Alström Syndrome · What It Is, Causes, Signs and Symptoms, and More

Signs and symptoms of Alström syndrome depend on the severity of the condition and the body systems affected. In general, symptoms usually develop during infancy or childhood, and progressively worsen throughout one’s life. Sensory deficits are a common finding in children with Algröm syndrome and can include vision changes, like cone-rod dystrophy, which is when the cones and rods in the retina start to deteriorate causing vision loss; photophobia, or light sensitivity; and nystagmus, or abnormal rapid eye movements. Usually, vision changes will present soon after birth with complete blindness usually occurring by the second decade of life. Hearing changes can also occur with Alström syndrome, specifically, sensorineural hearing loss, which can be progressive and can affect both ears.  

Patients with Alström syndrome may also have issues with chronic inflammation and infections of the middle ear, also known as otitis media. Individuals may experience conductive hearing loss related to the build-up of sticky ear fluid behind the eardrum, also known as adhesive otitis media or more colloquially, glue ear. Other chronic infections may involve both the respiratory and the urinary tracts. 

Patients with Alström syndrome often present with clinical manifestations that are caused by endocrine abnormalities, like hypertriglyceridemia, abnormal bone growth, obesity, insulin resistance, and type 2 diabetes mellitus. Before puberty, children are noted to have rapid growth and typically present at heights above the 50th percentile for the age; however, early growth velocity tends to decline with age, resulting in short stature in adulthood. Obesity, or more specifically, truncal obesity, is a fat buildup in the abdomen and is a common characteristic of Alström syndrome that is seen during childhood. Insulin resistance and diabetes can occur with Alström syndrome related to the body's inability to use insulin and glucose correctly. Additionally, patients with Alström syndrome can also develop acanthosis nigricans, which is a skin condition related to insulin resistance, resulting in hyperpigmentation and a thickened appearance. Another endocrine abnormality is hypogonadism, which may be seen in both males and females, though is more common in males.  

Individuals may also experience organ system dysfunction involving the heart, liver, and kidneys. Dilated cardiomyopathy, which is an enlarged heart muscle that has difficulty pumping, can occur with Alström syndrome. This can eventually lead to congestive heart failure, where the heart is unable to pump blood to meet the demands of the body’s tissues. Hepatic disease may present initially with clinically silent elevations in transaminases (i.e., AST, ALT) and steatosis, proceeding to significant fibrosis, cirrhosis, portal hypertension, esophageal varices, hepatic encephalopathy, and end-stage liver disease. Finally, renal failure and liver failure can occur later in life as a result of glomerulosclerosis.  

Alstrom syndrome is usually suspected based on clinical manifestations, however, molecular genetic testing is required for confirmation. The presence of two mutated alleles, which are mutated versions of genes, or one mutated ALMS1 allele along with four clinical manifestations is usually considered a positive indication for Alström syndrome. Diagnosing Alstöm syndrome may be difficult due to the delayed onset of some clinical manifestations.  

Usually, a variety of other tests will be performed to rule out other possible conditions, like various mitochondrial disorders and early-onset severe retinal dystrophy. These can include eye tests, like an electroretinogram (ERG), which can visualize any changes to the retina, and an electrooculogram (EOG), which can assess retinal function. Other exams like an electrocardiogram (ECG), as well as blood tests, can be completed to help differentiate other heart and endocrine disorders from Alström syndrome. Hearing tests will also usually be performed and usually include audiometry.