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1.
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
2.
Nephron ; 141(2): 133-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30554218

RESUMO

Mutations in the CTNS gene encoding the lysosomal membrane cystine transporter cystinosin are the cause of cystinosis, an autosomal recessive lysosomal storage disease. More than 140 CTNS mutations have been reported worldwide. Recent studies have discovered that cystinosin exerts other key cellular functions beyond cystine transport such as regulation of oxidative state, lysosomal dynamics and autophagy. Here, we review the different mutations described in the CTNS gene and the geographical distribution of incidence. In addition, the characteristics of the various mutations in relation to the functions of cystinosin needs to be further elucidated. In this review, we highlight the functional consequences of the different mutations in correlation with the clinical phenotypes. Moreover, we propose how this understanding would be fundamental for the development of new technologies through targeted gene therapy, holding promises for a possible cure of the kidney and extra-renal phenotypes of cystinosis.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Cistinose/genética , Reparo do DNA , Mutação , Animais , Cistinose/epidemiologia , Modelos Animais de Doenças , Genótipo , Geografia , Humanos , Incidência , Fenótipo
3.
Rev. Soc. Colomb. Oftalmol ; 51(1): 86-91, 2018. ilus.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-912665

RESUMO

Objetivo: Describir el caso clínico de un paciente con Cistinosis Nefropática diagnosticado a muy temprana edad. Método: Reporte de caso. Resultados: Se reporta el caso de una paciente de 7 meses de edad, quien consulta con poliuria, piolidipsia, glucosuria y bajo peso para la edad. De acuerdo a protocolos de evaluación interdisciplinaria establecidos con el servicio de Pediatría se logra evidenciar hallazgos oculares que orientan al diagnóstico final de la paciente. Conclusión: La Cistinosis es una enfermedad rara, cursa con manifestaciones oculares que podrían orientar un diagnóstico temprano e incluso predecir la severidad de la enfermedad y brindar la posibilidad de un tratamiento temprano. Es importante establecer protocolos interdisciplinarios, de apoyo diagnóstico, ante la sospecha de enfermedades sistémicas con posible compromiso ocular, en lugar de desistir ante la dificultad para valorar a los niños en la consulta de oftalmología, sobre todo en aquellos menores de un año. Se demuestra este caso con fines académicos teniendo en cuenta la baja incidencia de la enfermedad, pero también para destacar la importancia de contar con protocolos de atención interdisciplinaria ante la sospecha de enfermedades metabólicas en todas las edades.


Purpose: To describe a case of an infant with Nephropathic Cystinosis and the ocular fi ndings that leads to the diagnosis. Method: Case report. Results: Th is report describe a prompt and accurate diagnosis of a 7 months old patient, who consults with polyuria, piolidipsia, glucosuria and low weight. According to interdisciplinary evaluation protocols previusly established with Pediatrics services, it was possible to demonstrate ocular fi ndings of the disease, guiding the physician to the fi nal diagnosis. Conclusion: Cystinosis is a rare disease, its clinical presentation has ocular manifestations that could guide diagnosis and even predict its severity, off ering the possibility of an early treatment. When one suspect a systemic disease, It is important to establish interdisciplinary protocol, instead of surrendering to the challenge of an ophthalmological examination of an infant. We choose this case due to its low incidence, but also to highlight the importance of having interdisciplinary care protocols when a metabolic disease is suspected.


Assuntos
Cistinose/epidemiologia , Cistinose/diagnóstico , Oftalmopatias
4.
BMC Nephrol ; 18(1): 210, 2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-28673276

RESUMO

BACKGROUND: Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess the management characteristics in DiN compared with developed nations [DeN]. METHODS: A questionnaire was sent between April 2010 and May 2011 to 87 members of the International Pediatric Nephrology Association, in 50 countries. RESULTS: A total of 213 patients were included from 41 centres in 30 nations (109 from 17 DiN and 104 from 13 DeN). 7% of DiN patients died at a median age of 5 years whereas no death was observed in DeN. DiN patients were older at the time of diagnosis. In DiN, leukocyte cystine measurement was only available in selected cases for diagnosis but never for continuous monitoring. More patients had reached end-stage renal disease in DiN (53.2 vs. 37.9%, p = 0.03), within a shorter time of evolution (8 vs. 10 yrs., p = 0.0008). The earlier the cysteamine treatment, the better the renal outcome, since the median renal survival increased up to 16.1 [12.5-/] yrs. in patients from DeN treated before the age of 2.5 years of age (p = 0.0001). However, the renal survival was not statistically different between DeN and DiN when patients initiated cysteamine after 2.5 years of age. The number of transplantations and the time from onset of ESRD to transplantation were not different in DeN and DiN. More patients were kept under maintenance dialysis in DiN (26% vs.19%, p = 0.02); 79% of patients from DiN vs. 45% in DeN underwent peritoneal dialysis. CONCLUSIONS: Major discrepancies between DiN and DeN in the management of nephropathic cystinosis remain a current concern for many patients living in countries with limited financial resources.


Assuntos
Cistinose/epidemiologia , Saúde Global , Internacionalidade , Falência Renal Crônica/epidemiologia , Médicos , Inquéritos e Questionários , Adolescente , Adulto , Criança , Pré-Escolar , Cistinose/diagnóstico , Cistinose/terapia , Países em Desenvolvimento , Feminino , Seguimentos , Humanos , Lactente , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Masculino , Estudos Retrospectivos , Adulto Jovem
5.
J Pediatr Endocrinol Metab ; 29(8): 965-9, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27269891

RESUMO

BACKGROUND: This study was conducted to investigate CTNS (cystinosin, lysosomal cystine transporter) gene mutations and the clinical spectrum of nephropathic cystinosis among patients diagnosed with the disease in a single center in Turkey. METHODS: Patients' clinical and laboratory data were extracted from an electronic health registry. Molecular CTNS gene analysis was performed using either next-generation sequencing or Sanger sequencing. RESULTS: Eleven patients (age range: 1.5-12 years) from nine families were identified. The presenting complaint was growth retardation in seven patients; polydipsia and polyuria in three patients; and vomiting in two patients. At presentation, electrolyte loss was noted in all patients, of which eight patients presented with metabolic acidosis, and three patients presented with metabolic alkalosis. All patients also presented with proteinuria and glucosuria, and four patients developed varying degrees of renal insufficiency, for which peritoneal dialysis was initiated in one patient. Cystine crystals were detected via ocular examination in one patient at presentation. No cystine crystals were detected among patients who underwent bone marrow aspiration. In the CTNS gene, a p.T7FX7 (c.18-21del4bp) mutation was detected in three patients, whereas a p.E227E (c.681 G>A) (homozygous) mutation was detected in eight patients. CONCLUSIONS: We detected two distinct mutations, p.T7FX7 (c.18-21del4bp) and p.E227E (c.681 G>A) (homozygous), in the CTNS gene in 11 patients with cystinosis from the East Anatolian region of Turkey. Patients with a homozygous c.681 G>A (p.E227E) mutation are more likely to develop chronic renal failure and should be monitored closely, whereas patients with a p.T7FX7 (c.18-21del4bp) mutation have a milder phenotype. Additionally, metabolic alkalosis does not exclude cystinosis, although cystinosis is a cause of proximal renal tubular acidosis.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Biomarcadores/metabolismo , Cistinose/genética , Mutação/genética , Criança , Pré-Escolar , Cistinose/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Turquia/epidemiologia
6.
Nefrologia ; 35(6): 547-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26565940

RESUMO

OBJECTIVE: Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin protein. The aim of this study was to sequence the coding exons of the CTNS gene in five different Jordanian families and one family from Sudan with nephropathic cystinosis. METHODS: Probands initially presented with Fanconi syndrome symptoms. An eye examination showed the accumulation of cystine crystals in the cornea by the age of 2 years, suggesting cystinosis. All of the coding exons and flanking intronic sequences and the promoter region of the CTNS gene were amplified using polymerase chain reaction and subjected to sequencing. RESULTS: None of the probands in this study carried the European 57-kb deletion in the CTNS gene. Seven variants in the coding and promoter sequence of the CTNS gene were identified in the probands of this study. Two of these variants were a CTNS mutation that was previously identified in a heterozygous genotype in two different patients of European descendant. The two mutations were c.829dupA in exon 10 and c.890G>A in exon 11. The proband of family 2 was compound-heterozygous for the two mutations. CONCLUSION: This study is the first molecular study of infantile nephropathic cystinosis in Jordan. We successfully identified the causative CTNS mutations in Jordanian families. The results provide a basis for the early detection of the disease using molecular tools in a highly consanguineous Jordanian population.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Cistinose/genética , Adulto , Alelos , Criança , Pré-Escolar , Consanguinidade , Cistinose/epidemiologia , Cistinose/etnologia , Análise Mutacional de DNA , Éxons/genética , Feminino , Mutação da Fase de Leitura , Duplicação Gênica , Genótipo , Humanos , Lactente , Jordânia/epidemiologia , Masculino , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Sudão/etnologia
7.
Nefrología (Madr.) ; 35(3): 304-321, mayo-jun. 2015. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-140060

RESUMO

Introduction: Cystinosis is a rare lysosomal systemic disease that mainly affects the kidney and the eye. Patients with cystinosis begin renal replacement therapy during the first decade of life in absence of treatment. Prognosis of cystinosis depends on early diagnosis, and prompt starting and good compliance with cysteamine treatment. Kidney disease progression, extra-renal complications and shorter life expectancy are more pronounced in those patients that do not follow treatment. The objective of this work was to elaborate recommendations for the comprehensive care of cystinosis and the facilitation of patient transition from paediatric to adult treatment, based on clinical experience. The goal is to reduce the impact of the disease, and to improve patient quality of life and prognosis. Methods: Bibliographic research and consensus meetings among a multidisciplinary professional team of experts in the clinical practice, with cystinotic patients (T-CiS.bcn group) from 5 hospitals located in Barcelona. Results: This document gathers specific recommendations for diagnosis, treatment and multidisciplinary follow-up of cystinotic patients in the following areas: nephrology, dialysis, renal transplant, ophthalmology, endocrinology, neurology, laboratory, genetic counselling, nursing and pharmacy. Conclusions: A reference document for the comprehensive care of cystinosis represents a support tool for health professionals who take care of these patients. It is based on the following main pillars: (a) a multi-disciplinary approach, (b) appropriate disease monitoring and control of intracellular cystine levels in leukocytes, (c) the importance of adherence to treatment with cysteamine, and (d) the promotion of patient self-care by means of disease education programmes. All these recommendations will lead us, in a second phase, to create a coordinated transition model between paediatric and adult care services which will contemplate the specific needs of cystinosis (AU)


Introducción: La cistinosis es una enfermedad lisosomal minoritaria de expresión sistémica con especial afectación renal y oftalmológica, en la que los pacientes inician terapia renal sustitutiva en la primera década de la vida en ausencia de tratamiento. El pronóstico de la cistinosis depende del diagnóstico precoz, la pronta instauración del tratamiento con cisteamina y el buen cumplimiento terapéutico. La progresión de la enfermedad renal y de las complicaciones extrarrenales y una menor supervivencia, son más acentuadas en pacientes no adherentes. Objetivo: El objetivo de este trabajo fue la elaboración de unas recomendaciones para la atención integral de la cistinosis y la transición del adolescente a la medicina del adulto, basadas en la experiencia clínica, con el fin de reducir el impacto de la enfermedad y mejorar la calidad de vida y el pronóstico del paciente. Método: Búsqueda bibliográfica y reuniones de consenso de un equipo multidisciplinar de expertos en la práctica clínica con pacientes afectos de cistinosis (Grupo T-CiS.bcn), procedentes de 5 hospitales localizados en Barcelona. Resultados: El documento recoge recomendaciones específicas y necesarias para el diagnóstico, tratamiento y seguimiento multidisciplinar de la cistinosis en las siguientes áreas: nefrología, diálisis, trasplante renal, oftalmología, endocrinología, neurología, laboratorio, consejo genético, enfermería y farmacia. Conclusiones: Disponer de un documento de referencia para la atención integral de la cistinosis constituye una herramienta de soporte para los profesionales de la salud que asisten a estos pacientes. Los principales pilares en los que se sustenta son: a) el enfoque multidisciplinar, b) la adecuada monitorización de la enfermedad y control de los niveles de cistina intraleucocitarios, c) la importancia de la adherencia al tratamiento con cisteamina y d) la promoción del autocuidado del paciente mediante programas de educación en la enfermedad. Todo ello conducirá, en una segunda fase, a la elaboración de un modelo de transición coordinado entre los servicios de pediatría y de adultos que contemple las necesidades específicas de la cistinosis (AU)


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Cistinose/epidemiologia , Cistinose/prevenção & controle , /métodos , /tendências , Cisteamina/administração & dosagem , Cisteamina/análise , Prognóstico , Diagnóstico Precoce , Síndrome de Fanconi/complicações , Síndrome de Fanconi/diagnóstico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etiologia , Diálise Renal/métodos , Diálise Renal , Biologia Molecular/métodos
12.
Pediatr Nephrol ; 27(1): 115-21, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21786142

RESUMO

We report the molecular findings for the CTNS gene in 12 Turkish cystinosis patients aged 7-29 years. All presented initially with severe failure to thrive, polyuria, and polydipsia. Cystinosis was diagnosed at age 1 month to 9 years. Seven patients reached end-stage renal failure at ages ranging from 6.5 to 15 years. Whereas three of the remaining five have renal Fanconi syndrome with proteinuria, two have had kidney failure of varying degrees. Molecular analyses involved an initial multiplex polymerase chain reaction (PCR) to determine the presence or absence of the 57-kb northern European founder deletion in CTNS, followed by sequencing of the ten coding exons of CTNS. Comprehensive mutation analysis verified that none of the 12 patients carried the common 57-kb deletion. We identified four previously reported nucleotide variations associated with cystinosis and five new variants: a 10-kb deletion, three missense variants, and a nucleotide substitution in a potential branch point site of intron 4. This study is the first molecular analysis of Turkish cystinosis patients and provides guidance for the molecular diagnosis of cystinosis in this population.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Cistinose/genética , Mutação , Adolescente , Adulto , Criança , Cistinose/complicações , Cistinose/epidemiologia , Análise Mutacional de DNA , Progressão da Doença , Éxons , Insuficiência de Crescimento/genética , Síndrome de Fanconi/genética , Feminino , Predisposição Genética para Doença , Humanos , Íntrons , Falência Renal Crônica/genética , Masculino , Mutação de Sentido Incorreto , Fenótipo , Mutação Puntual , Polidipsia/genética , Reação em Cadeia da Polimerase , Poliúria/genética , Proteinúria/genética , Insuficiência Renal/genética , Deleção de Sequência , Turquia/epidemiologia , Adulto Jovem
13.
J Inherit Metab Dis ; 33(6): 787-93, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20814825

RESUMO

INTRODUCTION: Cystinosis is an autosomal recessive disorder leading to intralysosomal cystine accumulation in various tissues. It causes renal Fanconi syndrome and end stage renal failure around the age of 10 years if not treated with cysteamine. Children with cystinosis seem to have a normal intelligence but frequently show learning difficulties. These problems may be due to specific neurocognitive deficits rather than impaired renal function. Whether cysteamine treatment can improve cognitive functioning of cystinosis patients is thus far unknown. We aim to analyze neurocognitive functioning of school-aged cystinosis patients treated with cysteamine in order to identify specific deficits that can lead to learning difficulties. PATIENTS AND METHODS: Fourteen Dutch and Belgian school-aged cystinosis patients were included. Glomerular filtration rate was estimated using the Schwartz formula. Children were tested for general intelligence, visual-motor integration, inhibition, interference, sustained attention, accuracy, planning, visual memory, processing speed, motor planning, fluency and speed, and behavioural and emotional functioning using standardized methods. RESULTS: Glomerular filtration rate ranged from 22 to 120 ml min(-1) 1.73 m(-2). Median full-scale intelligence was below the average of a normal population (87, range 60-132), with a discrepancy between verbal (median 95, range 60-125) and performance (median 87, range 65-130) intelligence. Over 50% of the patients scored poorly on visual-motor integration, sustained attention, visual memory, planning, or motor speed. The other tested areas showed no differences between patients' and normal values. CONCLUSION: Neurocognitive diagnostics are indicated in cystinosis patients. Early recognition of specific deficits and supervision from special education services might reduce learning difficulties and improve school careers.


Assuntos
Cognição/fisiologia , Cistinose/fisiopatologia , Cistinose/psicologia , Adolescente , Bélgica , Criança , Comportamento Infantil/fisiologia , Cistinose/epidemiologia , Emoções/fisiologia , Feminino , Humanos , Testes de Inteligência , Masculino , Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Países Baixos , População
14.
Nephron Clin Pract ; 114(1): c12-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19816039

RESUMO

INTRODUCTION: The Brazilian Multicenter Nephropathic Study Group, founded in 1999, is currently composed of 16 pediatric nephrology units, which are coordinated by the Pediatric Nephrology Unit of Instituto da Criança--HCFMUSP. This Study Group intends to better know our patients, their special characteristics and facilitates the treatment. OBJECTIVE: To present an update on the demographics of the ongoing study participants with interest on renal function status, response to therapy, and extra-renal complications. METHODS: Patient recruitment to the study is based on informed consent and has been supported by the Brazilian Society of Nephrology, by the creation of an electronic homepage and by the participation in medical meetings and publications in medical periodicals. Our study protocol involves the initial and follow-up questionnaire, the measurement of intraleukocyte cystine content, initiation and follow-up therapy with cysteamine, and clinical patient follow-up based on a protocol of subsidiary exams. RESULTS: We identified 102 patients (42 females) with nephropathic cystinosis in Brazil since 1999. Forty-six children are followed at the Instituto da Criança/SP, 15 at the Hospital Pequeno Príncipe/PR, 12 at the UNICAMP/SP, 10 at the Unidade de Transplante Renal - HCFMUSP/SP and 3 at the Santa Casa/SP; the remaining patients are followed at the Instituto da Criança and at their respective doctors' offices in different nephrology services in Brazil. Of these patients, 23/102 (22.5%) have normal renal function, 19/102 (18.6%) are in chronic renal failure with conservative treatment, 26/102 are on dialysis (18 on peritoneal dialysis and 8 on hemodialysis), and 34/102 received a renal transplant. The extra-renal involvement diagnosed was: hypothyroidism in 63 patients, diabetes mellitus in 8 patients, muscular involvement in 7 patients, a compromised central nervous system in 5 patients, hepatic complications in 5 patients, and deglutition dysfunction in 2 patients. During this period, 10/102 patients died. Cysteamine has been used by 81/102 patients (20 children started the therapy under 2 years of age). Growth parameters were improved by cysteamine, mainly in the youngest patients. We used recombinant growth hormone in 15 patients with persistent low growth velocity and stature z score under 2.5%. We could also observe a delay in appearance of extra-renal complications in patients receiving cysteamine. CONCLUSION: Our study demonstrates the importance of a multi-center study for recruitment, diagnosis and management of rare diseases. This study promotes access to the adequate treatment with profound impact on the quality of life.


Assuntos
Cistinose/epidemiologia , Nefropatias/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Comorbidade , Cisteamina/administração & dosagem , Cisteamina/uso terapêutico , Cistinose/tratamento farmacológico , Feminino , Taxa de Filtração Glomerular , Humanos , Hipotireoidismo/epidemiologia , Lactente , Nefropatias/tratamento farmacológico , Leucócitos/química , Masculino , Adulto Jovem
15.
J Pediatr ; 151(2): 192-6, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17643777

RESUMO

OBJECTIVES: Infantile nephropathic cystinosis is associated with a specific cognitive deficit in visual spatial processing in older children and adults. The cause of this deficit is unknown. This study was designed to determine whether the cognitive deficit is present in young children with cystinosis, suggesting an early effect of the genetic disorder on brain development. STUDY DESIGN: Young children (n = 25; age, 3-8 years) with cystinosis and 25 matched control subjects underwent cognitive testing, including tests of intelligence, visual perceptual, visual spatial, and visual motor functions. RESULTS: Children with cystinosis performed significantly more poorly on tests of visual spatial and visual motor function than did control subjects. Visual perceptual abilities were equivalent in the 2 groups. CONCLUSION: The same pattern of visual spatial deficit is present in young children with cystinosis as has previously been demonstrated in older children and adults, which suggests that there may be an influence of the cystinosis gene on brain development, rather than an adverse effect of prolonged cystine accumulation in the brain during childhood.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Transtornos Cognitivos/genética , Cistinose/genética , Regulação da Expressão Gênica no Desenvolvimento , Transtornos da Percepção/genética , Distribuição por Idade , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Comorbidade , Cistinose/diagnóstico , Cistinose/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Testes de Inteligência , Masculino , Análise Multivariada , Testes Neuropsicológicos , Transtornos da Percepção/diagnóstico , Transtornos da Percepção/epidemiologia , Probabilidade , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Fatores de Tempo , Percepção Visual/fisiologia
16.
Pediatr Nephrol ; 18(4): 384-90, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12700967

RESUMO

Many of the end-organ effects of cystinosis are known to be risk factors for osteopenia; these include deposition of cystine crystals in bone, hypothyroidism, diabetes mellitus, primary hypogonadism, urinary phosphate wasting, and chronic renal failure. While transplantation may correct the latter, it exposes the child to other risk factors for diminished bone mass, notably the use of high-dose glucocorticoids. Our objective was to determine if these multiple risk factors translate into an increased occurrence of osteopenia, as measured by dual-energy X-ray absorptiometry (DEXA), and/or fractures in this population. We examined the charts, X-rays, and bone mineral density (BMD) of all cystinotic patients post renal transplant for whom this information was available. Lumbar spine BMD was measured by DEXA scan (Hologic 4500). Z-scores were corrected for growth parameters using previously published reference data. Fracture history and pertinent serum markers of bone metabolism were also analyzed. Of the 63 renal transplants performed at our institution, 11 children were transplanted due to cystinosis. Nine of these patients, 5 male and 4 female, had had BMD evaluations, with an average age of 14.3 years (range 5-17 years) at the time of initial BMD post transplant. The mean interval between transplant and BMD evaluation was 39 months (range 3-90 months). Surprisingly, 7 of 9 patients had normal uncorrected BMD values (z-scores -1.92 to +0.02) and 7 of 9 patients had normal corrected values (z-scores -1.20 to +1.93). Three patients suffered from a total of eight fractures. Of the 3 fracture patients, 2 had normal BMD. All patients maintained good graft function and had normal calcium/phosphate mineral status. Of note, 3 of 5 male patients had evidence of primary testicular failure at earlier ages than often described, and this may be an unrecognized risk factor for bone disease in this population. Despite the numerous risk factors for developing osteopenia, these results suggest that the majority of cystinotic patients post renal transplant do not experience reduced bone mineral content as measured by DEXA. However, the significant fracture history among these patients demonstrates that DEXA cannot be used to assess fracture risk in patients with nephropathic cystinosis.


Assuntos
Doenças Ósseas Metabólicas/epidemiologia , Cistinose/epidemiologia , Fraturas Ósseas/epidemiologia , Transplante de Rim , Absorciometria de Fóton , Adolescente , Biomarcadores , Densidade Óssea , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/etiologia , Criança , Cistinose/diagnóstico por imagem , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/etiologia , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Valor Preditivo dos Testes , Fatores de Risco
18.
J Am Soc Nephrol ; 12(10): 2170-4, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11562417

RESUMO

Cystinosis is an autosomal recessive disorder, characterized by an accumulation of intralysosomal cystine, with an incidence of 1 in 100,000 to 200,000 live births. A higher incidence of cystinosis, 1 in 26,000 live births, has been reported in the western French province of Brittany. PCR amplification and sequencing has identified a 27-bp deletion starting 3 bp before the end of exon 8 and continuing into intron 8, 898-900+24del27, which has only been detected in families from this region. Reverse transcription-PCR amplification of RNA from an affected individual has shown that this mutation is indeed a splice-site mutation and results in the production of aberrant transcripts. These transcripts are predicted to either severely truncate cystinosin or alter its topology, thus accounting for the severe phenotype of these individuals. The mutation 898-900+24del27 has been identified in 7 of 18 alleles studied. This mutation is likely to be a founder mutation and would account for the higher incidence of cystinosis in Brittany.(1)


Assuntos
Cistinose/epidemiologia , Cistinose/genética , Efeito Fundador , Mutação , Adolescente , Adulto , Sequência de Bases/genética , Criança , França/epidemiologia , Deleção de Genes , Humanos , Incidência , Dados de Sequência Molecular , RNA/genética , Processamento de RNA
20.
J Inherit Metab Dis ; 8(1): 2-4, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-3921756

RESUMO

In our survey, 101 infants and children with cystinosis were registered in the Federal Republic of Germany. Ninety-five patients showed the infantile type of cystinosis, five the adolescent type and one possibly the adult type. The minimum incidence rate of infantile and adolescent cystinosis in the FRG was 1 patient per 179 000 live-births. In contrast to other countries, cystinotic patients were evenly distributed in the FRG. Patients with cystinosis originated more frequently from rural communities than from large cities. Before 1968 most patients died before reaching terminal renal failure, usually due to uncontrolled disturbances of water and electrolyte metabolism. Since 1976 the causes of death other than uraemia have been rare and most patients with terminal renal failure have entered a renal replacement program.


Assuntos
Cistinose/epidemiologia , Adolescente , Criança , Pré-Escolar , Cistinose/complicações , Cistinose/genética , Feminino , Alemanha Ocidental , Humanos , Lactente , Falência Renal Crônica/etiologia , Masculino , Sistema de Registros , Estatística como Assunto
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