P-339: Alström syndrome unmasked by poor glycemic control in an 8-year-old child initially diagnosed with leber congenital amaurosis and type 1 diabetes
M Lenza Resende, A Z Schroeder, D S B Barreto, R M B Novaes, D R Bertolla, D A d M Athayde, B Sannicola, B S Kann, C G B PassoneAbstract
Introduction
Alström syndrome is a rare ciliopathy characterized by progressive multisystem involvement, including cone-rod dystrophy, obesity, insulin resistance, type 2 diabetes, dyslipidemia, and hepatic dysfunction. Because its clinical manifestations develop gradually and vary among patients, the diagnosis is frequently delayed.
Objectives
To report a child initially followed for Leber congenital amaurosis and T1D in whom severe insulin resistance, hypertryglyceridemia and difficult-to-control diabetes led to the diagnosis.
Methods
An 11-year-6-month-old female patient was referred to our clinic by the Ophthalmology Department, where she had been followed for Leber congenital amaurosis, due to poorly controlled diabetes mellitus (Hb1Ac=11.2%). At 8 years-old, she developed severe hyperglycemia requiring insulin therapy, along with hypertriglyceridemia (513 mg/dL) and moderate hepatic steatosis.
Results
At the initial evaluation, she was overweight, Tanner stage B3P4, without acanthosis nigricans, and presented with hand arthropathy and severe visual impairment.The patient received diabetes education, and her basal–bolus insulin regimen was optimized. Her family history was notable for a brother who died at 7 years of age from pulmonary disease and had congenital amaurosis and hypertriglyceridemia. Because of persistent hyperglycemia, she was admitted for intensive glycemic management. Her total daily insulin dose was progressively increased from 2.0 to 4.2 IU/kg/day. She achieved 50% time in range with no episodes of hypoglycemia.Whole-exome sequencing identified a pathogenic variant consistent with Alström syndrome. Metformin therapy was initiated, and further evaluation revealed bilateral sensorineural hearing loss.
Conclusions
Marked insulin resistance prompted further investigation of other forms of diabetes. The diagnosis of Alström syndrome, despite its atypical presentation, significantly changed the patient’s prognosis, multidisciplinary follow-up, and therapeutic approach.