著者

Dorna Derakhshan Erfan Taherifard Ehsan Taherifard Sarvin Sajedianfard Ali Derakhshan

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.9, no.2, pp.109-112, 2020-05-31 (Released:2020-06-15)

参考文献数

23

被引用文献数

1

---

Immunodeficiency 10 is an autosomal recessive disorder presenting with iris hypoplasia, muscular hypotonia and nonprogressive myopathy, recurrent bacterial infections, autoimmune hemolytic anemia, hypohidrosis and nail dysplasia caused by the mutation of stromal interaction molecule 1 gene (STIM1). Herein, we present a new case of STIM1 mediated immunodeficiency, carrying a novel frameshift mutation. Our patient presented with nephrotic syndrome, hypotonia, myopathy, recurrent bacterial infections, thrombocytopenia and autoimmune hemolytic anemia. She is now 23 months old and is on steroid, cyclosporine and monthly IVIG. She has had no recent significant infections and is receiving rehabilitation therapy to improve her motor skills. Rare genetic syndromes should be suspected in patients of consanguineous parents, who present with a set of different manifestations. Gathering all the patient's manifestations together and looking them as one disease should be encouraged.

著者

Yanqin Lu Shie Zhang Yanzhou Wang Xiuzhi Ren Jinxiang Han

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.8, no.2, pp.98-107, 2019-05-31 (Released:2019-06-14)

参考文献数

110

被引用文献数

27

---

Type I collagen is an important structural protein of bone, skin, tendon, ligament and other connective tissues. It is initially synthesized as a precursor form, procollagen, consisting of two identical pro-α1(I) and one proα2(I) chains, encoded by COL1A1 and COL1A2, respectively. The N- and C- terminal propeptides of procollagen are cleavage by N-proteinase and C-proteinase correspondingly, to form the central triple helix structure with Gly-X-Y repeat units. Mutations of COL1A1 and COL1A2 genes are associated with osteogenesis imperfecta, some types of Ehlers-Danlos syndrome, Caffey diseases, and osteogenesis imperfect/Ehlers-Danlos syndrome overlapping diseases. Clinical symptoms caused by different variations can be variable or similar, mild to lethal, and vice versa. We reviewed the relationship between clinical manifestations and type I collagen – related rare genetic disorders and their possible molecular mechanisms for different mutations and disorders.

著者

Fatma Mujgan Sonmez Eyyup Uctepe Mehmet Gunduz Zeliha Gormez Seval Erpolat Murat Oznur Mahmut Samil Sagiroglu Huseyin Demirci Esra Gunduz

出版者

バイオ&ソーシャル・サイエンス推進国際研究交流会

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.5, no.3, pp.222-226, 2016 (Released:2016-09-05)

参考文献数

15

被引用文献数

13

---

Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, café-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better.

著者

Jun-ichi Satoh Yoshihiro Kino Motoaki Yanaizu Youhei Tosaki Kenji Sakai Tsuyoshi Ishida Yuko Saito

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

pp.2017.01073, (Released:2017-11-21)

参考文献数

30

被引用文献数

12 26

---

Nasu-Hakola disease (NHD) is a rare autosomal recessive leukoencephalopathy caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2 expressed in microglia. A rare variant of the TREM2 gene encoding p.Arg47His causes a 3-fold increase in the risk for late-onset Alzheimer's disease (LOAD). A recent study demonstrated that a rare coding variant p.Ser209Phe in the ABI family member 3 (ABI3) gene, a regulator of actin cytoskeleton organization, confers risk of developing of LOAD, although the pattern of ABI3 expression in AD and NHD brains with relevance to microglial pathology remains to be characterized. We investigated the cell type-specific expression of ABI3 in the brains derived from four non-neurological controls (NC), ten AD and five NHD cases by immunohistochemistry. We identified an intense ABI3 immunoreactivity chiefly on a subset of microglia with ramified or amoeboid morphology located in the grey matter and the white matter of the frontal cortex and the hippocampus of NC, AD, and NHD cases. The immunolabeled area of ABI3-positive microglia was not significantly different among NC, AD, and NHD cases due to great variability from case to case. The clusters of ABI3-immunoreactive microglia were found exclusively in AD brains and they were associated with amyloid plaques. Although these observations do not actively support the view that ABI3-immunoreactive microglia play a central role in the development of leukoencephalopathy in NHD brains and the neurodegeneration in AD brains, the intense expression of ABI3 on microglia might regulate their migration under conditions of health and disease in the central nervous system (CNS).

著者

Mohamad Moussa Athanasios G. Papatsoris Mohamad Abou Chakra Youssef Fares Baraa Dabboucy Athanasios Dellis

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.10, no.1, pp.1-10, 2021-02-28 (Released:2021-03-04)

参考文献数

95

被引用文献数

2 6

---

Spina bifida (SB) is a neurogenetic disorder with a complex etiology that involves genetic and environmental factors. SB can occur in two major forms of open SB or SB aperta and closed SB or SB occulta. Myelomeningocele (MMC), the most common neural tube defects (NTDs), occurs in approximately 1 in 1,000 births. Considering non-genetic factors, diminished folate status is the best-known factor influencing NTD risk. The methylenetetrahydrofolate reductase (MTHFR) gene has been implicated as a risk factor for NTDs. The primary disorder in the pathogenesis of MMC is failed neural tube closure in the embryonic spinal region. The clinical manifestation of SB depends on clinical type and severity. SB can be detected in the second trimester using ultrasound which will reveal specific cranial signs. The management of MMC traditionally involves surgery within 48 h of birth. Prenatal repair of MMC is recommended for fetuses who meet maternal and fetal Management of Myelomeningocele Study (MOMS) specified criteria. Urological manifestations of SB include urinary incontinence, urolithiasis, sexual dysfunction, renal dysfunction, and urinary tract infection. Renal failure is among the most severe complications of SB. The most important role of the urologist is the management of neurogenic bladder. Medical management with clean intermittent catheterization and anticholinergic treatment is generally considered the gold standard of therapy. However, when this therapy fails surgical reconstruction become the only remaining option. This review will summarize the pathogenesis, risk factors, genetic contribution, diagnostic test, and management of SB. Lastly, the urologic outcomes and therapies are reviewed.

著者

Alexandre Fabre Julien Mancini

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

pp.2022.01063, (Released:2022-07-22)

参考文献数

14

---

LUCA, the last universal common ancestor, is the hypothetical most recent common ancestor of the three domains of life which share the universal genes (UG). It seems interesting to evaluate whether the UG phylogeny has had an impact on current Human gene constraints. A list of human homologs of UG was retrieved from the eggNOG database. We analyzed this LUCA gene (LG) group, and a random sample of 500 genes from the gnomAD database (RG group). Gene constraint metrics were retrieved from gnomAD and associations with Mendelian diseases and modes of inheritance were retrieved from OMIM. The LG group consisted of 277 genes and the RG group, 492 (8 genes were in LG group). 38.6% of the genes in the LG group and 25.2% of the genes in the RG group were associated with a Mendelian disease (p < 0.0001). The mode of inheritance was more often autosomal recessive (69.0 vs. 50.5%), and less often autosomal dominant (19.0 vs. 31.3%), or mixed (6.0 vs. 12.1%) for those associated with the LG group (p = 0.048). The LG group was significantly more constrained for missense variants (MOEUF, 0.919 vs. 0.997, p < 0.0001) and was borderline significantly more constrained for loss-of-function variants (LOEUF, 0.872 vs. 0.947, p = 0.051). These results suggest that the UG in humans differs from the rest of the genome in terms of constraints and associated Mendelian diseases. It suggests that phylogenic data can explain some of the characteristics of human genes and could help in interpreting variants.

著者

Yanqin Lu Qingxia Gao Xiuzhi Ren Junfeng Li Dan Yang Zijian Zhang Jinxiang Han

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.11, no.3, pp.96-104, 2022-08-31 (Released:2022-09-17)

参考文献数

53

被引用文献数

8

---

The current study updated data on the incidence and prevalence of 121 rare diseases listed in China's First List of Rare Diseases to provide rationales and references for the development and promotion of rare-disease-related policies. The National Health Commission of the People's Republic of China issued the Rare Disease Diagnosis and Treatment Guide (2019) (denoted here as China's Rare Disease Diagnosis and Treatment Guide). Then 121 diseases were registered with the national rare disease diagnosis and treatment network. The incidence/prevalence of 121 rare diseases varied from country to country. Data are available for a total of 76 rare diseases (76 of 121 rare diseases, 62.81%) in China, including data on the incidence of 23 rare diseases (19.01%) and data on the prevalence of 66 (54.55%). There are data on the incidence/prevalence of 112 rare diseases (112 of 121 rare diseases, 92.56%) at the global level, including data on the incidence of 86 rare diseases (71.07%) and data on the prevalence of 91 (75.21%). On average, the incidence of progressive muscular dystrophies, hyperphenylalaninemia, citrullinemia, and methylmalonic acidemia is over 1/10,000 in China. The prevalence of coronary artery ectasia, congenital scoliosis, retinitis pigmentosa, severe congenital neutropenia, congenital hyperinsulinemic hypoglycemia, and osteogenesis imperfecta is over 1/10,000 in China. All of these figures are beyond the cut-off of 1/10,000 according to the 2021 definition of rare diseases in China. As registration and investigation of rare diseases continues, the spectrum of rare diseases in some provinces is expanding. Diseases such as idiopathic pulmonary arterial hypertension, hepatolenticular degeneration, hemophilia, amyotrophic lateral sclerosis, idiopathic pulmonary fibrosis, and multiple sclerosis are relatively prevalent in some regions and cities of China. Registration efforts promote the correction of incidence/prevalence data, development of orphan drugs, coverage by medical insurance, and development of clinical and diagnostic pathways.

著者

Katherine M. Morgan Shabbar Danish Zhenggang Xiong

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.11, no.1, pp.43-45, 2022-02-28 (Released:2022-03-08)

参考文献数

10

被引用文献数

2

---

Molecular alterations found in gliomas are now considered entity-defining features. The World Health Organization (WHO) classification system currently classifies the vast majority of gliomas utilizing an integrated genotype-phenotype approach. We present a case of diffuse astrocytoma with a mosaic isocitrate dehydrogenase (IDH)1-R132H-mutant immunophenotype and low subclonal allele frequency. A 35-year-old patient with a history of IDH1-R132H mutated diffuse astrocytoma in 20014 presented to the hospital again in 2019. MRI examination showed a non-enhancing abnormal signal in the periphery of her previous surgical cavity. Histopathological examination revealed that the tumor was hypercellular and without high grade histopathological features. The neoplastic cells were immunohistologically positive for GFAP, Olig2, and ATRX. However, only some scattered tumor cells were positive for IDH1-R132H. Cytogenetic studies revealed a lack of chromosomal 1p/19q co-deletion. Further next-generation sequencing (NGS) demonstrated a low-level IDH1-R132H mutation and allele frequency. Based on these findings, the diagnosis of diffuse astrocytoma with mosaic IDH1-R132H-mutant immunophenotype and low subclonal allele frequency (WHO grade II) was generated. This case indicates that gliomas may have heterogeneous molecular profile and the intra-tumoral molecular heterogeneity highlights the need to further characterize the molecular profile for glioma classification and clinical management.

著者

Ryohei Norioka Shinsuke Tobisawa Ryusei Nishigori Tomiko Kuhara Masahide Yazaki Masayoshi Nagao Toshihiro Ohura Yasuyuki Takai Asuka Funai Kazuhito Miyamoto Akihiro Kawata Kazushi Takahashi

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.10, no.2, pp.126-130, 2021-05-31 (Released:2021-06-03)

参考文献数

16

被引用文献数

3

---

We report a case of saccharopinuria with hyperammonemia and hypercitrullinemia in a Japanese woman who presented with elderly-onset epilepsy, progressive cognitive decline, and gait ataxia. Blood amino acid analysis revealed an increase in citrulline, cystine, and lysine levels, and urine amino acid analysis showed increased citrulline and cystine levels. Urine metabolomics revealed an increased saccharopine level, leading to the definitive diagnosis of saccharopinuria. In western blots of liver biopsy samples, normal citrin levels were observed, suggesting that adult-onset citrullinemia type 2 (CTLN2) was not present. In addition, decreased argininosuccinate synthetase (ASS) levels were observed, and ASS1 gene, a causative gene for citrullinemia type 1 (CTLN1), was analyzed, but no gene mutations were found. Because the causes of hypercitrullinemia were not clear, it might be secondary to saccharopinuria. Muscle biopsy findings of the biceps brachii revealed diminished cytochrome c oxidase (COX) activity, mitochondrial abnormalities on electron microscopy and p62-positive structures in immunohistochemical analyses. Saccharopinuria is generally considered a benign metabolic variant, but our case showed elevated lysine and saccharopine levels causing ornithine circuit damage, mitochondrial dysfunction, and autophagy disorders. This may lead to so far unknown neurological disorders.

著者

Taichi Imaizumi Akira Kumakura Keiko Yamamoto-Shimojima Yumko Ondo

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.7, no.4, pp.245-250, 2018-11-30 (Released:2018-12-17)

参考文献数

18

被引用文献数

10

---

Because biallelic SZT2 variants have been reported in patients with neurodevelopmental disorders associated with various degrees of developmental delay, intractable seizures, and distinctive features; this condition is recognized as an autosomal recessive disorder. Previously, eleven patients have been reported and most of them have compound heterozygous SZT2 variants, leading to premature termination. In these patients, all reported variants were unique and there were no common pathogenic variants identified. In this study, we identified a paternal uniparental disomy of chromosome 1 in a patient with a neurodevelopmental disorder associated with severe intellectual disability, intractable epilepsy, autistic features, distinctive features, and transient macrocephaly. This resulted in homozygous patterns through chromosome 1. Among the variants in chromosome 1, a rare SZT2 variant, NM_015284.3:c.6553C>T (p.Arg2185Trp), was selected as a powerful candidate variant in this patient. Although the clinical features of this patient are relatively milder than that reported previously, it may be derived from genetic heterogeneity. This is the first report of a homozygous missense SZT2 variant.

著者

Akamatsu Nobuhisa Sugawara Yasuhiko

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.1, no.2, pp.66-80, 2012

被引用文献数

4

---

Primary biliary cirrhosis (PBC) is an immune-mediated chronic progressive inflammatory liver disease, predominantly affecting middle-aged women, characterized by the presence of antimitochondrial antibodies (AMAs), which can lead to liver failure. Genetic contributions, environmental factors including chemical and infectious xenobiotics, autoimmunity and loss of tolerance have been aggressively investigated in the pathogenesis of PBC, however, the actual impact of these factors is still controversial. Survival of PBC patients has been largely improved with the widespread use of ursodeoxycholic acid (UDCA), however, one third of patients still do not respond to the treatment and proceed to liver cirrhosis, requiring liver transplantation as a last resort for cure. The outcome of liver transplantation is excellent with 5- and 10-year survival rates around 80% and 70%, respectively, while along with long survival, the recurrence of the disease has become an important outcome after liver transplantation. Prevalence rates of recurrent PBC rage widely between 1% and 35%, and seem to increase with longer follow-up. Center-specific issues, especially the use of protocol biopsy, affect the variety of incidence, yet, recurrence itself does not affect patient and graft survival at present, and retransplantation due to recurrent disease is extremely rare. With a longer follow-up, recurrent disease could have an impact on patient and graft survival.

著者

Xiaowei Jin Li Chen

出版者

バイオ&ソーシャル・サイエンス推進国際研究交流会

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.5, no.4, pp.308-313, 2016 (Released:2016-11-28)

参考文献数

24

被引用文献数

5

---

Of over 7,000 known rare diseases, only 5% currently have an available treatment option worldwide. Moreover, the vast majority of rare disease patients in China have no access to treatment due to limited availability and the lack of appropriate infrastructure in China's healthcare system. Despite increased interest in orphan drug development, drug companies in China with active programs on drugs to treat rare diseases are still limited. Hence, there is a huge unmet need in China, with over 10 million patients suffering from rare diseases. Nonetheless, this has created unprecedented opportunities for the Chinese drug development market. Life science innovation in China has recently received a healthy boost from the 13th National Five-Year Plan and from on-going reform of the China Food and Drug Administration (CFDA). Rare diseases are now recognized as a national priority with increasing governmental support, creating tremendous opportunities for both domestic and multinational drug companies. China is anticipated to play an increasingly important role in the global fight against rare diseases. To ensure future success, Chinese drug companies should leverage the valuable knowledge assembled over the past three decades by Western countries in the area of orphan drug development.

著者

Qaddra Fahada Ab. Rahman Nurul Farhana Jufri Asmah Hamid

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.12, no.1, pp.5-12, 2023-02-28 (Released:2023-03-04)

参考文献数

50

被引用文献数

4

---

Prader-Willi syndrome (PWS) is a rare genetic disorder due to lack of genes expression inherited from the paternal chromosome 15q11-q13 region usually from paternal deletions, maternal uniparental disomy 15 or imprinting defect. There are two different nutritional stages reported in an individual with PWS; first stage during infancy marked by feeding and growth difficulties and second stage where hyperphagia starts and leads to development of obesity. However, the exact mechanism of hyperphagia development, from having difficulties in feeding during early years to insatiable appetite after they grow is still unknown and is the focused in this review. The keywords used for literature search such as "Prader-Willi syndrome", "hyperphagia", "obesity", and "treatment" were used to create the search strings by using synonyms in order to retrieve the relevant records from PubMed, Scopus and Science Direct. The possible mechanism of hyperphagia can be classed into hormonal abnormalities such as increase in ghrelin and leptin from infancy to adulthood. Low level of hormones was observed in the thyroid, insulin and peptide YY at certain ages. Neuronal abnormalities contributed by Orexin A and brain structure alteration was documented at 4-30 years old. Treatment in the form of drugs such as livoletide, topiramate, and diazoxide could potentially alleviate these abnormalities and make hyperphagia less prominent in PWS. The approaches are important to regulate the hormonal changes and neuronal involvement as potentially controlling hyperphagia and obesity.

著者

Mohamad Moussa Mohamad Abou Chakra Athanasios G. Papatsoris Baraa Dabboucy Michael Hsieh Athanasios Dellis Youssef Fares

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.10, no.2, pp.62-74, 2021-05-31 (Released:2021-06-03)

参考文献数

99

被引用文献数

2

---

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Lower urinary tract dysfunction due to MS includes a dysfunction of the storage phase or dysfunction of the voiding phase or a detrusor-sphincter dyssynergia. Baseline evaluation includes a voiding chart, an ultrasound scan of the urinary tract, urine culture, and an urodynamic study. For storage symptoms, antimuscarinics are the first-line treatment, and clean intermittent catheterization (CIC) is indicated if there is concomitant incomplete bladder emptying. Intradetrusor injections with botulinum toxin A (BTX-A), are recommended for refractory cases. Urinary diversion is rarely indicated. For patients with voiding symptoms, CIC and alpha-blockers are usually offered. Sexual dysfunction in patients with MS is multifactorial. Phosphodiesterase type 5 inhibitors are first-line therapies for MS-associated erectile dysfunction in both male and female patients. This review summarizes the epidemiology, pathogenesis, risk factors, genetic, clinical manifestations, diagnostic tests, and management of MS. Lastly, the urologic outcomes and therapies are reviewed.

著者

Zhiye Ying Li Gong Chunyang Li

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

pp.2021.01027, (Released:2021-06-01)

参考文献数

21

被引用文献数

8

---

Over the past few years, China has paid greater attention to the topic of rare diseases. The Chinese Government has made considerable efforts to gradually improve the situation of patients with rare diseases in terms of diagnosis and treatment, access to medication, and affordability of care. The National Health Commission implemented a raft of measures, including the first Catalog of Rare Diseases, establishment of a rare diseases alliance, establishment of the Network for Collaboration in Rare Disease Diagnosis and Treatment, formulation of the Guidelines for the Diagnosis and Treatment of Rare Diseases, sharing of diagnostic and treatment information, and creation of expert committees, to ensure the standardization of rare disease diagnosis and treatment and to promote the improvement of rare disease diagnosis and treatment capabilities nationwide. In order to encourage the research, development, and production of drugs to treat rare diseases, the National Medical Products Administration has drafted a series of policies to accelerate the review and approval of drug registration and to support the research and development of drugs to treat rare diseases. The Ministry of Finance has also helped to implement tax incentives for drugs to treat rare diseases, to encourage the marketing and importation of drugs to treat rare diseases, and to reduce the cost of drugs for patients with rare diseases. Through adjustment of the List of Drugs Covered by National Medical Insurance, the National Healthcare Security Administration has covered an increasing number of drugs to treat rare diseases under basic medical insurance. It has also negotiated to reduce the price of some drugs to treat rare diseases, further reducing the economic burden on patients with rare diseases.

著者

Jiahao Hu Lin Zhu Jiangjiang He Dingguo Li Qi Kang Chunlin Jin

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

pp.2021.01091, (Released:2021-07-30)

参考文献数

31

被引用文献数

1

---

Lysosomal storage diseases (LSDs) are a group of rare diseases that cause progressive physical dysfunction and organ failure, which significantly affected patients' quality of life. The objective of this study was to explore the characteristics and usage of Enzyme Replacement Treatments (ERTs), which is the only specific therapy for LSDs, of patients with the four different LSDs (Gaucher, Fabry, Pompe disease and Mucopolysaccharidosis) in Shanghai, and then evaluate the economic burden and quality of life of these patients. A total of 31patients, involving 5, 14, 4 and 8 patients with Gaucher, Fabry, Pompe disease and Mucopolysaccharidosis, respectively, were included in analysis. The result showed that only five Gaucher disease (GD) patients in Shanghai used Imiglucerase in 2019, while the other 26 patients with the other three LSDs did not receive ERTs. The total health expenditure of GD patients was 2,273,000CNY on average mainly resulted by the high cost of Imiglucerase. The total health expenditure of the other 26 patients was 37,765CNY on average. Though the cost-sharing mechanism between basic medical insurance, charity fund and patients had been explored for Gaucher disease in Shanghai, the out-of-pocket part, which was 164,301 CNY, still laid a heavy economic burden on the patients and their families. The mean EQ-VAS score of GD patients was 76.4 ± 15.5, which was higher than that of the other three LSDs. It is recommended that the scope of drug reimbursement list and the reimbursement level should be further expanded and raised to help improve the living conditions of patients with LSDs.

著者

Deborah Ribeiro Nascimento Suzana Lopes Bomfim Balaniuc Durval Batista Palhares Adam Underwood Marilene Garcia Palhares Fabiana Alves Francisco Oliveira Vieira Elaine Maria Souza-Fagundes Liane De Rosso Giuliani Paula Cristhina Niz Xavier Helen Lima Del Puerto Robson Augusto Souza Santos Amy Milsted Jose Mauro Brum Iandara Schettert Silva Almir Sousa Martins

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

pp.2021.01012, (Released:2021-05-22)

参考文献数

54

---

Fibrodysplasia Ossificans Progressiva (FOP) is a rare congenital intractable disease associated with a mutation in ACVR1 gene, characterized by skeleton malformations. Ascorbic acid (AA) and propranolol (PP) in combination is reported to minimize flare-ups in patients. FOP leukocyte phenotype may possibly be modulated by AA and PP treatment. In this study, expression of 22 potential target genes was analyzed by RT-PCR in peripheral blood mononuclear cells culture (PBMC) from FOP patients and controls to determine effectiveness of the combination therapy. PBMC were treated with AA, PP and AA+PP combination. Basal expression of 12 of the 22 genes in FOP PBMC was statistically different from controls. ACVR1, ADCY2, ADCY9 and COL3 were downregulated while COL1 was upregulated. ADRB1, ADRB2, RUNX2, TNF-α and ACTB, were all overexpressed in FOP PBMC. In control, AA upregulated COL1, SVCT1, ACTB, AGTR2 and downregulated ADCY2. In FOP cells, AA upregulated ACVR1, BMP4, COL1, COL3, TNF-α, ADCY2, ADCY9, AGTR2 and MAS, while downregulated ADBR2, RUNX2, ADCY1, SVCT1 and ACTB. PP increased ADBR1 and decreased RUNX2, TNF-α, AGTR1, ACTB and CHRNA7 genes in treated control PBMC compared to untreated. PP upregulated ADBR1, ADBR2 and MAS, and downregulated TNF-α and ACTB in treated FOP PBMC versus untreated. AA+PP augmented ADRB1 and ADRB2 expressions in control PBMC. In FOP PBMC, AA+PP augmented ACVR1, COL1, COL3, ADBR1, AGTR2 and MAS expression and downregulated ADBR2, RUNX2, ACTB and MRGD. These data show distinct gene expression modulation in leukocytes from FOP patients when treated with AA and or PP.

著者

Haowen Tang Peipei Song Zhiqiang Wang Bing Han Xiangfei Meng Yingwei Pan Xuan Meng Weidong Duan

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

pp.2020.03005, (Released:2020-04-13)

参考文献数

58

被引用文献数

9

---

Extrahepatic portosystemic shunt belongs to a family of rare vascular abnormalities. The clinical importance and manifestations of this vascular abnormality range from asymptomatic cases to liver or metabolic dysfunctions of various degrees. Congenital extrahepatic portosystemic shunt, also termed as Abernethy malformation, is a very rare congenital vascular malformation in which splenomesenteric blood drains into a systemic vein, bypassing the liver through a complete or partial extrahepatic shunt. So far, limited cases of congenital extrahepatic portosystemic shunt have been reported. In this review, incidence, mechanisms, complications, diagnoses and treatments of congenital extrahepatic portosystemic shunt are described.

著者

Mohamad Moussa Mohamad Abou Chakra Yasmin Moussa

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

pp.2019.01130, (Released:2020-02-04)

参考文献数

39

被引用文献数

3

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Peyronie's disease (PD) is a connective tissue disorder of the penis characterized by fibrosis and plaque formation within the tunica albuginea. PD is characterized by painful penile curvature that impairs sexual intercourse. Stem cell therapy is one of the recent non-invasive treatment options for patients with PD and it has promising results. Stem cells are undifferentiated cells that are capable of self-renewal and differentiation, promoting the repair of tissues via their immunomodulatory and anti-inflammatory action. Adipose-derived stem cells (ADSC) are used most widely due to their abundant tissue source and ease of isolation. Multiple studies have indicated the efficacy of stem cell therapy as a potential treatment for fibrotic diseases. Clearly, ADSCs may represent a way to treat and prevent PD in both rat and human models. Further clinical studies are needed to confirm the efficacy of stem cell therapy for PD in humans.

著者

Reymundo Lozano Atoosa Azarang Tanaporn Wilaisakditipakorn Randi J Hagerman

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.5, no.3, pp.145-157, 2016 (Released:2016-09-05)

参考文献数

150

被引用文献数

13 70

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The fragile X mental retardation 1 gene, which codes for the fragile X mental retardation 1 protein, usually has 5 to 40 CGG repeats in the 5' untranslated promoter. The full mutation is the almost always the cause of fragile X syndrome (FXS). The prevalence of FXS is about 1 in 4,000 to 1 in 7,000 in the general population although the prevalence varies in different regions of the world. FXS is the most common inherited cause of intellectual disability and autism. The understanding of the neurobiology of FXS has led to many targeted treatments, but none have cured this disorder. The treatment of the medical problems and associated behaviors remain the most useful intervention for children with FXS. In this review, we focus on the non-pharmacological and pharmacological management of medical and behavioral problems associated with FXS as well as current recommendations for follow-up and surveillance.