Alström syndrome is a serious multisystem inherited disease that can be diagnosed early in life. Birth weight is usually normal, but truncal obesity develops in the first year of life. Insulin-resistant type 2 diabetes with hyperinsulinemia is often accompanied by hypothyroidism and hypogonadotropic hypogonadism (especially evident in males). The majority of patients are short in stature (25th percentile), perhaps as the result of growth hormone deficiency, but kyphoscoliosis, which occurs in 30%-70% of patients, also likely contributes. Acanthosis nigricans can be a feature in patients with type 2 diabetes. Dilated or restrictive cardiomyopathy occurs among 70% of children in the first months of life, but some infants recover. Others may develop cardiac failure later in life. Pulmonary disease such as chronic bronchitis and asthma can lead to respiratory symptoms. Dyslipidemia (usually hypertriglyceridemia) is commonly present. Hepatomegaly with elevated liver enzymes may be detectable in the first decade, followed by cirrhosis. Urinary tract infections are common, while progressive interstitial disease frequently results in kidney failure later in life.

Severe sensorineural hearing loss is evident in 70% of individuals within the first decade of life. Retinal rods and cones undergo progressive deterioration in the first year, resulting in poor vision, photophobia, and nystagmus. The electroretinogram shows receptor damage in the first year of life, and responses are completely extinguished by the second and third decades of life. Most patients are legally blind by the end of the first decade, and even light perception is lost by the second decade for those that live that long. Intelligence is usually normal, but more than 50% of patients have some delay in achievement of developmental milestones. There is considerable variability in clinical manifestations, but lifespan is generally shortened and many patients die in childhood. Few patients live beyond age 40.