Cistinosis nefropática: caso clínico que ilustra diagnóstico molecular

Abstract

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 4 th 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. (Rev Med Chile 2018; 146: 111-115) L a cistinosis nefropática (CN; OMIM#219800) es una enfermedad autosómica recesiva aso-ciada a variantes patogénicas en el gen CT-NS(MIM#606272), codificante para cistinosina, que funciona como proteína transportadora de cistina en los lisosomas 1,2. Cuando la cistinosina es defectuosa, se acumula cistina que precipita en forma de cristales, lo que conduce a un deterioro progresivo de los órganos afectados. La frecuencia de la CN se estima en 1/100.000-200.000 nacidos vivos y su presentación clínica es de expresión variable, destacando los síntomas derivados de la tubulopatía con el síndrome de Fanconi 3,4. El 95% de los casos de CN se inicia antes de los 6 meses de vida, que constituye la forma más severa, dado que progresa a enfermedad renal crónica (ERC) terminal en la primera década 5. La CN tiene un manejo sintomático de la ERC y del síndrome de Fanconi, sin embargo, actualmente existe un tratamiento específico para reducir los niveles de cistina mediante el uso de cisteamina. Este medicamento fue creado en 1979 y permite la externalización de cisteína para evitar la acumulación intracelular de cistina 6 El uso precoz de cisteamina ha permitido prevenir significativamente la progresión del daño renal y el ingreso a diálisis, mejorando la expectativa de vida de los pacientes. En Chile no existen registros