CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Mutation in SGPL1, Causing Sphingosine-1- Phosphate Lyase Deficiency, Leads to a Novel Form of Primary Adrenal Insufficiency with Steroid Resistant Nephrotic Syndrome
Autor/es:
PRASAD, R.; PIANTANIDA, J.J.; METHERELL, L.; BRASLAVSKY, D.; CASSINELLI, H.; WAINBERG, E.; BARBAGELATA, E.; BERGADÁ, I.; MAHARAJ, A.; VALLEJO, G.
Lugar:
Buenos Aires
Reunión:
Congreso; XXVI Reunion Anual de la Sociedad Latinoamericana de Endocrinología Pediatrica; 2016
Resumen:
Background: Primary adrenal insufficiency (PAI) is most commonly congenital in children and genetically heterogeneous. A third of patients have no genetic diagnosis, meaning their prog-nosis is uncertain. The association of PAI and nephrotic syndrome (NS) was observed in four families.Aim: To discover the genetic defect underlying this syndrome.Methods: Whole exome sequencing was performed in two families and Sanger sequencing to confirm segregation and screen further families.Case Reports: Argentinean siblings with PAI and NS born to consanguineous asymptomatic parents. The boy was admitted at 0.9 yrs with seizures and myocardial dilatation due to hypocalce-mia. Weight and height in 25th centile. He had skin hyperpigmen-tation, generalized ichthyosis and café au lait spot, micropenis, unilateral cryptorchidism and neurosensorial deafness. NS rapidly turned into chronic renal failure (CRF) stage V (biopsy: NS from first year). Lab: Cortisol 11.4 μg/dL, ACTH >1250 pg/mL, Aldoste-rone 182 pg/ml, LH 36 IU/L, FSH 58 IU/L, testosterone 1250 pg/mL). She developed CRF awaiting for kidney transplant. Presently (2 yrs) she has mild neu-rodevelopmental delay. Ultrasound showed bilateral enlarged ad-renal glands with unilateral hyperecogenic image inside in both patients. Sanger sequenciation revealed an homozygous canonical splice site change [c.261+1G>A; p.?] in SGPL1 (gene encoding sphingosine-1-phosphate lyase) in both patients and the same SGPL1 heterozygous mutation in their parents.