The role of an ophthalmologist in the Alström syndrome diagnosis

The Alström syndrome (AS) is an extremely rare autosomal recessive genetic disorder, affecting less than 1: 1,000,000 people globally. It is a single gene disorder, due to the mutation of ALMS1 on chromosome 2 (2p13). The AS affects multiple organs and systems. Approximately 800 affected individuals have been identified worldwide so far. Some cases of the AS may go unrecognized for years as many of the clinical features develop over a longer period of time. As the nystagmus and retinitis pigmentosa are the most consistent findings, usually the first visible sign and that at the early infant period, the main aim of this article is to emphasize the importance of the ophthalmologist in establishing an adequate diagnosis of this rare syndrome. Case Report: This article describes a Serbian patient with Alström syndrome, whose diagnosis was genetically confirmed using the whole exome sequencing. Our case was a 7year-old male with symptoms of progressive visual impairment, photophobia and nystagmus diagnosed in early childhood. On admission, the bilateral visual acuity was poor, RE 0,06, LE 0,01, the intraocular pressure within range. The funduscopy showed central retinal pigmentation, thus suggesting cone-rod retinal dystrophy with “bull’s eye maculopathy”. The initial laboratory work at the time of the consultation revealed elevated triglycerides levels and hyperinsulinemia, increased transaminases and gamma-glutamyl transpeptidase serum activity, whereas the glucose and HbA1C levels were normal. The bilirubin test results were normal. Overall, the clinical manifestations were absent. The patient’s cardiac function was normal and the echocardiography did not indicate any abnormalities at the time. His sensorineural hearing was normal as well. A molecular genetic analysis was performed. Two composite heterozygous mutations were discovered within the ALMS1 gene sequence. In addition to the clinical presentation, the mutation detection confirmed the initial diagnosis of the AS. Conclusion: The Alström syndrome should be kept in mind in the case of an obese child with photophobia, nystagmus and visual impairment present from early childhood. Fundus examination by an ophthalmologist may significantly help establish the diagnosis of this rare genetic syndrome. Apstrakt Uvod Alstromov syndrome (AS) je veoma retko autosomno recesivno oboljenje koje se javlja sa prevalencijom manjom od 1:1 ljudi širom sveta. To je oboljenje gena ALMS1 na hromozomu 2 (2p13) koji utiče na više sistema organa. Do sada, oko 800 ljudi širom sveta ima dijagnostikovan AS. Neki slučajevi AS mogu da budu neprepoznati s obzirom na to da se mnoge kliničke karakteristike razvijaju tokom vremena. Kako su nistagmus i distrofija retine najdosledniji nalazi, koji se obično pojavljuju prvo, u ranom detinjstvu, želimo da ukažemo na značaj oftalmologa u postavljanju dijagnoze ovog retkog sindroma. Prikaz bolesnika U ovom radu, opisujemo pacijenta sa Alstromovim sindromom čija dijagnoza je potvrđena genetskom analizom sekvenciranja celog egzoma. U pitanju je 7-godišnji dečak sa simptomima progresivnog smanjenja vida, fotofobijom i nistagmusom koji su počeli u ranom detinjstvu. Početna oštrina vida je bila na oba oka skromna, desno oko 0,06, levo oko 0,01, intraokularni pritisak u normalnim granicama. Na fundusu se videla centralna retinalna pigmentacija koja je ukazivala na cone-rod retinalnu distrofiju sa “bull’s eye maculopathy”. Laboratorijski nalazi su ukazali da su trigliceridi blago povišeni. Glukoza i HbA1C su bili u normalnim granicama, ali je bila prisutna hiperinsulinemija. Takođe, enzimi transaminaze i gamaglutamil transpeptidaze su bili povišeni, Vrednosti bilirubina su bile u granicama referentnih vrednosti. Kardiološki i ehokardiografski nalaz su bili uredni. Ispitivanje sluha je bilo u granicama referentih vrednosti. Sprovedena je molekularna genetska analiza. Dve složene heterozigotne mutacije su nađene na ALMS1 genu koje su uz prisustvo kliničkih manifestacija potvrdile dijagnozu AS. Zaključak O Alstromovom sindromu treba razmišljati kada imamo gojazno dete sa fotofobijom, nistagmusom i smanjenjem vida koje datira od ranog detinjstva. Pregled fundusa od strane oftalmologa može da bude od velikog značaja, i da podstakne sumnju na ovaj redak genetski sindrom.