Alstrom syndrome is a rare, inherited genetic disorder affecting multiple organ systems throughout the body. Its effects are wide-ranging and progressive, with symptoms developing and changing from infancy through adulthood. The condition is caused by mutations in a single gene and impacts males and females equally across all populations.
Core Symptoms and Progression
One of the earliest features of Alstrom syndrome is vision loss that begins in infancy, caused by a cone-rod dystrophy where the retina’s light-sensing cells deteriorate. Infants often show a strong sensitivity to light (photophobia) and experience involuntary, rapid eye movements (nystagmus). This vision loss worsens over time, typically leading to severe visual impairment or legal blindness by adolescence.
Sensorineural hearing loss is another defining characteristic that often develops during childhood. Originating from issues within the inner ear or its nerve pathways to the brain, the impairment worsens with age, progressing from mild to profound.
Obesity often begins within the first few years of life, accompanied by an extreme, insatiable hunger known as hyperphagia. This early weight gain is closely linked to insulin resistance, where the body’s cells do not respond effectively to insulin. As a result, there is a high likelihood of developing type 2 diabetes, often during childhood or adolescence.
Systemic Health Complications
Alstrom syndrome also leads to health complications in major organs that can emerge at any stage of life. Individuals are at risk for cardiomyopathy, which affects the heart muscle. This can present as dilated cardiomyopathy, where the heart’s main pumping chamber is enlarged and weakened, or restrictive cardiomyopathy, where the chambers become stiff. These conditions can appear at any age, including in infancy, and are a factor in long-term health.
The kidneys are frequently affected by a slow but progressive decline in function, a condition known as nephropathy. This deterioration can eventually advance to the point of kidney failure, which requires intensive medical support.
Liver function can also be compromised by an accumulation of fat in the liver, a condition called hepatic steatosis. This is often more severe than expected based on body weight alone. Over time, this can lead to inflammation, fibrosis, and eventually cirrhosis, where scar tissue replaces healthy liver tissue and can lead to liver failure.
Genetic Cause and Diagnosis
Alstrom syndrome is caused by mutations in the ALMS1 gene. This gene provides instructions for making a protein involved in the function of cilia, which are microscopic, hair-like structures on cell surfaces. Cilia act as cellular antennas for communication and signaling pathways, and mutations in the ALMS1 gene disrupt this process, leading to the syndrome’s multi-system problems.
The condition is inherited in an autosomal recessive pattern. This means an individual must inherit two mutated copies of the ALMS1 gene—one from each parent—to be affected. The parents, who each carry one mutated copy, are considered carriers and do not show symptoms of the disorder.
Diagnosis begins with a clinical evaluation of characteristic symptoms like early vision loss, obesity, and hearing impairment. Because symptoms can overlap with other rare genetic disorders, a definitive diagnosis requires molecular genetic testing. This testing confirms the condition by identifying disease-causing mutations in both copies of the ALMS1 gene.
Management and Monitoring
There is no cure for Alstrom syndrome, but proactive management can address symptoms and improve an individual’s quality of life. The disorder’s complexity requires a multidisciplinary team of specialists to treat health issues as they arise. This team often includes:
- Cardiologists
- Endocrinologists
- Nephrologists
- Audiologists
- Ophthalmologists
Management is tailored to each person’s specific symptoms. For metabolic issues, this includes diet and exercise programs and medication to manage obesity and type 2 diabetes. For hearing loss, hearing aids or cochlear implants may be recommended to improve auditory function. While vision loss cannot be reversed, support services like orientation and mobility training help with navigating daily life.
Consistent monitoring is a part of the management plan. Regular evaluations of heart, kidney, and liver function are performed to detect any changes early. These check-ups can include echocardiograms to assess heart health, blood and urine tests to monitor kidney function, and imaging to check for liver disease. This ongoing surveillance allows the medical team to intervene and adjust treatment strategies as the condition evolves.