Fibrosing colonopathy associated with cysteamine bitartrate delayed-release capsules in cystinosis patients.

BACKGROUND: The objective of this report is to identify and characterize cases of fibrosing colonopathy, a rare and underrecognized adverse event, associated with cysteamine delayed-release (DR) in patients with nephropathic cystinosis. METHODS: We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the medical literature for postmarketing reports of fibrosing colonopathy associated with cysteamine through August 2, 2023. RESULTS: We identified four cases of fibrosing colonopathy reported with the use of cysteamine DR. The time to onset ranged from 12 to 31 months. In one case, the patient required surgery to have a resection of a section of the strictured colon and a diverting ileostomy. Fibrosing colonopathy was diagnosed by histopathology in two of the cases. CONCLUSIONS: Our case series identified the risk of fibrosing colonopathy in patients taking cysteamine DR and prompted regulatory action by the FDA. As outlined in changes to the U.S. prescribing information for cysteamine DR, healthcare professionals should be aware of the potential risk of fibrosing colonopathy with cysteamine DR, especially as symptoms can be non-specific leading to misdiagnosis or delayed diagnosis. If the diagnosis of fibrosing colonopathy is confirmed, consideration should be given to permanently discontinuing cysteamine DR and switching to cysteamine immediate-release treatment.

Comparison of Scheimpflug Corneal Tomography and Anterior Segment Optical Coherence Tomography Measurements in Corneal Cystinosis: A Case Series.

PURPOSE: To report the clinical course and compare the utility of Scheimpflug tomography (ST) and anterior segment optical coherence tomography (AS-OCT) for central corneal thickness (CCT) and corneal densitometry (CD) assessment in patients with corneal crystals owing to nephropathic cystinosis. METHODS: A retrospective chart analysis of three patients with nephropathic cystinosis and the presence of corneal cystine crystals in both eyes was performed. All patients underwent clinical examination and anterior segment photography, ST, and AS-OCT scans. Corneal densitometry was exported from built-in proprietary software for ST and from custom-made validated software for AS-OCT. Anterior segment optical coherence tomography images were rescaled to grayscale units from 0 (maximum transparency) to 100 (minimum transparency) to match built-in ST densitometry readings. Furthermore, the mean pixel intensity, representative of CD, was calculated from the pixels corresponding to the segmented cornea. RESULTS: All three patients had pathognomonic cystine crystals deposits in the cornea and were treated with cysteamine medications that resulted in clinical improvement. The CCT measured using ST exhibited a range from 560 to 958 µm. Conversely, when assessed with AS-OCT, the CCT varied within the range of 548 to 610 µm. Both examinations could be performed, but in the more severe cases, AS-OCT showed far greater utility to estimate CD. In four of six eyes examined, ST showed disproportionate CCT values, compared with the AS-OCT, whereas reliable CD measurements were only available in AS-OCT. CONCLUSION: The AS-OCT could be considered a baseline ocular measurement in cystinosis and in the evaluation of disease progression and treatment efficacy.

Renal transplantation for infantile and juvenile cystinosis: Two case report and review of the literature.

Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by cystine buildup in various tissues, including the kidneys. Renal involvement is the primary manifestation, leading to end-stage renal disease (ESRD) if left untreated. Kidney transplantation (KT) in patients with cystinosis has significantly improved their prognosis for the disease outcome. Detailed reports on preoperative and Long-term postoperative management in these patients remain sparse. This report discusses the outcomes of two young adult patients of Middle Eastern descent with cystinosis who underwent KT. The first patient, diagnosed with infantile nephropathic cystinosis treated by cystine-depleting therapy, was operated by KT at the age of 18. The second patient, diagnosed with juvenile cystinosis, underwent transplantation at the age of 35 after being treated with hemodialysis. Our report describes detailed pre- and postoperative managements, including laboratory results, and pharmacological interventions. Both cases highlighted the varying clinical manifestations and disease severity between infantile and juvenile cystinosis. Pre-transplant conditions included renal dysfunction, growth retardation, secondary hyperparathyroidism, anemia, and extrarenal manifestations. Following KT, both patients experienced regained renal function, resolution of extrarenal complications, and normalization of laboratory parameters. Furthermore, both patients showed excellent postoperative outcomes with no acute rejection or allograft-related complications. KT is the treatment of choice for cystinosis patients with ESRD. Long-term follow-up post-transplantation is crucial to maintain good graft function. Further studies may elucidate optimal pre- and postoperative management protocols for this rare condition.

Multidisciplinary approach for patients with nephropathic cystinosis: model for care in a rare and chronic renal disease / Abordagem multidisciplinar para pacientes com cistinose nefropática: modelo para atendimento em uma doença renal rara e crônica

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.

Cristales oportunos: cistinosis nefropática. Reporte de caso / Timely cristals: nephropathic cystinosis. Case report

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.

Cistinosis nefropática: caso clínico que ilustra diagnóstico molecular / Nephropatic cystinosis: report of one case

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.

Cistinosis nefropática infantil / Nephropathic cystinosis in children

La cistinosis nefropática, rara afección recesiva, se produce por defecto en el transporte lisosomal de cistina, y depósitos de cristales intracelulares en riñón, córnea, y otros tejidos. Constituye la primera causa congénita de síndrome de Fanconi, y evoluciona en la primera década de la vida a insuficiencia renal crónica. El diagnóstico se confirma por una detección de cistina en leucocitos y linfoblastos circulantes. Su tratamiento consiste en la reposición de las pérdidas por la tubolopatía, administración de cisteamina, que depleta cistina y favorece su transporte por la pared lisosomal. El objetivo de la presentación es dar a conocer el primer caso de cistinosis documentado y tratado en Chile. Se presenta el caso de un menor hospitalizado a los quince meses de vida, con desnutrición avanzada, raquitismo clínico, deshidratación severa, acidosis metabólica, hipokalemia e hipofosfemia severas, comprobándose tubulopatía de Fanconi. Se detectó concentración elevada de cistina en polimorfonucleares, confirmando diagnóstico de cistinosis. En tratamiento desde hace dos años con cisteamina oral, muestra excelente evolución pondoestatural y conservación de la función renal, persistiendo la tubulopatía

Cistinose nefropática: relato de 2 casos e revisäo da literatura / Nephropathic cystinosis: report of two cases and review of the literature

Os autores descrevem dois casos de cistinose nefropática, da forma infantil, que se apresentaram com síndrome de Fanconi e diabetes insipidus nefrogênico. Após a confirmaçäo diagnóstica através da identificaçäo de cristais de cistina pelo exame de lâmpada de fenda e aspirado de medula óssea, os pacientes receberam tratamento convencional de reposiçäo das perdas renais de eletrólitos e minerais. O paciente 1 evoluiu para óbito após quadro de broncopneumonia. No paciente 2 foi iniciado tratamento com cisteamina, que é eficaz na depleçäo de cistina dos tecidos, na dose média de 50 mg/kg/dia, sendo este o primeiro caso de terapêutica com cisteamina em nosso meio.

Cistinosis: informe de un caso / Cystinosis: a case report

Se presenta el caso de un niño de dos años de edad cistinosis clásica, manifestada por síndrome de Fanconi (glucosuria, aminoaciduria y fosfaturia), raquitismo, talla baja, presencia de cristales de cistina en córnea y daño glomerular progresivo; demostrándose en le biopsia renal por medio de microscopia electrónica el acúmulo de los característicos cristales hexagonales de cistina. Debido a que la frecuencia de esta patología en nuestro país es muy baja, y el cuadro clínico de nuestro paciente es representativo de la variante infantil nefropática, decidimos realizar este informe