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1.
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
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.
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
5.
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
6.
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
7.
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
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.
Indian J Ophthalmol ; 67(1): 153-155, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30574930

RESUMO

A 36-year-old female presented initially with photophobia and visual deterioration. After examination and laboratory tests, patient was diagnosed with cystinosis. Cysteamine drops 4 × 1 drops/day was given as treatment for 1 year. During follow-up, in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) was performed. Photophobia was relieved and IVCM obtained the decrease in size and density of corneal crystals 1 year after. Depth of corneal crystals did not change but crystal density score reduced with cysteamine treatment.


Assuntos
Segmento Anterior do Olho/diagnóstico por imagem , Córnea/patologia , Doenças da Córnea/diagnóstico , Cisteamina/administração & dosagem , Cistinose/tratamento farmacológico , Microscopia Confocal/métodos , Tomografia de Coerência Óptica/métodos , Adulto , Doenças da Córnea/tratamento farmacológico , Cristalização , Eliminadores de Cistina/administração & dosagem , Cistinose/diagnóstico , Feminino , Seguimentos , Humanos , Soluções Oftálmicas , Acuidade Visual
12.
Rev Med Chil ; 146(1): 111-115, 2018 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-29806685

RESUMO

Nephropatic cystinosis (NC) is a rare disease associated with pathogenic variants in the CTNS gene, with a common variant that consists of a 57kb-deletion involving CTNS. Patients with NC that are treated with cysteamine improve their life quality and expectancy. We report a 12-month-old girl with a poor growth rate since the 4th month of life. She was admitted to the Hospital with acute kidney injury, severe dehydration and metabolic acidosis. She was treated with volume restorative and bicarbonate. Proximal tubulopathy and Fanconi's syndrome was diagnosed. Medical treatment improved renal function that was stabilized in stage 4 chronic kidney disease (CKD). Since infantile NC was suspected, CTNS genetic analysis was considered. Genomic DNA was isolated from peripheral blood to perform PCR for exons 3-12 in CTNS gene and for the specific 57kb-deletion PCR. Afterwards, variant segregation analysis was performed in the familiar trio. The genetic analysis showed that the patient was homozygous for the common 57kb-deletion encompassing CTNS that had been inherited from her asymptomatic heterozygous parents. The molecular confirmation allowed genetic counselling for parents and facilitated the access to cysteamine. Oral treatment with cysteamine resulted in improvement of renal function to CKD stage 3. After 16 months of treatment the patient shows metabolic stability and mild recovery of height. Ophthalmologic follow-up detected ocular cystine crystals 12 months after diagnosis, starting cysteamine drops.


Assuntos
Cistinose/diagnóstico , Cistinose/genética , Cisteamina/uso terapêutico , Eliminadores de Cistina/uso terapêutico , Cistinose/tratamento farmacológico , Feminino , Humanos , Lactente , Reação em Cadeia da Polimerase , Diagnóstico Pré-Natal
13.
Internist (Berl) ; 59(8): 861-867, 2018 08.
Artigo em Alemão | MEDLINE | ID: mdl-29671012

RESUMO

This article presents a case of cystinosis in a young man. Diagnosis of the disease and the problem of transition to adult care are described. Cystinosis is a rare lysosomal storage disease with first manifestation in early childhood presenting as renal Fanconi syndrome. Without treatment, the disease leads to severe health impairment. Due to the rarity of the disease, a correct diagnosis is often delayed. Without treatment, cystinosis often leads to end-stage renal failure, blindness, hypothyroidism, diabetes mellitus, and rickets. Cystine-depleting therapy with cysteamine significantly improves mortality and quality of life.


Assuntos
Cisteamina/uso terapêutico , Eliminadores de Cistina/uso terapêutico , Cistina/sangue , Cistina/metabolismo , Cistinose/diagnóstico , Cistinose/tratamento farmacológico , Síndrome de Fanconi/tratamento farmacológico , Adulto , Criança , Pré-Escolar , Cisteamina/administração & dosagem , Eliminadores de Cistina/administração & dosagem , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/etiologia , Humanos , Rim/patologia , Lisossomos/metabolismo , Masculino , Qualidade de Vida
15.
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
16.
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
18.
BMC Nephrol ; 18(1): 300, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28950840

RESUMO

BACKGROUND: Cystinosis is a rare autosomal recessive lysosomal disorder characterized by the accumulation of cystine in lysosomes. Cystinosis is much rarer in Asian than Caucasian populations. There are only 14 patients have with cystinosis alive in Japan. Most cystinosis is the nephropathic infantile form, as indicated by its apparent and severe clinical manifestations, including renal and ocular symptoms. Patients with the nephropathic juvenile form account for 5% of those with cystinosis. Their diagnosis is frequently delayed and difficult because of slower progression to end-stage renal disease and fewer cystine crystals in the cornea. Molecular analysis and a cysteine-binding protein assay should be performed when patients with proximal tubulopathy of an unknown origin are encountered. CASE PRESENTATION: A 12-year-old boy had been suffering from Fanconi syndrome since he was 3 years old. He was only recently diagnosed despite repeated ophthalmological examinations. Corneal cystine crystals were found when he was 12 years old, and he was diagnosed with cystinosis by high free cystine content in granulocytes (6.36 nmol half-cystine/mg protein, normal: <0.15). Analysis of the CTNS gene showed two novel heterozygous single nucleotide substitutions of c.329G > C and c.329 + 2 T > C. Both were splicing site variants causing exon 6 skipping proven by transcript analysis, although the functional prediction site showed c.329G > C, p.(Gly110Ala) as a benign missense substitution. The patient's estimated glomerular filtration rate was 66.8 mL/min/1.73 m2. He was immediately treated with cysteamine after diagnosis. CONCLUSIONS: Even if no ophthalmological abnormalities are present, nephropathic juvenile cystinosis should be suspected in children with Fanconi syndrome. Transcript analysis was useful to detect pathogenic splicing variants in this patient.


Assuntos
Cistinose/diagnóstico , Cistinose/genética , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/genética , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Criança , Cisteamina/uso terapêutico , Cistinose/tratamento farmacológico , Síndrome de Fanconi/tratamento farmacológico , Humanos , Masculino , Síndrome Nefrótica/tratamento farmacológico , Microscopia com Lâmpada de Fenda/métodos
19.
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
20.
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
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