Alström syndrome

Overview

Alström syndrome is a rare, progressive, multisystem genetic disorder that affects numerous organs and systems in the body. It is characterized by a combination of vision and hearing loss, obesity, type 2 diabetes mellitus, and cardiomyopathy. Other features may include liver, kidney, and lung dysfunction. The onset and severity of symptoms vary widely among individuals, even within the same family. Alström syndrome is often compared to Bardet–Biedl syndrome, though the two are genetically distinct.

Causes

Alström syndrome is caused by mutations in the ALMS1 gene, which is located on chromosome 2 (2p13). This gene plays a critical role in the function of cilia—microscopic structures involved in cellular signaling and organ development. Mutations in ALMS1 disrupt normal ciliary function, leading to widespread systemic effects.

The condition follows an autosomal recessive inheritance pattern, meaning a person must inherit two defective copies (one from each parent) to develop the syndrome. Carriers (with one mutated copy) typically show no symptoms.

Symptoms

Alström syndrome presents with a broad range of clinical features, often appearing in early childhood and worsening over time. Common signs and symptoms include:

Ophthalmologic:

• Photophobia (light sensitivity) in infancy

• Nystagmus (involuntary eye movement)

• Progressive vision loss due to cone-rod dystrophy

• Blindness, often by the second decade of life

Auditory:

• Sensorineural hearing loss, typically developing in childhood

• Progressive and bilateral

Metabolic and Endocrine:

• Childhood obesity

• Insulin resistance and early-onset type 2 diabetes mellitus

• Hypertriglyceridemia and other lipid abnormalities

• Hypothyroidism (in some cases)

Cardiac:

• Infantile dilated cardiomyopathy

• Congestive heart failure (can be recurrent or chronic)

Other Features:

• Kidney and liver dysfunction

• Pulmonary fibrosis or chronic lung disease

• Delayed motor and speech milestones

• Progressive renal failure

• Male hypogonadism or delayed puberty

Diagnosis

Diagnosing Alström syndrome can be challenging due to its overlap with other syndromes and the wide variability in presentation. Diagnostic steps include:

• Clinical evaluation: Based on multisystem involvement including vision, hearing, metabolic, and cardiac findings

• Electroretinography (ERG): To detect cone-rod dystrophy

• Audiologic testing: To assess hearing loss

• Echocardiogram: For cardiomyopathy assessment

• Blood tests: To check glucose, insulin levels, liver and kidney function, and lipid profile

• Genetic testing: Definitive diagnosis through identification of biallelic mutations in the ALMS1 gene

Treatment

There is no cure for Alström syndrome. Treatment is supportive and focuses on managing complications and slowing disease progression through a multidisciplinary approach:

Vision and Hearing:

• Low vision aids, braille instruction, and orientation training

• Hearing aids or cochlear implants

Metabolic and Cardiac Care:

• Diet and exercise programs for obesity and diabetes management

• Oral hypoglycemics or insulin therapy

• Cardiac medications and monitoring for heart failure

Organ-Specific Management:

• Renal and liver function monitoring

• Dialysis or transplantation in end-stage renal disease

• Respiratory therapy for lung involvement

Developmental and Educational Support:

• Early intervention services

• Special education and speech therapy

Prognosis

The prognosis for individuals with Alström syndrome depends on the severity and progression of organ involvement. While cognitive function is usually preserved, most individuals face progressive vision and hearing loss, as well as life-threatening complications such as heart or kidney failure. Many individuals survive into adulthood, but life expectancy may be reduced, particularly if cardiomyopathy or renal failure occurs early or is severe.

Ongoing monitoring and multidisciplinary care can help improve quality of life and delay the progression of complications.