Current status of surviving patients with arginase 1 deficiency in Japan.
Ontology highlight
ABSTRACT:
SUBMITTER: Kido J
PROVIDER: S-EPMC8495172 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Lecithin cholesterol acyltransferase (LCAT) is a lipid-modification enzyme that catalyzes the transfer of the acyl chain from the second position of lecithin to the hydroxyl group of cholesterol (FC) on plasma lipoproteins to form cholesteryl acylester and lysolecithin. Familial LCAT deficiency is an intractable autosomal recessive disorder caused by inherited dysfunction of the LCAT enzyme. The disease appears in two different phenotypes depending on the position of the gene mutation: familial LCAT deficiency (FLD, OMIM 245900) that lacks esterification activity on both HDL and ApoB-containing lipoproteins, and fish-eye disease (FED, OMIM 136120) that lacks activity only on HDL. Impaired metabolism of cholesterol and phospholipids due to LCAT dysfunction results in abnormal concentrations, composition and morphology of plasma lipoproteins and further causes ectopic lipid accumulation and/or abnormal lipid composition in certain tissues/cells, and serious dysfunction and complications in certain organs. Marked reduction of plasma HDL-cholesterol (HDL-C) and corneal opacity are common clinical manifestations of FLD and FED. FLD is also accompanied by anemia, proteinuria and progressive renal failure that eventually requires hemodialysis. Replacement therapy with the LCAT enzyme should prevent progression of serious complications, particularly renal dysfunction and corneal opacity. A clinical research project aiming at gene/cell therapy is currently underway.
| S-EPMC8265425 | biostudies-literature
Project description:Arginase deficiency is a rare autosomal recessive urea cycle disorder (UCD) caused by mutations in the ARG1 gene encoding arginase that catalyses the hydrolysis of arginine to ornithine and urea. Patients have hyperargininaemia and progressive neurological impairment but generally suffer fewer metabolic decompensations compared to other UCDs. The objective is to describe the clinical features, biochemical profile, neuroradiological findings and experience of managing children with arginase deficiency. Twenty-year retrospective review of patient medical records at a single metabolic centre was performed. Six patients from three unrelated families were identified. Mean age at first symptom was 3.3 (1.5-9.0) years, while mean age at diagnosis was 8.8 (0.16-15.92) years. Four patients developed spastic diplegia and two of six with spastic quadriplegia with classical features including hyperreflexia, clonus and toe walking. This resulted in gait abnormalities that have been monitored using the GAITRite system and required Achilles tendon release in five children. Generalised tonic-clonic seizures and/or absences were present in three of six children and were controlled with anticonvulsants. All patients had moderate learning difficulties. Neuroimaging showed cerebral/cerebellar atrophy in four patients and basal ganglia abnormalities in two. Arginine levels were universally elevated throughout follow-up despite protein restriction, essential amino acid supplementation and ammonia scavengers, and neurological outcome was generally poor. Two patients died following severe metabolic decompensation in adolescence. Children with arginase deficiency continue to present a management challenge of what appears to be an inexorable course of neurocognitive impairment. Further insight into disease mechanisms may provide insight into novel treatment strategies.
| S-EPMC8898719 | biostudies-literature
Project description:This is a retrospective study aimingto clarify the current status of preimplantation genetic diagnosis (PGD) in Japan. Our data were collected from 12 facilities between September 2004 and September 2012, and entered into a database. A majority of PGD in Japan was performed for balanced structural chromosomal abnormalities in couples with recurrent miscarriage. PGD for monogenic diseases was performed only in two facilities. The average maternal age was 38 years for monogenic diseases and 40 years for chromosomal abnormalities. Overall there have been671 cycles to oocyte retrieval reported. Of these cycles, 85% (572 cycles)were for chromosomal abnormalities, and 15% (99 cycles) for monogenic diseases. Diagnosis rates in the current study were 70.8% for monogenic diseases and 94.0% for chromosomal abnormalities. Rates of embryo transfer of PGD were 62.7% for monogenic diseases and 25.5% for chromosomal abnormalities. Clinical pregnancy rates per embryo transfer were 12.0% for monogenic diseases and 35.6% for chromosomal abnormalities. Our study is the first PGD report from all facilities which had the approval of the ethics committee of the Japanese Society of Obstetrics and Gynecology. We have built a basis for gathering continuous PGD data in Japan.
| S-EPMC4464542 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) causes morbidity and mortality worldwide. Due to the improvement in environmental sanitation and medical care, the general life span has increased in the past decades in Japan. However, many older patients with COPD develop a wide range of comorbidities, and the impairments in the activities of daily living result in frailty and increase social and economic burdens. Population-based studies have shown that the prevalence of COPD is approximately 10% among subjects aged ≥40 years, but more than 80% of COPD patients are underdiagnosed. The Ministry of Health, Labour, and Welfare in Japan proposed the National Health Promotion in the 21st century, termed Health Japan 21 (the second term), in 2013 to prevent the onset and progression of noncommunicable diseases (NCDs), including COPD. The government, medical society, and community have been attempting to increase the recognition of COPD and promote smoking cessation. Additionally, Japanese cohorts have revealed distinct clinical features in Japanese patients with COPD, including lower rates of patient-reported exacerbations, less frequent coexisting cardiovascular disease and metabolic syndrome, and lower use of inhaled corticosteroids in Japan compared to the Western countries. Moreover, the poor adherence to inhaled medications is found in approximately 20% of subjects, and rehabilitation is performed in 26% of hospitalized patients with COPD. Therefore, more efforts should be made to improve adherence and access to pulmonary rehabilitation. Overall, Japanese COPD patients share common clinical and social features with COPD patients in other countries. Further international corroboration may help establish better comprehensive management of the disease.
| S-EPMC8264685 | biostudies-literature
Project description:In Japan, uterine cancer screening during pregnancy is subsidized by public funds. We examined the current status of the results of cervical cytology conducted during pregnancy in Japan. We requested 2,293 obstetrical facilities to provide information on cervical cytology in pregnant women who delivered between October 2018 and March 2019. A total of 1,292 obstetrical facilities responded, with valid information on a total of 238,743 women. The implementation rate of cervical cytology during pregnancy was 86.8% in Japan. The prevalence of abnormal cervical cytology during pregnancy was 3.3% in total and 4.9% using a spatula/brush with liquid-based cytology (LBC). The prevalence of positive high-risk human papillomavirus (HPV) in teenagers with atypical squamous cells of undetermined significance (ASC-US) was significantly higher than women of other ages (p < 0.01). Because HPV vaccine coverage has dropped to less than 1% in Japan, a further study with various conditions will be needed to improve the accuracy of cervical cancer screening during pregnancy.
| S-EPMC7790376 | biostudies-literature
Project description:BackgroundPompe disease is an autosomal recessive inherited metabolic disorder caused by a deficiency of the acid α-glucosidase (GAA). Pompe disease manifests as an accumulation of lysosomal glycogen in the skeletal and heart muscle. We conducted newborn screening (NBS) for Pompe disease in Japan from April 2013 to October 2020 to determine the feasibility and utility of NBS for Pompe disease.ResultsFrom the 296,759 newborns whose enzyme activity was measured, 107 of which underwent GAA analysis, we found one patient with infantile-onset Pompe disease (IOPD) and seven with potential late-onset Pompe disease (LOPD). We identified 34 pseudodeficient individuals and 65 carriers or potential carriers. The frequency of patients with IOPD was similar to that in the United States, but significantly lower than that in Taiwan. One patient with IOPD underwent early enzyme replacement therapy within a month after birth before presenting exacerbated manifestations, whereas those with potential LOPD showed no manifestations during the follow-up period of six years.ConclusionsThe frequency of IOPD in Japan was similar to that in the United States, where NBS for Pompe disease is recommended. This indicates that NBS for Pompe disease may also be useful in Japan. Therefore, it should be used over a wider region in Japan.
| S-EPMC8684119 | biostudies-literature
Project description:Deficiency of liver arginase (AI) causes hyperargininemia (OMIM 207800), a disorder characterized by progressive mental impairment, growth retardation, and spasticity and punctuated by sometimes fatal episodes of hyperammonemia. We constructed a knockout mouse strain carrying a nonfunctional AI gene by homologous recombination. Arginase AI knockout mice completely lacked liver arginase (AI) activity, exhibited severe symptoms of hyperammonemia, and died between postnatal days 10 and 14. During hyperammonemic crisis, plasma ammonia levels of these mice increased >10-fold compared to those for normal animals. Livers of AI-deficient animals showed hepatocyte abnormalities, including cell swelling and inclusions. Plasma amino acid analysis showed the mean arginine level in knockouts to be approximately fourfold greater than that for the wild type and threefold greater than that for heterozygotes; the mean proline level was approximately one-third and the ornithine level was one-half of the proline and ornithine levels, respectively, for wild-type or heterozygote mice--understandable biochemical consequences of arginase deficiency. Glutamic acid, citrulline, and histidine levels were about 1.5-fold higher than those seen in the phenotypically normal animals. Concentrations of the branched-chain amino acids valine, isoleucine, and leucine were 0.4 to 0.5 times the concentrations seen in phenotypically normal animals. In summary, the AI-deficient mouse duplicates several pathobiological aspects of the human condition and should prove to be a useful model for further study of the disease mechanism(s) and to explore treatment options, such as pharmaceutical administration of sodium phenylbutyrate and/or ornithine and development of gene therapy protocols.
| S-EPMC133904 | biostudies-literature
Project description:Arginase I (ARG1) deficiency is an autosomal recessive urea cycle disorder, caused by deficiency of the enzyme Arginase I, resulting in accumulation of arginine in blood. Current Standard of Care (SOC) for ARG1 deficiency in patients or those having detrimental mutations of ARG1 gene is diet control. Despite diet and drug therapy with nitrogen scavengers, ~25% of patients suffer from severe mental deficits and loss of ambulation. 75% of patients whose symptoms can be managed through diet therapy continue to suffer neuro-cognitive deficits. In our research, we demonstrate in vitro and in vivo that administration of ARG1 mRNA increased ARG1 protein expression and specific activity in relevant cell types, including ARG1-deficient patient cell lines, as well as in wild type mice for up to 4 days. These studies demonstrate that ARG1 mRNA treatment led to increased functional protein expression of ARG1 and subsequently an increase in urea. Hence, ARG1 mRNA therapy could be a potential treatment option to develop for patients.
| S-EPMC6161738 | biostudies-literature
Project description:Arginase deficiency is caused by deficiency of arginase 1 (ARG1), a urea cycle enzyme that converts arginine to ornithine. Clinical features of arginase deficiency include elevated plasma arginine levels, spastic diplegia, intellectual disability, seizures and growth deficiency. Unlike other urea cycle disorders, recurrent hyperammonemia is typically less severe in this disorder. Normalization of plasma arginine levels is the consensus treatment goal, because elevations of arginine and its metabolites are suspected to contribute to the neurologic features. Using data from patients enrolled in a natural history study conducted by the Urea Cycle Disorders Consortium, we found that 97% of plasma arginine levels in subjects with arginase deficiency were above the normal range despite conventional treatment. Recently, arginine-degrading enzymes have been used to deplete arginine as a therapeutic strategy in cancer. We tested whether one of these enzymes, a pegylated human recombinant arginase 1 (AEB1102), reduces plasma arginine in murine models of arginase deficiency. In neonatal and adult mice with arginase deficiency, AEB1102 reduced the plasma arginine after single and repeated doses. However, survival did not improve likely, because this pegylated enzyme does not enter hepatocytes and does not improve hyperammonemia that accounts for lethality. Although murine models required dosing every 48 h, studies in cynomolgus monkeys indicate that less frequent dosing may be possible in patients. Given that elevated plasma arginine rather than hyperammonemia is the major treatment challenge, we propose that AEB1102 may have therapeutic potential as an arginine-reducing agent in patients with arginase deficiency.
| S-EPMC5007608 | biostudies-literature
Project description:Marine biodiversity and derived ecosystem services are critical to the healthy functioning of marine ecosystems, and to human economic and societal well-being. Thus, an understanding of marine biodiversity in different ecosystems is necessary for their conservation and management. Coral reefs in particular are noted for their high levels of biodiversity, and among the world's coral reefs, the subtropical Ryukyu Islands (RYS; also known as the Nansei Islands) in Japan have been shown to harbor very high levels of marine biodiversity. This study provides an overview of the state of marine biodiversity research in the RYS. First, we examined the amount of English language scientific literature in the Web of Science (WoS; 1995-2017) on six selected representative taxa spanning protists to vertebrates across six geographic sub-regions in the RYS. Our results show clear taxonomic and sub-region bias, with research on Pisces, Cnidaria, and Crustacea to be much more common than on Dinoflagellata, Echinodermata, and Mollusca. Such research was more commonly conducted in sub-regions with larger human populations (Okinawa, Yaeyama). Additional analyses with the Ocean Biogeographic Information System (OBIS) records show that within sub-regions, records are concentrated in areas directly around marine research stations and institutes (if present), further showing geographical bias within sub-regions. While not surprising, the results indicate a need to address 'understudied' taxa in 'understudied sub-regions' (Tokara, Miyako, Yakutane, Amami Oshima), particularly sub-regions away from marine research stations. Second, we compared the numbers of English language scientific papers on eight ecological topics for the RYS with numbers from selected major coral reef regions of the world; the Caribbean (CAR), Great Barrier Reef (GBR), and the Red Sea (RES). As expected, the numbers for all topics in the RYS were well below numbers from all other regions, yet within this disparity, research in the RYS on 'marine protected areas' and 'herbivory' was an order of magnitude lower than numbers in other regions. Additionally, while manuscript numbers on the RYS have increased from 1995 to 2016, the rate of increase (4.0 times) was seen to be lower than those in the CAR, RES, and GBR (4.6-8.4 times). Coral reefs in the RYS feature high levels of both endemism and anthropogenic threats, and subsequently they contain a concentration of some of the world's most critically endangered marine species. To protect these threatened species and coral reef ecosystems, more data are needed to fill the research gaps identified in this study.
| S-EPMC6464027 | biostudies-literature