeneration (HLD) at Hanshan County, Anhui Province. METHODS: According to the principles of age stratification, cluster and random sampling, a total of 112 810 subjects were screened by cornea slit-lamp examination during the period of November 2008 to October 2009. The subjects were from recruited from schools, factories, communities, institutions and villages at Hanshan County. And they belonged to the age group of 7 - 75 years. At the same time, each subject was evaluated by the clinical examination with regards to the presence of such clinical manifestations as brain, liver, kidney, skin and other organ damage. And the examinations of copper biochemistry and abdominal ultrasound were performed for those subjects with K-F rings or their clinical manifestations suspicious of HLD. In order to confirm or exclude HLD, the penicillamine challenge test (PCT) was performed if necessary. RESULTS: Seven HLD patients had a definite diagnosis of HLD. There were classical Wilson type (n = 1), pseudosclerosis type (n = 1), mental disorder type (n = 1), liver type (n = 1) and presymptomatic (n = 3). The incidence rate was 2.66/100 000 and the prevalence rate 6.21/100 000 at Hanshan County, Anhui Province. CONCLUSION: HLD is a common disease. In order to avoid a misdiagnosis and prevent an incorrect treatment, physicians should pay more attention to this curable disease and try their best to achieve early detection, early diagnosis and early treatment.