Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.138
Filtrar
2.
Talanta ; 209: 120558, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892015

RESUMO

Cystinosis is an autosomal recessive disorder characterized by the accumulation of cystine in lysosomes, causing irreversible damage to organs, especially the kidneys. Intracellular leukocyte cystine concentrations are used to diagnose cystinosis and to monitor cysteamine treatment. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method without derivatization capable of measuring leukocyte intracellular cystine concentrations. During development, the effects of using three different protein precipitation agents were evaluated in terms of sensitivity and the matrix effect, with 12% trichloroacetic acid providing the highest sensitivity. The effects of different blood collection tubes were also assessed in terms of recovery, matrix effect, and protein content. Compared to other methods, our method was quicker (run time of 3 min), was linear over the range 0.078-100 µM, and had lower limits of detection (0.0192 µM) and quantification (0.0582 µM). The intra-day and inter-day reproducibility %CVs were ≤10%. and the method had excellent recovery rates (94%-106%). Other parameters including matrix selectivity, injection carryover, leukocyte lysate stability were also validated and met the acceptance criterias of European Medicines Agency (EMA) Guideline. The assay was successfully applied to quantify cystine leukocyte concentration in healthy and cystinosis patients.


Assuntos
Cistina/análise , Cistinose/diagnóstico , Leucócitos/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Cistinose/sangue , Humanos , Limite de Detecção
3.
Muscle Nerve ; 61(1): 74-80, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31588568

RESUMO

BACKGROUND: Nephropathic cystinosis is a lysosomal storage disorder. Patient survival years after renal transplantation has revealed systemic complications including distal myopathy and dysphagia. METHODS: We evaluated 20 adult patients with nephropathic cystinosis using patient-reported and clinical outcome measures. Standard motor measures, video fluoroscopy swallow studies, and tests of respiratory function were performed. We also used Rasch analysis of an initial survey to design a 16-item survey focused on upper and lower extremity function, which was completed by 31 additional patients. RESULTS: Distal myopathy and dysphagia were common in patients with nephropathic cystinosis. Muscle weakness ranges from mild involvement of intrinsic hand muscles to prominent distal greater than proximal weakness and contractures. CONCLUSIONS: In addition to further characterization of underlying dysphagia and muscle weakness, we propose a new psychometrically devised, disease specific, functional outcome measures for distal myopathy in patients with nephropathic cystinosis.


Assuntos
Cistinose/complicações , Miopatias Distais/diagnóstico , Adulto , Cistinose/psicologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Miopatias Distais/etiologia , Miopatias Distais/psicologia , Extremidades/fisiopatologia , Feminino , Mãos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Exame Neurológico , Psicometria , Testes de Função Respiratória , Autorrelato , Resultado do Tratamento , Adulto Jovem
4.
PLoS One ; 14(12): e0223954, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800572

RESUMO

BACKGROUND: Cystinosis is a rare disorder caused by recessive mutations of the CTNS gene. Current therapy decreases cystine accumulation, thus slowing organ deterioration without reversing renal Fanconi syndrome or preventing eventual need for a kidney transplant.15-20% of cystinosis patients harbour at least one nonsense mutation in CTNS, leading to premature end of translation of the transcript. Aminoglycosides have been shown to permit translational read-through but have high toxicity level, especially in the kidney and inner ear. ELX-02, a modified aminoglycoside, retains it read-through ability without the toxicity. METHODS AND FINDINGS: We ascertained the toxicity of ELX-02 in cells and in mice as well as the effect of ELX-02 on translational read-through of nonsense mutations in cystinotic mice and human cells. ELX-02 was not toxic in vitro or in vivo, and permitted read-through of nonsense mutations in cystinotic mice and human cells. CONCLUSIONS: ELX-02 has translational read-through activity and produces a functional CTNS protein, as evidenced by reduced cystine accumulation. This reduction is comparable to cysteamine treatment. ELX-02 accumulates in the kidney but neither cytotoxicity nor nephrotoxicity was observed.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/fisiologia , Aminoglicosídeos/farmacologia , Cistina/metabolismo , Cistinose/tratamento farmacológico , Lisossomos/metabolismo , Mutação , Animais , Transporte Biológico , Cistinose/metabolismo , Cistinose/patologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Biossíntese de Proteínas
5.
J Pediatr Endocrinol Metab ; 32(10): 1187-1191, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31600138

RESUMO

Background Short stature is a common presentation in paediatric practice. Rickets can lead to poor growth and finding the underlying cause of rickets can, at times, be challenging. Case presentation The child was initially referred due to parental concerns of delayed walking, bowed legs, waddling gait and faltering growth. She was noted to have features of rickets. Bone profile and renal functions were reported to be within the normal range, however, on later review it was noted that adult values for inorganic phosphate had been given for reference ranges. Following a series of investigations, the underlying diagnosis for all her problems was made. Discussion This case demonstrates the complex diagnostic journey of a child whose presentation was not typical of the rare disorder. Unusually, the patient had no symptoms of polyuria or polydipsia and urine osmolality was normal.


Assuntos
Cisteamina/administração & dosagem , Cistinose/diagnóstico , Nanismo/diagnóstico , Raquitismo/diagnóstico , Pré-Escolar , Eliminadores de Cistina/administração & dosagem , Cistinose/complicações , Cistinose/tratamento farmacológico , Diagnóstico Diferencial , Nanismo/complicações , Feminino , Humanos , Prognóstico , Raquitismo/complicações
6.
Spec Care Dentist ; 39(6): 631-635, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31661163

RESUMO

Cystinosis is a rare autosomal recessive lysosomal storage disorder, which leads to abnormal accumulation of cysteine in various organs, including progressive dysfunction of kidneys. The most severe and frequent form, affecting ∼95% of patients, is termed infantile nephropathic cystinosis (NC) (OMIM 219800). We have reported oral findings in two patients with NC and described esthetic and functional rehabilitation in one of them. The first case describes a 16-year-old male patient, who was diagnosed with NC when he was 1-year-old. The patient exhibited generalized enamel hypoplasia, grade 1 drug-induced gingival overgrowth, caries lesion in molar tooth and supernumerary tooth (ie, distomolar). The second case describes a 14-year-old male patient diagnosed with NC at 3 years old. Clinical examination revealed generalized enamel hypoplasia and grade 1 drug-induced gingival overgrowth. Radiographic examination showed supernumerary tooth (mesiodens). The treatment included gingivoplasty and restoration with direct composite resin. The severity of hypoplasia highlights the importance of a dental rehabilitation treatment, as proposed here. Direct restoration with composite resin allowed harmony, function, and esthetics to be restored, in addition to being a rapid and low-cost technique.


Assuntos
Cistinose , Cárie Dentária , Adolescente , Pré-Escolar , Humanos , Lactente , Masculino
7.
Am J Case Rep ; 20: 1308-1313, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31481649

RESUMO

BACKGROUND Infantile nephropathic cystinosis is the most common and severe variant of cystinosis, which is a rare autosomal recessive condition related to a defect in the transportation of the protein cystine resulting in its deposition in various organs. Due to the rarity of this condition, only 1 case with extensive ocular involvement has been found in the English-language literature. Here, we report a second such case to highlight the significance of early diagnosis in avoiding devastating but preventable vision loss. CASE REPORT We describe the extensive asymmetrical ocular involvement in a 22-year-old woman who had nephropathic cystinosis since childhood. Despite frequent follow up and systemic and topical cysteamine therapy, she developed ocular complications, including increased intraocular pressure, uveitis, and retinal changes with complete loss of vision in her left eye. In addition, her general condition requires a renal transplant in the near future. CONCLUSIONS Ophthalmologists should be aware of cystinosis and the sequalae of ocular involvement in this disease, despite its rarity. Identification of the earliest corneal deposits should not be overlooked, especially in the context of other systemic manifestations that are indicative of the nephropathic variant of cystinosis.


Assuntos
Cegueira/etiologia , Cistinose/complicações , Hipertensão Ocular/etiologia , Uveíte/etiologia , Feminino , Humanos , Adulto Jovem
8.
Indian J Pathol Microbiol ; 62(3): 457-460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31361240

RESUMO

Nephropathic cystinosis is a rare autosomal recessive lysosomal disease characterized by accumulation of pathognomonic cystine crystals in renal and other tissues of the body. Cystinosis is caused by mutant cystinosin, the cystine transport protein located in lysosomal membranes, leading to systemic deposits of cystine and resultant end organ damage. Cystinosis is rarer in Asians than Caucasians with only a handful of cases reported from India to date. Due to its extreme rarity and clinically insidious presentation in contrast to the infantile form, the diagnosis of juvenile nephropathic cystinosis is frequently delayed or overlooked. Moreover, routine processing and sectioning of paraffin embedded tissues dissolves cystine crystals, making it difficult to diagnose this condition on light microscopic examination alone, mandating electron microscopic (EM) analysis of renal biopsies for an accurate diagnosis of this condition. We describe a case of juvenile nephropathic cystinosis presenting with uveitis and photophobia in a 17-year-old Indian male, diagnosed after EM examination of the patient's renal biopsy for evaluation of nephrotic syndrome. While highlighting the diagnostic utility of EM, we describe a few histopathologic clues which can prompt inclusion of EM analysis of renal biopsies in this setting.


Assuntos
Cistinose/diagnóstico , Síndrome Nefrótica/diagnóstico , Uveíte/diagnóstico , Adolescente , Sistemas de Transporte de Aminoácidos Neutros/genética , Biópsia , Cistina/metabolismo , Cistinose/genética , Humanos , Rim/patologia , Rim/ultraestrutura , Masculino , Microscopia Eletrônica , Síndrome Nefrótica/genética , Fotofobia/etiologia , Transtornos da Visão/etiologia
9.
Brain Cogn ; 135: 103578, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31233961

RESUMO

Cystinosis is a rare genetic lysosomal storage disorder characterized by the accumulation of cystine in lysosomes. Many organ systems are vulnerable to this cystine accumulation including the CNS. A past study demonstrated that children with cystinosis have deficits in visual learning and memory while their verbal learning and memory and global intellectual function are spared (Spilkin, Ballantyne, & Trauner, 2009). However, no related study has been performed to assess the dissociation between visual and verbal learning and memory in adults with cystinosis who have had the benefit of longterm treatment with the cystine-depleting agent, cysteamine. In this study we assessed visual and verbal learning and memory in 15 adults with cystinosis, with a mean age of 30.2 years. The results indicate that adults with cystinosis have no significant deficits in either verbal or visual learning and memory. However, the individuals did perform better on the verbal assessment. The results suggest that if early and continued treatment is given to individuals with cystinosis there is a relative sparing of visual learning and memory that might have otherwise declined. This emphasizes the essential nature of the proper clinical management of cystinosis.


Assuntos
Cistinose/psicologia , Memória/fisiologia , Aprendizagem Verbal/fisiologia , Adulto , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Aprendizagem Espacial/fisiologia
11.
Digit J Ophthalmol ; 25(1): 12-15, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31080371

RESUMO

Cystinosis, a rare autosomal recessive lysosomal storage disease, can be difficult to detect. The most common form of the disease is infantile or nephropathic cystinosis. Crystals can accumulate in the eye as early as 1 year of age. Early recognition and prompt investigations prevent further accumulation of cystine and resultant end-organ injury. The disease is usually confirmed through biochemical and genetic testing, which can be time consuming. Looking for cystine corneal deposits remains an important diagnostic criterion and is the least invasive test to perform. It is recommended that ophthalmic manifestations of cystinosis be confirmed by an ophthalmologist. We describe the case of a 3-year-old girl who presented with worsening emesis, pyrexia, and lethargy, and was diagnosed with infantile cystinosis. This case is used to present a technique that can facilitate the preliminary search for corneal cystine crystals by using equipment as readily available as two smartphones. The technique may be easily used in a variety of settings, including hospitals, clinics, and primary care centers where there is delayed or difficult access to ophthalmologists.


Assuntos
Doenças da Córnea/diagnóstico por imagem , Cistinose/complicações , Técnicas de Diagnóstico Oftalmológico/instrumentação , Smartphone , Pré-Escolar , Feminino , Humanos
12.
Ophthalmic Genet ; 40(2): 157-160, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30957593

RESUMO

BACKGROUND: Ocular cystinosis is a rare autosomal recessive disorder caused by one severe and one mild mutation in the CTNS gene. It is characterised by cystine deposition within the cornea and conjunctiva however, the kidneys are not affected. We report a case of ocular cystinosis caused by two potentially severe CTNS mutations and discuss the possible mechanism of renal sparing. METHODS: This is an observational case report of the proband and her unaffected relatives. All subjects underwent ophthalmic examination, whilst in the proband, In vivo laser scanning confocal microscopy was used to demonstrate cystine crystals within her corneas and conjunctiva. Genetic diagnosis was confirmed by DNA sequencing of the proband and the segregation of the mutations was established in her relatives. RT-PCR of leukocyte RNA was undertaken to determine if aberrant splicing of the CTNS gene was taking place Results: The proband was found to have cystine crystals limited to the anterior corneal stroma and the conjunctiva. Sequencing of the proband's CTNS gene found her to be a compound heterozygote for a 27bp deletion in exon8/intron 8 (c.559_561 + 24del) and a novel c.635C>T variant in exon 9 that is predicted be pathogenic and to result in the substitution of alanine with valine at amino acid position 212 (p.Ala212Val), which is within the 3rd transmembrane spanning domain of the CTNS protein. Examination of the proband's leukocyte RNA failed to demonstrate any aberrant CTNS gene splicing. CONCLUSION: We present a case of ocular cystinosis caused by two potentially severe CTNS gene mutations. The lack of renal involvement may be due to localised (ocular) aberrant CTNS RNA splicing.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Doenças da Túnica Conjuntiva/genética , Doenças da Córnea/genética , Cistinose/genética , Mutação , Adulto , Doenças da Túnica Conjuntiva/diagnóstico , Doenças da Córnea/diagnóstico , Cistinose/diagnóstico , Feminino , Estudos de Associação Genética , Heterozigoto , Humanos , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Linhagem , Processamento de RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Microscopia com Lâmpada de Fenda
13.
Transplant Proc ; 51(2): 545-547, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879586

RESUMO

BACKGROUND: Cystinosis is a rare genetic disorder characterized by the abnormal accumulation of cystine in the lysosomes of various tissues and organs leading to their dysfunction. The most common type is the infantile nephropathic cystinosis which without treatment leads to renal failure and before the introduction of cysteamine was the cause of death before puberty. CASE PRESENTATION: A 27-year-old female patient with infantile cystinosis developed end-stage renal disease at the age of 10. The first kidney transplantation from patient's father was carried out at the age of 12. The recurrent urinary tract infections led to the graft failure after 6 years. Following the removal of right appendages due to the ovarian tumor, the patient underwent the second kidney transplantation from her mother at the age of 19. After the transplantation, the cysteamine treatment was irregular due to limited availability of the medicine. When it became regular in 2017 the patient did not tolerate full doses. Despite elevated blood levels of cystine and the removal of right appendages, the patient naturally became pregnant in August 2017. Except for recurrent urinary tract infections, the renal parameters remained normal throughout the entire pregnancy. However, in the 32nd week of gestation, due to preeclampsia a caesarean section was performed. A healthy daughter was born, 1400/41 and with a 9 point Apgar score. CONCLUSIONS: Due to the possibility of treatment with cysteamine and kidney transplantations, patients with cystinosis live longer and their quality of life improves. These female patients can even naturally become pregnant and give birth to healthy children.


Assuntos
Cistinose , Complicações na Gravidez , Adulto , Cesárea , Cisteamina/uso terapêutico , Eliminadores de Cistina/uso terapêutico , Cistinose/terapia , Feminino , Humanos , Transplante de Rim , Gravidez , Resultado da Gravidez
14.
J Pediatr Endocrinol Metab ; 32(4): 375-382, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30849045

RESUMO

Background Cystinosis is a rare autosomal-recessive disorder caused by a defective transport of cystine across the lysosomal membrane. Previous studies have mapped cystinosis to the CTNS gene which is located on chromosome 17p13, and various CTNS mutations have been identified to correlate them with this disease. Methods We analyzed six patients from five unrelated families who were diagnosed with cystinosis in our hospital. We described the diagnostic procedures for all the patients and proposed alternative therapies for cystinosis patients instead of using cysteamine, an orphan drug which was commercially unavailable in China. Moreover, genetic analysis of all patients' samples was carried out to identify novel CTNS gene mutations. Results and conclusions The patients in this study were followed up from 1 to more than 10 years to monitor their growth and development, which indicated that the alternative therapies we used were helpful to ameliorate the complications of the cystinosis patients without cysteamine. Furthermore, by sequencing the patients' genome, we identified novel mutations in the CTNS gene including: c.477C > G (p.S159R), c.274C > T (p.Q92X) and c.680A > T (p.E227V); these mutations were only observed in cystinosis patients and had never been reported in any other populations, suggesting they might be specific to Chinese cystinosis patients.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Cistinose/diagnóstico , Genética Populacional , Mutação , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Cistinose/tratamento farmacológico , Cistinose/epidemiologia , Cistinose/genética , Feminino , Seguimentos , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Lactente , Masculino , Linhagem , Prognóstico
15.
J. bras. nefrol ; 41(1): 131-141, Jan.-Mar. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1002426

RESUMO

Abstract Care for patients with chronic and rare diseases is complex, especially considering the lack of knowledge about the disease, which makes early and precise diagnosis difficult, as well as the need for specific tests, sometimes of high complexity and cost. Added to these factors are difficulties in obtaining adequate treatment when available, in raising patient and family awareness about the disease and treatment compliance. Nephropathic cystinosis is among these diseases. After more than 20 years as a care center for these patients, the authors propose a follow-up protocol, which has been used with improvement in the quality of care and consists of a multidisciplinary approach, including care provided by a physician, nurse, psychologist, nutritionist and social worker. In this paper, each field objectively exposes how to address points that involve the stages of diagnosis and its communication with the patient and their relatives or guardians, covering the particularities of the disease and the treatment, the impact on the lives of patients and families, the approach to psychological and social issues and guidelines on medications and diets. This protocol could be adapted to the follow-up of patients with other rare diseases, including those with renal involvement. This proposal is expected to reach the largest number of professionals involved in the follow-up of these patients, strengthening the bases for the creation of a national protocol, observing the particularities of each case.


Resumo A assistência a pacientes com doenças crônicas e raras é complexa, principalmente pela falta de disseminação de conhecimento sobre a doença, o que dificulta o diagnóstico preciso e precoce, além da necessidade da realização de exames específicos, por vezes de alta complexidade e custo. Somam-se a esses fatores dificuldades na obtenção de tratamento adequado quando disponível, na conscientização do paciente e da família sobre a doença e na aderência ao tratamento. A cistinose nefropática está entre essas doenças. Após mais de 20 anos como centro de atendimento a esses pacientes, os autores propõem um protocolo de seguimento, o qual vem sendo empregado com melhora na qualidade da assistência e consiste de uma abordagem multidisciplinar, incluindo, principalmente, atendimento prestado por médico, enfermeiro, psicólogo, nutricionista e assistente social. Neste artigo, cada área expõe de maneira objetiva como abordar pontos que envolvem as etapas do diagnóstico e sua comunicação ao paciente e a seus familiares ou responsáveis, abrangendo as particularidades da doença e do tratamento, o impacto na vida do paciente e de sua família, a abordagem das questões psicológicas e sociais e orientações quanto a medicamentos e dietas. Considera-se que este protocolo poderia ser adaptado ao seguimento de pacientes portadores de outras doenças raras, incluindo aquelas com envolvimento renal. Com essa proposta, espera-se alcançar o maior número de profissionais envolvidos no seguimento desses pacientes, fortalecendo as bases para a criação de um protocolo nacional, observando-se as particularidades de cada caso.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Adulto Jovem , Cistinose/diagnóstico , Cistinose/terapia , Doenças Raras/diagnóstico , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/tratamento farmacológico , Equipe de Assistência ao Paciente , Gravidez , Protocolos Clínicos , Diálise Renal , Transplante de Rim , Resultado do Tratamento , Cistinose/complicações , Cistinose/psicologia , Doenças Raras/complicações , Doenças Raras/psicologia , Doenças Raras/tratamento farmacológico , Diálise , Síndrome de Fanconi/complicações , Síndrome de Fanconi/psicologia , Falência Renal Crônica/etiologia
16.
Am J Pathol ; 189(5): 1053-1064, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30794806

RESUMO

Cystinosis is a rare lysosomal storage disorder caused by loss-of-function mutations of the CTNS gene, encoding cystinosin, a symporter that mediates cystine efflux from lysosomes. Approximately 95% of patients with cystinosis display renal Fanconi syndrome, short stature, osteopenia, and rickets. In this study, we investigated whether the absence of cystinosin primarily affects bone remodeling activity, apart from the influences of the Fanconi syndrome on bone mineral metabolism. Using micro-computed tomography and histomorphometric and bone serum biomarker analysis, we evaluated the bone phenotype of 1-month-old Ctns-/- knockout (KO) male mice without tubulopathy. An in vitro study was performed to characterize the effects of cystinosin deficiency on osteoblasts and osteoclasts. Micro-computed tomography analysis showed a reduction of trabecular bone volume, bone mineral density, and number and thickness in KO mice compared with wild-type animals; histomorphometric analysis revealed a reduction of osteoblast and osteoclast parameters in tibiae of cystinotic mice. Decreased levels of serum procollagen type 1 amino-terminal propeptide and tartrate-resistant acid phosphatase in KO mice confirmed reduced bone remodeling activity. In vitro experiments showed an impairment of Ctns-/- osteoblasts and osteoclasts. In conclusion, cystinosin deficiency primarily affects bone cells, leading to a bone loss phenotype of KO mice, independent from renal failure.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/fisiologia , Doenças Ósseas/patologia , Cistinose/patologia , Osteoblastos/patologia , Osteogênese , Animais , Doenças Ósseas/etiologia , Doenças Ósseas/metabolismo , Cistinose/etiologia , Cistinose/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoblastos/metabolismo
17.
Mol Genet Metab ; 126(4): 413-415, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30685240

RESUMO

INTRODUCTION: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene. Patients with nephropathic cystinosis suffer not only from renal disease but have also other systemic complications like myopathy and swallowing dysfunction. Dysphagia for solid food is mentioned in patients with cystinosis, but in clinical practice swallowing investigations are only performed when the patient has complaints. The aim of this study was to explore the swallowing function in patients with cystinosis by use of the Test of Mastication and Swallowing Solids (TOMASS), and to compare their performance with patients with myotonic dystrophy type 1 - a neuromuscular disease in which dysphagia for solid food is a known problem. METHODS: Twenty adult patients with cystinosis (11 men and 9 women, range 19-51 years) and 10 patients with myotonic dystrophy type 1 (5 men and 5 women, range 20-60 years) were included. All cystinosis patients were treated with cysteamine. Data of the two groups were compared with normative data using independent-samples t-tests. In case the variables were not normally distributed, the non-parametric Mann-Whitney U test was used. RESULTS: There was a significant difference in the number of bites, masticatory cycles, swallows and total time between the normal values and cystinosis patients. The results of the cystinosis patients were comparable to those of the patients with myotonic dystrophy. DISCUSSION AND CONCLUSION: Adult patients with cystinosis have significant dysphagia for solid food. Clinicians treating these patients should be aware of this fact. The TOMASS can be performed easily in clinical practice to investigate whether patients with cystinosis have swallowing dysfunction. The swallowing dysfunction can now be diagnosed by use of a non-invasive, very simple, non-harmful test. It can be discussed whether this should be added to the regular care scheme of cystinosis patients in order to regularly follow-up swallowing function.


Assuntos
Cistinose/complicações , Transtornos de Deglutição/etiologia , Deglutição , Nefropatias/complicações , Adulto , Cisteamina/uso terapêutico , Cistinose/tratamento farmacológico , Feminino , Humanos , Masculino , Mastigação , Pessoa de Meia-Idade , Distrofia Miotônica/complicações , Adulto Jovem
19.
Curr Eye Res ; 44(5): 497-504, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30624086

RESUMO

PURPOSE: To examine if current development on using contact lenses for drug delivery of cysteamine to treat ocular symptoms of cystinosis can be tinted to mitigate photophobia common in patients by reducing transmittance Methods: Commercial contact lenses were placed in a carbon black solution to examine loading after lens synthesis. Silicone hydrogel contact lenses were also synthesized with carbon black added prior to UV curing. Transmittance was measured using UV-vis spectrophotometry over the range of 190-1190 nm and compared to unmodified contact lenses. Lens parameters of refractive index, ion permeability, and Young's modulus were measured using a refractometer, release of sodium chloride, and the cantilever method. Cysteamine release was measured by loading lenses into 5% cysteamine solution and then monitoring the release of the drug using UV-vis spectrophotometry. Vitamin E diffusion barriers were also added to lenses via ethanol solution, and the release of cysteamine from these modified lenses was also examined. RESULTS: No leeching of carbon black was detected during experiments. Loading of pre-made contact lenses led to uneven distribution of carbon black throughout lens. Adding 0.3% carbon black to lens monomer solution prior to UV-curing led to even distribution and a transmittance reduction of approximately 50%. Ion permeability was reduced from 6.19 ± 0.90 x 10-3 to 1.28 ± 0.06 x 10-3 mm2 min-1, and Young's modulus was decreased from 1.58 ± 0.08 to 1.29 ± 0.06 MPa. Cysteamine releases from carbon black lenses with and without vitamin E were comparable to controls, although the loading solution of vitamin E/ethanol had to be tripled to achieve a similar mass loading to control. CONCLUSIONS: Carbon black increases the softness of contact lenses, but a loading of 0.3% maintains lens parameters required for wear. The release of cysteamine is also possible with carbon black lenses, albeit requiring a higher loading concentration of vitamin E to achieve similar release times.


Assuntos
Lentes de Contato Hidrofílicas , Doenças da Córnea/metabolismo , Eliminadores de Cistina/farmacocinética , Cistinose/metabolismo , Sistemas de Liberação de Medicamentos , Fotofobia/prevenção & controle , Fuligem/química , Animais , Anti-Hipertensivos/farmacocinética , Doenças da Córnea/tratamento farmacológico , Cisteamina/farmacocinética , Cisteamina/uso terapêutico , Eliminadores de Cistina/uso terapêutico , Cistinose/tratamento farmacológico , Módulo de Elasticidade , Microscopia Eletrônica de Varredura , Coelhos , Refratometria , Espectrofotometria Ultravioleta , Timolol/farmacocinética , Vitamina E/administração & dosagem , Vitaminas/administração & dosagem
20.
J Bras Nefrol ; 41(1): 131-141, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30465592

RESUMO

Care for patients with chronic and rare diseases is complex, especially considering the lack of knowledge about the disease, which makes early and precise diagnosis difficult, as well as the need for specific tests, sometimes of high complexity and cost. Added to these factors are difficulties in obtaining adequate treatment when available, in raising patient and family awareness about the disease and treatment compliance. Nephropathic cystinosis is among these diseases. After more than 20 years as a care center for these patients, the authors propose a follow-up protocol, which has been used with improvement in the quality of care and consists of a multidisciplinary approach, including care provided by a physician, nurse, psychologist, nutritionist and social worker. In this paper, each field objectively exposes how to address points that involve the stages of diagnosis and its communication with the patient and their relatives or guardians, covering the particularities of the disease and the treatment, the impact on the lives of patients and families, the approach to psychological and social issues and guidelines on medications and diets. This protocol could be adapted to the follow-up of patients with other rare diseases, including those with renal involvement. This proposal is expected to reach the largest number of professionals involved in the follow-up of these patients, strengthening the bases for the creation of a national protocol, observing the particularities of each case.


Assuntos
Cistinose/diagnóstico , Cistinose/tratamento farmacológico , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/tratamento farmacológico , Doenças Raras/diagnóstico , Doenças Raras/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Protocolos Clínicos , Cistinose/complicações , Cistinose/psicologia , Diálise , Síndrome de Fanconi/complicações , Síndrome de Fanconi/psicologia , Feminino , Humanos , Lactente , Recém-Nascido , Falência Renal Crônica/etiologia , Transplante de Rim , Masculino , Equipe de Assistência ao Paciente , Gravidez , Doenças Raras/complicações , Doenças Raras/psicologia , Diálise Renal , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA