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1.
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
2.
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
3.
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
5.
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
6.
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
7.
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
8.
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
9.
Pediatr Nephrol ; 34(4): 571-578, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29260317

RESUMO

Cystinosis is a rare autosomal-recessive lysosomal storage disease with high morbidity and mortality. It is caused by mutations in the CTNS gene that encodes the cystine transporter, cystinosin, which leads to lysosomal cystine accumulation. Patients with infantile nephropathic cystinosis, the most common and most severe clinical form of cystinosis, commonly present with renal Fanconi syndrome by 6-12 months of age, and without specific treatment, almost all will develop end-stage renal disease (ESRD) by 10-12 years of age. Early corneal cystine crystal deposition is a hallmark of the disease. Cystinosis also presents with gastrointestinal symptoms (e.g., vomiting, decreased appetite, and feeding difficulties) and severe growth retardation and may affect several other organs over time, including the eye, thyroid gland, gonads, pancreas, muscles, bone marrow, liver, nervous system, lungs, and bones. Cystine-depleting therapy with cysteamine orally is the only specific targeted therapy available for managing cystinosis and needs to be combined with cysteamine eye drops for corneal disease involvement. In patients with early treatment initiation and good compliance to therapy, long-term cysteamine treatment delays progression to ESRD, significantly improves growth, decreases the frequency and severity of extrarenal complications, and is associated with extended life expectancy. Therefore, early diagnosis of cystinosis and adequate life-long treatment with cysteamine are essential for preventing end-organ damage and improving the overall prognosis in these patients.


Assuntos
Cisteamina/administração & dosagem , Eliminadores de Cistina/administração & dosagem , Cistinose/tratamento farmacológico , Sistemas de Transporte de Aminoácidos Neutros/genética , Cisteamina/efeitos adversos , Eliminadores de Cistina/efeitos adversos , Cistinose/complicações , Cistinose/diagnóstico , Cistinose/genética , Progressão da Doença , Esquema de Medicação , Predisposição Genética para Doença , Humanos , Mutação , Fatores de Tempo , Resultado do Tratamento
10.
Int Ophthalmol ; 39(6): 1413-1418, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29916124

RESUMO

PURPOSE: Cystinosis is an autosomal recessive inherited lysosomal storage disease with an incidence of 1:100.000 up to 1:200.000 caused by a gene mutation of a lysosomal transport protein resulting in deposition of cystine in lysosomes in all cells and tissues. In the cornea, crystalline, gold-dust deposition of cystine leads to visual impairment, recurrent erosions, photophobia, epiphora and blepharospasmus. Standard therapy is topical and systemic application of cysteamine which may resolve the accumulated cystine crystals. PATIENT AND METHODS: This is a case report of a thirty-one-year-old patient who already underwent renal transplantation because of nephropathic cystinosis. Visual impairment by cystine crystal deposition was aggravated by a central avascular pannus formation in his right eye. Penetrating keratoplasty was performed in intention to improve the patient's visual acuity and life quality. RESULTS: After penetrating keratoplasty in the right eye, there was only a slight visual improvement. OCT scans of the macula revealed intraretinal cystine crystals and a cystoid macular edema, which was treated with a bevacizumab injection. Transmission electron microscopy of the excised cornea revealed spiky intracorneal inclusions and confocal in vivo microscopy of the left eye allowed detailed visualization of the cystine crystal deposition. CONCLUSIONS: There is a variability of ocular manifestations of nephropathic cystinosis. Ophthalmologists have a central role in the early diagnosis of cystinosis as mostly the first manifestation are cystine crystals in the cornea. Penetrating keratoplasty may be one of the therapeutical options. Nevertheless, the patient has to be informed about the limited prognosis because of the persisting underlying disease.


Assuntos
Doenças da Córnea/etiologia , Cistinose/complicações , Adulto , Inibidores da Angiogênese/uso terapêutico , Humanos , Ceratoplastia Penetrante , Edema Macular/tratamento farmacológico , Masculino , Resultado do Tratamento
11.
Adv Chronic Kidney Dis ; 25(4): 351-357, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30139461

RESUMO

Proximal renal tubular acidosis (pRTA) is an inherited or acquired clinical syndrome in which there is a decreased bicarbonate reclamation in the proximal tubule resulting in normal anion gap hyperchloremic metabolic acidosis. In children, pRTA may be isolated but is often associated with a general proximal tubular dysfunction known as Fanconi syndrome which frequently heralds an underlying systemic disorder from which it arises. When accompanied by Fanconi syndrome, pRTA is characterized by additional renal wasting of phosphate, glucose, uric acid, and amino acids. The most common cause of inherited Fanconi syndrome in the pediatric age group is cystinosis, a disease with therapeutic implications. In this article, we summarize the clinical presentation and differential diagnosis of pRTA and Fanconi syndrome and provide a practical approach to their evaluation in children.


Assuntos
Acidose Tubular Renal/diagnóstico , Acidose Tubular Renal/etiologia , Síndrome de Fanconi/etiologia , Acidose Tubular Renal/tratamento farmacológico , Acidose Tubular Renal/genética , Criança , Cistinose/complicações , Doença de Dent/complicações , Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/genética , Humanos , Túbulos Renais Proximais , Síndrome Oculocerebrorrenal/complicações
12.
J Bone Miner Res ; 33(10): 1870-1880, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29905968

RESUMO

Nephropathic cystinosis is a rare lysosomal storage disorder. Patients present in the first year of life with renal Fanconi syndrome that evolves to progressive chronic kidney disease (CKD). Despite the multiple risk factors for bone disease, the frequency and severity of skeletal disorders in nephropathic cystinosis have not been described. We performed systematic bone and mineral evaluations of subjects with cystinosis seen at the NIH (n = 30), including history and physical examination, serum and urine biochemistries, DXA, vertebral fracture assessment, skeletal radiographs, and renal ultrasound. Additionally, histomorphometric analyses are reported on six subjects seen at the UCLA Bone and Mineral Metabolism Clinic. In NIH subjects, mean age was 20 years (range, 5 to 44 years), 60% were CKD stages G1 to G4, and 40% had a renal transplant. Mean bone mineral density (BMD) Z-scores were decreased in the femoral neck, total hip, and 1/3 radius (p < 0.05). Low bone mass at one or more sites was present in 46% of subjects. Twenty-seven percent of subjects reported one or more long bone fractures. Thirty-two percent of subjects had incidental vertebral fractures, which were unrelated to transplant status. Long-bone deformity/bowing was present in 64%; 50% had scoliosis. Diffuse osteosclerosis was present in 21% of evaluated subjects. Risk factors included CKD, phosphate wasting, hypercalciuria, secondary hyperparathyroidism, hypovitaminosis D, male hypogonadism, metabolic acidosis, and glucocorticoid/immunosuppressive therapy. Sixty-one percent of the non-transplanted subjects had ultrasonographic evidence of nephrocalcinosis or nephrolithiasis. Histomorphometric analyses showed impaired mineralization in four of six studied subjects. We conclude that skeletal deformities, decreased bone mass, and vertebral fractures are common and relevant complications of nephropathic cystinosis, even before renal transplantation. Efforts to minimize risk factors for skeletal disease include optimizing mineral metabolism and hormonal status, combined with monitoring for nephrocalcinosis/nephrolithiasis. © 2018 This article is a U.S. Government work and is in the public domain in the USA.


Assuntos
Osso e Ossos/patologia , Cistinose/complicações , Nefropatias/complicações , Adolescente , Adulto , Biópsia , Densidade Óssea , Calcificação Fisiológica , Criança , Pré-Escolar , Feminino , Fraturas Ósseas/etiologia , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Masculino , Fatores de Risco , Adulto Jovem
13.
Iran J Kidney Dis ; 12(1): 61-63, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29421779

RESUMO

Cystinosis is a rare autosomal recessive disorder resulting from defective lysosomal transport of cystine due to mutations in the cystinosin lysosomal cystine transporter (CTNS) gene. The clinical phenotype of nephropathic cystinosis is characterized by renal tubular Fanconi syndrome and development of end-stage renal disease during the first decade. Although metabolic acidosis is the classically prominent finding of the disease, a few cases may present with hypokalemic metabolic alkalosis mimicking Bartter syndrome. Bartter-like presentation may lead to delay in diagnosis and initiation of specific treatment for cystinosis. We report a case of a 6-year-old girl initially presenting with the features of Bartter syndrome that was diagnosed 2 years later with nephropathic cystinosis and a novel CTNS mutation.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Síndrome de Bartter/diagnóstico , Cistinose/diagnóstico , Cistinose/genética , Mutação , Alcalose/etiologia , Criança , Cistinose/complicações , Cistinose/terapia , Análise Mutacional de DNA , Diagnóstico Diferencial , Progressão da Doença , Feminino , Predisposição Genética para Doença , Humanos , Hipopotassemia/etiologia , Falência Renal Crônica/etiologia , Diálise Peritoneal , Fenótipo , Valor Preditivo dos Testes
14.
Pediatr Nephrol ; 33(7): 1165-1172, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29435659

RESUMO

BACKGROUND: Bone impairment appears to be a novel complication of nephropathic cystinosis despite cysteamine therapy. Its exact underlying pathophysiology is nevertheless unclear. The objective of this study was to evaluate bone status among patients included in the French Crystobs study. METHODS: In addition to clinical data, bone status was evaluated using biomarkers (ALP, PTH, 25-D, 1-25D, FGF23), DXA (spine and total body), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius. Results were compared to age- and gender-matched healthy controls (1:2 basis) from the local reference cohorts. RESULTS: At a median age of 22.5 (10.2-34.6) years, 10 patients with nephropathic cystinosis were included (2 receiving conservative therapies, 2 undergoing hemodialysis, 6 with a past of renal transplantation); 7 out of 10 patients complained of a bone symptom (past of fracture, bone deformations, and/or bone pain). Biochemicals and spine DXA did not show any significant abnormalities. Using HR-pQCT, significant decreases in cortical parameters (e.g., cortical thickness 850 (520-1100) versus 1225 (480-1680) µm; p < 0.05) and total volumetric bone mineral density (290 (233-360) versus 323 (232-406) mg/cm3; p < 0.05) were observed in cystinotic patients in comparison to controls at the tibia. There were no differences for trabecular parameters. Similar results were observed at the radius. CONCLUSIONS: In this pilot study, bone impairment (rather cortical than trabecular) is a significant clinical problem in nephropathic cystinosis; 70% of patients displayed significant bone symptoms, during teenage or young adulthood. This new complication should be known by physicians because of its potential dramatic impact on quality of life.


Assuntos
Densidade Óssea , Doenças Ósseas/diagnóstico , Osso Cortical/fisiopatologia , Cistinose/complicações , Absorciometria de Fóton , Adolescente , Adulto , Fatores Etários , Biomarcadores/análise , Doenças Ósseas/epidemiologia , Doenças Ósseas/etiologia , Doenças Ósseas/fisiopatologia , Criança , Osso Cortical/diagnóstico por imagem , Cisteamina , Cistinose/tratamento farmacológico , Feminino , Humanos , Masculino , Projetos Piloto , Prevalência , Estudos Prospectivos , Qualidade de Vida , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/fisiopatologia , Índice de Gravidade de Doença , Tíbia/diagnóstico por imagem , Tíbia/fisiopatologia , Tomografia Computadorizada por Raios X , Adulto Jovem
15.
Nephrol Dial Transplant ; 33(9): 1525-1532, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29365190

RESUMO

Background: Bone impairment is a poorly described complication of nephropathic cystinosis (NC). The objectives of this study were to evaluate in vitro effects of cystinosin (CTNS) mutations on bone resorption and of cysteamine treatment on bone cells [namely human osteoclasts (OCs) and murine osteoblasts]. Methods: Human OCs were differentiated from peripheral blood mononuclear cells (PBMCs) of patients and healthy donors (HDs). Cells were treated with increasing doses of cysteamine in PBMCs or on mature OCs to evaluate its impact on differentiation and resorption, respectively. Similarly, cysteamine-treated osteoblasts derived from murine mesenchymal stem cells were assessed for differentiation and activity with toxicity and proliferation assays. Results: CTNS was expressed in human OCs derived from HDs; its expression was regulated during monocyte colony-stimulating factor- and receptor activator of nuclear factor-κB-dependent osteoclastogenesis and required for efficient bone resorption. Cysteamine had no impact on osteoclastogenesis but inhibited in vitro HD osteoclastic resorption; however, NC OC-mediated bone resorption was impaired only at high doses. Only low concentrations of cysteamine (50 µM) stimulated osteoblastic differentiation and maturation, while this effect was no longer observed at higher concentrations (200 µM). Conclusion: CTNS is required for proper osteoclastic activity. In vitro low doses of cysteamine have beneficial antiresorptive effects on healthy human-derived OCs and may partly correct the CTNS-induced osteoclastic dysfunction in patients with NC. Moreover, in vitro low doses of cysteamine also stimulate osteoblastic differentiation and mineralization, with an inhibitory effect at higher doses, likely explaining, at least partly, the bone toxicity observed in patients receiving high doses of cysteamine.


Assuntos
Reabsorção Óssea/metabolismo , Cistinose/fisiopatologia , Síndrome de Fanconi/complicações , Osteoclastos/patologia , Osteogênese/fisiologia , Animais , Reabsorção Óssea/etiologia , Diferenciação Celular , Células Cultivadas , Cistinose/complicações , Síndrome de Fanconi/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Camundongos , Osteoclastos/metabolismo
16.
Saudi J Kidney Dis Transpl ; 28(5): 1180-1183, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28937083

RESUMO

Cystinosis is an autosomal recessive, lysosomal storage disease characterised by the accumulation of the amino acid cystine in different organs and tissues. It is a multisystemic disease that can present with renal and extra-renal manifestations. In this report, we present the first case of transplanted nephropathic cystinosis in a Tunisian child. A 4-year-old Tunisian boy born to nonconsanguineous parents, was treated in our medical services in 1990 for cystinosis. Since the age of five months, he developed symptoms of severe weight loss, vomiting, dehydration, and polyuria. He manifested the Toni Debré Fanconi syndrome. Slit lamp examination of the anterior segment of both eyes revealed fine, shiny crystal-like deposits diffusely distributed in the corneal epithelium and the stroma. Our patient had renal failure. At the age of seven, he reached terminal chronic renal failure and was treated with peritoneal dialysis. Hemodialysis was started at the age of nine years. At the age of 13 years, he received a renal transplantation and was started on cysteamine 1999, five months after the renal transplantation. Currently, the patient is 28-year-old. The graft has survived 15 years after the transplantation. Renal functions were stable with a serum creatinine of 123 µmol/L at last follow-up.


Assuntos
Cistinose/terapia , Síndrome de Fanconi/terapia , Falência Renal Crônica/terapia , Transplante de Rim , Diálise Renal , Pré-Escolar , Cisteamina/uso terapêutico , Cistinose/complicações , Cistinose/diagnóstico , Progressão da Doença , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/etiologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Masculino , Diálise Peritoneal , Fatores de Tempo , Resultado do Tratamento
17.
Pediatr Int ; 59(11): 1178-1182, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28871612

RESUMO

BACKGROUND: Cystinosis is a rare metabolic genetic disorder caused by a mutation in cystinosin lysosomal cystine transporter (CTNS). The diagnosis of nephropathic cystinosis (NC) is made by observing corneal cystine crystals and/or measuring the cystine content of leukocytes. CTNS mutation analysis confirms the diagnosis of cystinosis, but leukocyte cystine measurement and CTNS analysis have not been widely available, and cystine crystals in the cornea may not be apparent in the first months of life. Cystine crystal deposition can be seen in the bone marrow earlier than corneal deposition, in patients with NC. METHODS: Ten patients with cystinosis diagnosis were enrolled in the study. Medical records were reviewed retrospectively to collect demographic and clinical data such as age at diagnosis, disease presentation, parental consanguinity, family history, corneal cystine deposition, leukocyte cystine level, bone marrow cystine deposition, presence of renal failure, follow-up time and prognosis. RESULTS: Cystine crystals were seen in all of the patients' fresh bone marrow aspiration samples. Eight patients had corneal cystine deposition. Leukocyte cystine measurement could have been performed in four patients who had come from another center. Complications such as pulmonary hypertension and idiopathic intracranial hypertension (IIH) were observed in two patients. CONCLUSIONS: Bone marrow aspiration might be an easy and short-cut diagnostic tool for NC especially when it is not possible to measure fibroblast cystine content. Additionally some rare complications such as pulmonary hypertension and IIH can be encountered during the course of NC.


Assuntos
Medula Óssea/patologia , Cistina/metabolismo , Cistinose/diagnóstico , Criança , Pré-Escolar , Cistinose/complicações , Cistinose/metabolismo , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
18.
Neuromuscul Disord ; 27(9): 873-878, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28629674

RESUMO

Nephropathic cystinosis is an autosomal recessive lysosomal disease in which cystine cannot exit the lysosome to complete its degradation in the cytoplasm, thus accumulating in tissues. Some patients develop a distal myopathy involving mainly hand muscles. Myopathology descriptions from only 5 patients are available in the literature. We present a comprehensive clinical, pathological and genetic description of 3 patients from 2 families with nephropathic cystinosis. Intrafamiliar variability was detected in one family in which one sibling developed a severe distal myopathy while the other sibling did not show any signs of skeletal muscle involvement. One of the patients was on treatment with Cysteamine for over 12 years but still developed the usual complications of nephropathic cystinosis in his twenties. Novel pathological findings consisting in sarcoplasmic deposits reactive for slow myosin were identified. Three previously known and one novel mutation are reported. Nephropathic cystinosis should be included in the differential diagnosis of distal myopathies in those with early renal failure. Novel clinical and pathological features are reported here contributing to the characterization of the muscle involvement in nephropathic cystinosis.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Cistinose , Miopatias Distais , Miosinas Cardíacas/genética , Cistina/metabolismo , Cistinose/complicações , Cistinose/genética , Cistinose/patologia , Miopatias Distais/etiologia , Miopatias Distais/genética , Miopatias Distais/patologia , Saúde da Família , Feminino , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/ultraestrutura , Mutação/genética , Cadeias Pesadas de Miosina/genética , Miosinas/metabolismo , Adulto Jovem
19.
Cardiol Young ; 27(7): 1434-1436, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28490397

RESUMO

Cystinosis is a rare, autosomal-recessive genetic disorder. The kidneys are commonly involved, as there is cystinosin protein malfunction, and nephropathic cystinosis ensues. Although cardiac and vascular involvements are rare, we describe a unique case of aortic dissection in a 25-year-old female with cystinosis. We discuss the possible aetiologies of aortic dissection in this condition.


Assuntos
Aneurisma Dissecante/complicações , Aneurisma Aórtico/complicações , Cistinose/complicações , Adulto , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/cirurgia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/cirurgia , Cistinose/genética , Ecocardiografia , Feminino , Humanos
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