Hereditary spastic paraplegia (SPG 48) with deafness and azoospermia: A case report.

Hereditary spastic paraplegias (HSP) are inherited neurodegenerative disorders characterized by progressive paraplegia and spasticity in the lower limbs. SPG48 represents a rare genotype characterized by mutations in AP5Z1, a gene playing a role in intracellular membrane trafficking. This study describes a case of a 53-year-old male patient with SPG48 presenting spastic paraplegia, infertility, hearing impairment, cognitive abnormalities and peripheral neuropathy. The Sanger sequencing revealed a homozygous deletion in the chr 7:4785904-4786677 region causing a premature stop codon in exon 10. The patient's brother was heterozygous for the mutation. The brain magnetic resonance imaging found a mild brain atrophy and white matter lesions. In the analysis of the auditory thresholds, we found a significant hearing decrease in both ears.

Persistence with medical treatment for Wilson disease in China based on a single center's survey research.

BACKGROUND: Wilson's disease (WD) is one of the few hereditary diseases that can be successfully treated with medicines. We conduct this survey research to assess treatment persistence among patients with WD and try to identify what factors affect the treatment persistence. METHODS: We employed WeChat which is the most popular social software in China to carry out this anonymous questionnaire research. The questionnaire included medication adherence scale. We also collected available medical records related to demographic and clinical characteristics. All the patients were divided into group of persistence with drug treatment (PDT) and nonpersistence with drug treatment (n-PDT). RESULTS: We collected 242 qualified questionnaires. Only 66.5% of patients were PDT during the mean 12.6 years of follow-up. In PDT group, better outcomes were observed: improvement (78.3%) and no change (16.1%) versus those in n-PDT (55.6%; and 28.4%, respectively). In PDT group, only nine patients deteriorated (6.8%) in comparison with 13 patients in n-PDT (16.0%). The adverse events (AEs) in PDT group were significantly less than those in n-PDT group. There were no significant differences in clinical type, gender, age, education level, and family knowledge about WD between the two groups. There were significant differences in AEs and family position toward treatment. CONCLUSION: Medication Adherence of Chinese WD patients was low. One third of the patients (33.5%) were unable to PDT, and it had an important negative effect on clinical outcome. AEs and family support had an important impact on treatment persistence.

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.

[Study on correlation between neuropsychological features and Chinese medical syndrome types in patients with Wilson's disease].

OBJECTIVE: To explore the correlation between neuropsychological features and Chinese medical syndrome types in Wilson's disease (WD) patients, thus providing evidence for early intervention by syndrome typing. METHODS: Totally 96 WD patients were assigned to Gan-Dan damp-heat syndrome (GDDHS, 31 cases), Gan-Shen yin deficiency syndrome (GSYDS, 47 cases), and qi-blood deficiency syndrome (QBDS, 18 cases) by syndrome typing. Three items of neuropsychological testing were performed in them, i.e., Raven's standard progressive matrices (R'SPM), Stroop color-word test (CWT), trail making test (TMT). The correlations between the integrals of Chinese medical syndrome types and results of the 3 tests were analyzed. RESULTS: (1) There was statistical difference in the total scores of R'SPM, the word interference time of CWT, and interference effects of TMT among the 3 syndrome types (P <0.01, P <0.05). There was statistical difference in the total scores of R'SPM and the word interference time of CWT in patients of QBDS, when compared with those of GDDHS and GSYDS (P <0.05). There was statistical difference in interference effects of TMT in patients of GDDHS, when compared with those of QBDS and GSYDS (P <0.05). (2) The integrals of the 3 syndrome types were negatively correlated with the total scores of R'SPM (P <0.01). The integral of GDDHS was significantly positively correlated with the interference effects of TMT (P <0.01). The integral of GSYDS was significantly positively correlated with TMT-B time consumption and interference effects of TMT (P <0. 05). The integral of QBDS was significantly positively correlated with the word interference time of CWT (P <0.05). CONCLUSIONS: There was correlation between neuropsychological changes of WD patients and Chinese medical syndrome types. The severity of asthenia syndrome was sequenced from high to low as QBDS > GSYDS > GDDHS. The severity of asthenia was higher than that of asthenia.

[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.

[Clinical study on manifestation of hepatolenticular degeneration complicated with epilepsy and therapeutic effect of integrative Chinese and Western medicine treatment].

OBJECTIVE: To observe the clinical manifestation of 155 patients with hepatolenticular degeneration (HLD) complicated with epilepsy and the therapeutic effect of integrative Chinese and Western medicine treatment on them. METHODS: Clinical manifestation of patients and its relationship with abnormalities in cranial CT and/or MRI were observed. Patients were treated by combined treatment of copper repellent with sodium dimercaptosulfonate 20 mg/kg per day by intravenous dripping, and modified Gandou Decoction (GDD) by oral intake and antiepileptics as well, after treatment for 8-10 courses, the clinical effect, copper levels in urine and serum were compared between groups. RESULTS: In the 155 HLD patients, 96 were complicated with petit mal and 59 with grand mal. In the CT and/or MRI conducted in 72 patients, all showed abnormal images, besides such frequently met images as bilateral symmetrical basal ganglia focal lesion in 65 case-episode (90.3%) and brain atrophy of various degrees in 61 case-episode (84.7%), the massive lesions in cerebral white matter as principal, with the cortex involved, were also found in 54 patients (74%), which were mostly bilateral and symmetric or located in 2 adjecent lobes of brain, the sites of damage, in sequence of occurrence, were frontal lobe, parietal lobe, temporal lobe and callosal gyrus. Brain atrophy was found in all the remained patients without above-mentioned lesions. Abnormal EEG was shown in 29 patients (40.2%), which mainly manifested as theta wave of moderate to high potential and/or short paroxysmal spike-slow or sharp-slow complex wave evoked. The urinary copper level in patients after treatment was 34.5 +/- 21.6 micromol/24 hrs, significantly higher than that before treatment, 4.49 +/- 1.93 micromol/24 hrs (P < 0.01). And the serum copper level in patients also lowered significantly (P< 0.01). Epileptic seizure was controlled completely along with the gradually improving of extrapyramidal symptoms. CONCLUSION: Partial seizure was the most common type of seizure of HLD patient complicated with epilepsy, the next is systemic seizure. Cerebral damage lesion and obvious brain atrophy could be the main etiological factors of HLD complicated with epilepsy, combined copper repellent therapy of integrative Chinese and Western medicine, and antiepileptics produced good clinical effect on the patients.

Copper-chelating therapeutic effect in Wilson disease with different clinical phenotypes and polymorphisms of ATP7B gene.

AIM:To investigate the copper-chelating therapeutic effect in Wilson disease (WD) with different clinical phenotypes and polymorphisms of ATP7B gene.METHODS:One hundred and twenty-two WD patients with different clinicalphenotypes were given DMPS intravenously and Gandou copper-chelating tablet orally for one month. The therapeutic effect was judged by modified Goldstein mothod. Exon 18 of ATP7B gene extracted from the DNA of patients and 20 healthy volunteers was amplified with PCR mutation and polymorphism were screened with SSCP technique.RESULTS:Four kinds of abnormal migration bands in PCR-SSCP were observed in 37 WD patients, mutation frequencies of three different disease phenotypes, and curative effect between mutation group and non-mutation group showed no statistically significant difference (P > 0.05), but the total effectiveness rates in patients with Wilson type or pseudosclerosis type were significantly higher than those of patients with hepatic type (X(2) = 6.17, P < 0.05).CONCLUSION:Most WD patients are compound heterozygotes, the patients with different clinical phenotypes have different response to copper-chelating therapy. Specific mutation, at least in part, plays a role in influencing the disease phenotypes and therapeutic effect.