Pub Date : 2023-06-05DOI: 10.29245/2572-9411/2023/1.1207
M. Pauni, Cecilia Mazzuzz, G. Agosta
Spinal muscular atrophy (SMA) is a rare, but severe disease, which is characterized by progressive muscular weakness resulting in permanent assisted ventilation before the age of 2. Supportive care used to be the only available treatment. However, relevant progress has been achieved with the approval of nusinersen (an antisense oligonucleotide modulating SMN2 splicing), which changed the disease outcome for many patients. Thus, management of SMA patients requires a multidisciplinary approach with pharmacological and non-pharmacological treatments to provide the necessary supportive care for symptom management, nutritional support and active rehabilitation to optimize muscle function. In this paper we aimed to report the first patient with type 1 SMA in the Latin America region that was able to get off the ventilator without a tracheostomy after an early treatment with nusinersen, continuing to date stable and with no need of ventilatory support.
{"title":"Survival without Permanent Respiratory Support in a Patient with SMA Type 1 Treated with Nusinersen","authors":"M. Pauni, Cecilia Mazzuzz, G. Agosta","doi":"10.29245/2572-9411/2023/1.1207","DOIUrl":"https://doi.org/10.29245/2572-9411/2023/1.1207","url":null,"abstract":"Spinal muscular atrophy (SMA) is a rare, but severe disease, which is characterized by progressive muscular weakness resulting in permanent assisted ventilation before the age of 2. Supportive care used to be the only available treatment. However, relevant progress has been achieved with the approval of nusinersen (an antisense oligonucleotide modulating SMN2 splicing), which changed the disease outcome for many patients. Thus, management of SMA patients requires a multidisciplinary approach with pharmacological and non-pharmacological treatments to provide the necessary supportive care for symptom management, nutritional support and active rehabilitation to optimize muscle function. In this paper we aimed to report the first patient with type 1 SMA in the Latin America region that was able to get off the ventilator without a tracheostomy after an early treatment with nusinersen, continuing to date stable and with no need of ventilatory support.","PeriodicalId":118703,"journal":{"name":"Journal of Rare Diseases Research & Treatment","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127080496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-18DOI: 10.29245/2572-9411/2023/1.1208
P. Krall, J. Grandy, Lillian Bolte, J. Salgado, F. Cavagnaro, C. González, J. Luis Guerrero
Background Cystinosis is a rare disease caused by CTNS gene defects. The main clinical presentations are nephropathic infantile cystinosis (NIC) and nephropathic juvenile cystinosis (NJC); both develop chronic kidney disease (CKD) and extrarenal complications. Opportune diagnosis and access to therapy are challenging in developing countries. Methods To describe the clinical and genetic profile in all cystinosis patients known to be diagnosed in Chile, we performed a retrospective review of the medical records of those patients diagnosed from 1994 to 2022. Age at diagnosis, glomerular filtration rate, metabolic variables, anthropometric values, access to treatment, outcomes, and genetic results were analyzed. Results Nine patients (8NIC/1NJC) were diagnosed. Patients with NIC had a median age of 16.5 (IQR 13-23) months at diagnosis, and two patients died during follow-up. Most of the patients started cysteamine therapy up to 5 months after diagnosis and reached CKD stages 3-4 within four years. During the follow-up, all but one of the NIC patients showed height for age Z-score values between -1.5 and -4.0. Two patients received kidney transplants, and one of them remains functional after 15 years. The single NJC was a 21-year-old female patient who received irregular cysteamine therapy and rapidly reached CKD stage 5. Genetic testing was positive in 7/7 cases, being del57kb the predominant variant (10/14 alleles). Conclusions Developing countries face many challenges in providing adequate healthcare. Our findings show clinical and diagnostic aspects to the medical and patient community that might contribute to the diagnostic approach and treatment access for cystinosis in Chile. Opportune genetic testing may facilitate early diagnosis that is known to be associated with a better prognosis.
{"title":"Clinical and Genetic Characterization of Cystinosis: Unmet Healthcare Needs in a Cohort Study from a Developing Country","authors":"P. Krall, J. Grandy, Lillian Bolte, J. Salgado, F. Cavagnaro, C. González, J. Luis Guerrero","doi":"10.29245/2572-9411/2023/1.1208","DOIUrl":"https://doi.org/10.29245/2572-9411/2023/1.1208","url":null,"abstract":"Background Cystinosis is a rare disease caused by CTNS gene defects. The main clinical presentations are nephropathic infantile cystinosis (NIC) and nephropathic juvenile cystinosis (NJC); both develop chronic kidney disease (CKD) and extrarenal complications. Opportune diagnosis and access to therapy are challenging in developing countries. Methods To describe the clinical and genetic profile in all cystinosis patients known to be diagnosed in Chile, we performed a retrospective review of the medical records of those patients diagnosed from 1994 to 2022. Age at diagnosis, glomerular filtration rate, metabolic variables, anthropometric values, access to treatment, outcomes, and genetic results were analyzed. Results Nine patients (8NIC/1NJC) were diagnosed. Patients with NIC had a median age of 16.5 (IQR 13-23) months at diagnosis, and two patients died during follow-up. Most of the patients started cysteamine therapy up to 5 months after diagnosis and reached CKD stages 3-4 within four years. During the follow-up, all but one of the NIC patients showed height for age Z-score values between -1.5 and -4.0. Two patients received kidney transplants, and one of them remains functional after 15 years. The single NJC was a 21-year-old female patient who received irregular cysteamine therapy and rapidly reached CKD stage 5. Genetic testing was positive in 7/7 cases, being del57kb the predominant variant (10/14 alleles). Conclusions Developing countries face many challenges in providing adequate healthcare. Our findings show clinical and diagnostic aspects to the medical and patient community that might contribute to the diagnostic approach and treatment access for cystinosis in Chile. Opportune genetic testing may facilitate early diagnosis that is known to be associated with a better prognosis.","PeriodicalId":118703,"journal":{"name":"Journal of Rare Diseases Research & Treatment","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117018028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angelman syndrome is the consequence of a genetic alteration in the chromosome 15 where the expression of the β3-subunits of GABA-A receptors is encoded. So, unpredictable responses to intravenous GABA-anesthetics may be the result. We present a 19-year-old male patient with AS who required anesthesia to undergo an MRI and CT-scan. All his previous anesthetic procedures were complicated by severe emergence agitation with physical self-injury. His parents also mentioned that the patient reacted with paradoxical agitation due to benzodiazepines (midazolam) administration in previous anesthesia. Dexmedetomidine (an α-2- adrenergic agonist) has been used in pediatric anesthesia as an adjuvant to attenuate agitation events after inhalation anesthesia. However, there are few publications on its use in patients with AS. We describe the use of a single intravenous dose of dexmedetomidine (0.2μg/Kg) to prevent sevoflurane-related emergence agitation with good results.In addition, the potential benefits and precautions in using this non-GABA drug in patients with AS are discussed.
{"title":"The Use of Dexmedetomidine for The Prevention of Sevoflurane Related Emergence Agitation in a Patient with Angelman Syndrome Who Underwent General Anesthesia for Magnetic Resonance Imaging. “Case Report”.","authors":"C. Ramírez-Paesano, Camila Carrasco Chacón, Claudia Rodiera Clarens, osep Rodiera Olive","doi":"10.29245/2572-9411/2022/3.1207","DOIUrl":"https://doi.org/10.29245/2572-9411/2022/3.1207","url":null,"abstract":"Angelman syndrome is the consequence of a genetic alteration in the chromosome 15 where the expression of the β3-subunits of GABA-A receptors is encoded. So, unpredictable responses to intravenous GABA-anesthetics may be the result. We present a 19-year-old male patient with AS who required anesthesia to undergo an MRI and CT-scan. All his previous anesthetic procedures were complicated by severe emergence agitation with physical self-injury. His parents also mentioned that the patient reacted with paradoxical agitation due to benzodiazepines (midazolam) administration in previous anesthesia. Dexmedetomidine (an α-2- adrenergic agonist) has been used in pediatric anesthesia as an adjuvant to attenuate agitation events after inhalation anesthesia. However, there are few publications on its use in patients with AS. We describe the use of a single intravenous dose of dexmedetomidine (0.2μg/Kg) to prevent sevoflurane-related emergence agitation with good results.In addition, the potential benefits and precautions in using this non-GABA drug in patients with AS are discussed.","PeriodicalId":118703,"journal":{"name":"Journal of Rare Diseases Research & Treatment","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130859932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-20DOI: 10.29245/2572-9411/2022/2.1204
Tran M Nguyen, Matt Downs, N. Bennett, Vitaliy Matyushenko, Harumasa Nakamura, D. Osredkar, Shiwen Wu, N. Goemans, A. Ambrosini, Rahsa El Sherifc, C. Campbell
Background: TREAT-NMD is a global neuromuscular (NM) organization, created to enhance infrastructure to facilitate novel therapeutics reaching patients. One main activity is aimed at supporting NM disease registries. These rare disease registries are useful to fill knowledge gaps for various stakeholders in the disease community using real world data. Although it is important to understand how patient data is being utilized in the TREAT-NMD network and other rare disease registries, there is no systematic process or consistent metric for documenting the academic output from these registries. Objectives: The objective of this study was to determine the academic output from NM registries associated with the TREAT-NMD network, and the types of research the data is facilitating. Results: A systematic search of EMBASE, Medline, Cochrane Central and SCOPUS was performed from inception to November 24, 2021. The search yielded a total of 650 results, with 231 full text studies assessed for eligibility and a total of 97 studies that met the inclusion criteria. Conclusions: The results suggest publications from TREAT-NMD are mainly descriptive or methodologic. Rare disease registries, like the TREAT-NMD network, would benefit from clear and consistent metrics to facilitate reporting of academic output.
{"title":"Academic Productivity from Rare Neuromuscular Disease Registries: A Systematic Review","authors":"Tran M Nguyen, Matt Downs, N. Bennett, Vitaliy Matyushenko, Harumasa Nakamura, D. Osredkar, Shiwen Wu, N. Goemans, A. Ambrosini, Rahsa El Sherifc, C. Campbell","doi":"10.29245/2572-9411/2022/2.1204","DOIUrl":"https://doi.org/10.29245/2572-9411/2022/2.1204","url":null,"abstract":"Background: TREAT-NMD is a global neuromuscular (NM) organization, created to enhance infrastructure to facilitate novel therapeutics reaching patients. One main activity is aimed at supporting NM disease registries. These rare disease registries are useful to fill knowledge gaps for various stakeholders in the disease community using real world data. Although it is important to understand how patient data is being utilized in the TREAT-NMD network and other rare disease registries, there is no systematic process or consistent metric for documenting the academic output from these registries. Objectives: The objective of this study was to determine the academic output from NM registries associated with the TREAT-NMD network, and the types of research the data is facilitating. Results: A systematic search of EMBASE, Medline, Cochrane Central and SCOPUS was performed from inception to November 24, 2021. The search yielded a total of 650 results, with 231 full text studies assessed for eligibility and a total of 97 studies that met the inclusion criteria. Conclusions: The results suggest publications from TREAT-NMD are mainly descriptive or methodologic. Rare disease registries, like the TREAT-NMD network, would benefit from clear and consistent metrics to facilitate reporting of academic output.","PeriodicalId":118703,"journal":{"name":"Journal of Rare Diseases Research & Treatment","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131117762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-01DOI: 10.29245/2572-9411/2022/2.1206
Shahid Ullah, A. Tonks, Asif Ullah Khan, Abdulsalam Muharrab Alruwaili, M. Lodhi
Case presentation Prolidase enzyme plays a crucial role in proline-rich proteins metabolism and physiological processes such as inflammation, cell proliferation, wound healing, angiogenesis, and carcinogenesis. Due to mutations in the peptidase D (PEPD) gene, the catalytic activity of prolidase loss results in prolidase deficiency. Deficiency of prolidase enzyme is an autosomal inborn metabolic rare genetic disorder that has neither any proper treatment nor consensus for treatment. With approximately 100 cases recorded worldwide, the submitted manuscript describes the 2nd recorded case of prolidase deficiency, an extremely uncommon autosomal recessive disorder associated with collagen metabolism, in a 15-year-old Pakistan boy. The disorder typically becomes apparent during infancy. Affected individuals may have enlargement of the spleen (splenomegaly); in some cases, both the spleen and liver are enlarged (hepatosplenomegaly). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Here we present the report of a 15-year-old boy who has all the clinical manifestations of deficiency of prolidase. This is the 2nd case in Pakistan's 229,488,994 million population.
{"title":"A Case report of rare disease Prolidase deficiency in a 15-year-old Pakistan boy","authors":"Shahid Ullah, A. Tonks, Asif Ullah Khan, Abdulsalam Muharrab Alruwaili, M. Lodhi","doi":"10.29245/2572-9411/2022/2.1206","DOIUrl":"https://doi.org/10.29245/2572-9411/2022/2.1206","url":null,"abstract":"Case presentation Prolidase enzyme plays a crucial role in proline-rich proteins metabolism and physiological processes such as inflammation, cell proliferation, wound healing, angiogenesis, and carcinogenesis. Due to mutations in the peptidase D (PEPD) gene, the catalytic activity of prolidase loss results in prolidase deficiency. Deficiency of prolidase enzyme is an autosomal inborn metabolic rare genetic disorder that has neither any proper treatment nor consensus for treatment. With approximately 100 cases recorded worldwide, the submitted manuscript describes the 2nd recorded case of prolidase deficiency, an extremely uncommon autosomal recessive disorder associated with collagen metabolism, in a 15-year-old Pakistan boy. The disorder typically becomes apparent during infancy. Affected individuals may have enlargement of the spleen (splenomegaly); in some cases, both the spleen and liver are enlarged (hepatosplenomegaly). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Here we present the report of a 15-year-old boy who has all the clinical manifestations of deficiency of prolidase. This is the 2nd case in Pakistan's 229,488,994 million population.","PeriodicalId":118703,"journal":{"name":"Journal of Rare Diseases Research & Treatment","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123913466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-25DOI: 10.29245/2572-9411/2022/1.1205
M. T. Passos, Patrícia Varela, D. E. Fernandes, M. G. Polito, J. Pesquero, G. Kirsztajn
Introduction: Focal segmental glomerulosclerosis (FSGS) can be caused by mutations in the genes NPHS2, ACTN4, TRPC6, and INF2 among others, presenting variable levels of proteinuria, including nephrotic syndrome, that frequently progress to end-stage renal disease (ESRD). The establishment of the genotype-phenotype correlation caused by mutations in genes expressed in the podocyte could contribute to understanding their role in FSGS and to the decision-making in the clinical setting in similar cases. Methods: Genomic DNA was extracted from peripheral blood of the proband, his brother, sister and mother. All the exons of the genes NPHS2, ACTN4, TRPC6, and INF2 were amplified by a polymerase chain reaction, purified, and sequenced by the Sanger method. The presence of variants was evaluated in the proband with FSGS and relatives, reviewed, and annotated using dbSNP and HGMD. Results: In the clinical evaluation, the proband and his brother presented childhood-onset nephrotic syndrome, added with renal biopsies confirming FSGS, which was resistant to steroid and other immunosuppressive drugs, and progressed to ESRD. Both patients showed the variants p.P316S in NPHS2 and p.G894S in ACTN4, as well as the polymorphism p.R229Q in NPHS2, all variants in heterozygosis. Their parents were healthy, and the mother presented only the variant p.P316S in NPHS2 in heterozygosis. Conclusions: The family members with FSGS had a combination of the variants p.P316S and p.R229Q in NPHS2, and p.G894S in ACTN4, shared similar clinical presentation, nephrotic syndrome with onset in late childhood that rapidly progressed to ESRD.
{"title":"Effect of combined NPHS2 and ACTN4 variants in the onset and severity of focal segmental glomerulosclerosis","authors":"M. T. Passos, Patrícia Varela, D. E. Fernandes, M. G. Polito, J. Pesquero, G. Kirsztajn","doi":"10.29245/2572-9411/2022/1.1205","DOIUrl":"https://doi.org/10.29245/2572-9411/2022/1.1205","url":null,"abstract":"Introduction: Focal segmental glomerulosclerosis (FSGS) can be caused by mutations in the genes NPHS2, ACTN4, TRPC6, and INF2 among others, presenting variable levels of proteinuria, including nephrotic syndrome, that frequently progress to end-stage renal disease (ESRD). The establishment of the genotype-phenotype correlation caused by mutations in genes expressed in the podocyte could contribute to understanding their role in FSGS and to the decision-making in the clinical setting in similar cases. Methods: Genomic DNA was extracted from peripheral blood of the proband, his brother, sister and mother. All the exons of the genes NPHS2, ACTN4, TRPC6, and INF2 were amplified by a polymerase chain reaction, purified, and sequenced by the Sanger method. The presence of variants was evaluated in the proband with FSGS and relatives, reviewed, and annotated using dbSNP and HGMD. Results: In the clinical evaluation, the proband and his brother presented childhood-onset nephrotic syndrome, added with renal biopsies confirming FSGS, which was resistant to steroid and other immunosuppressive drugs, and progressed to ESRD. Both patients showed the variants p.P316S in NPHS2 and p.G894S in ACTN4, as well as the polymorphism p.R229Q in NPHS2, all variants in heterozygosis. Their parents were healthy, and the mother presented only the variant p.P316S in NPHS2 in heterozygosis. Conclusions: The family members with FSGS had a combination of the variants p.P316S and p.R229Q in NPHS2, and p.G894S in ACTN4, shared similar clinical presentation, nephrotic syndrome with onset in late childhood that rapidly progressed to ESRD.","PeriodicalId":118703,"journal":{"name":"Journal of Rare Diseases Research & Treatment","volume":"111 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133196663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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