First Author: J.Karadzic SERBIA
Co Author(s): J. Pantelic D. Risimic J. Jaksic I. Kovacevic
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Alstrom's syndrome (AS) is a rare genetic disorder affecting less than 1: 1,000,000 people globally. It's a single gene disorder of ALMS1 on chromosome 2 that affects multiple systems. The characteristic features of this syndrome are cone-rod retinal dystrophy causing juvenile blindness, sensorineural hearing loss, childhood truncal obesity, hyperinsulinemia and insulin resistance, type 2 diabetes mellitus, hypertriglyceridemia, dilated cardiomyopathy, progressive pulmonary, hepatic, and renal dysfunction. Some cases may go unrecognized or misdiagnosed as many of the clinical features develop over time, as child grows. Diagnosis is usually set on the basis of established clinical criterion often without genetic confirmation.
We have an opportunity to present a patient with Alstrom's syndrome whose diagnosis was genetically confirmed. As the nystagmus and retinitis pigmentosa are the most consistant findings, presented usually first, at early childhood, we want to highlight the importance of the ophthalmologist in clinching the diagnosis of this rare syndrome.
Our case was a 7-year-old male who referred to our clinic due to progressive visual impairment, photophobia, and nystagmus started from early childhood. His preliminary diagnosis was cone-rod retinal dystrophy. Patient was born as a second child of a two children family, from a normal pregnancy and delivery. At 9 months old, a nystagmus was observed and retinal dystrophy was diagnosed. He experience difficulty with light but sees better in darkness. He was reported to have no mental retardation or any signs of motor delay. On both eyes, admission visual aquity was poor, RE 0,06, LE 0,01, intraocular preasure within range. In the neurological examination, both pupil was round in shape and midsize (3.5 mm), with normal response to light. No abnormalities in the eye movements were detected except the horizontal nystagmus. Fundoscopy showed central retinal pigmentation suggesting cone-rod retinal dystrophy with “bull’s eye maculopathy”. Perimetry showed bilateral constriction of visual field.
The initial labwork at the time of consultation revealed an elevated triglyceride with a high density lipoprotein cholesterol. His glucose and HbA1C levels were normal, while it was observed hyperinsulinemia. His transaminases and gamma-glutamyl transpeptidase were elevated but overt clinical manifestations were absent. The abdominal ultrasound showed evidence of steatosis, with normal liver and spleen measurements. On physical examination, there was evidence of central obesity with his body mass index (BMI) being 26,1 kg/m2. His cardiac function was normal as well as his sensorineural hearing. Echocardiography did not indicate any abnormalities at time. Blood urea nitrogen, creatinine and uric acid were normal. Renal and tubular echocardiography did not indicate any abnormalities. In our patient, molecular genetic analysis was performed. The coding sequences of exons 16 and 19 of ALMS1 were PCR-amplified, purified, and products were directly sequenced according to standard methods. As a result, two composite heterozygous mutation were discovered in the gene ALMS1: two nucleotide variations in exons 16 and 19 of the gene ALMS1. A heterozygous ALMS1 mutation detected in exon 16 and 19, along with the clinical present confirmed the diagnosis of AS.
In this study, we want to present a patient with Alstrӧm syndrome whose diagnosis was genetically confirmed using whole exome sequencing. Alstrom syndrome should be kept in mind while investigating an obese child with photophobia, nystagmus and visual impairement started from the early childhood, and fundus examination by an ophthalmologist can be of significant help in hinting the diagnosis of this rare genetic syndrome especially because there is no cure for this condision and detailed multidisciplinary approach is recommended in order to prevent further complications.