Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Alström Syndrome

Also known as Alström-Hallgren syndrome.

What is Alström Syndrome?

• Alström (pronounced Al-strom) syndrome is part of larger group of disorders known as rare genetic disorders of obesity.​​
• Alström syndrome is characterized by a progressive loss of vision and hearing, a form of heart disease that enlarges and weakens the heart muscle (dilated cardiomyopathy), obesity, type 2 diabetes (the most common form of diabetes), and short stature. ​
• Alström syndrome affects males and females in equal numbers. The exact incidence is unknown. 
• Because some cases of Alström syndrome may go unrecognized or misdiagnosed, the disorder may be under-diagnosed, making it difficult to determine its true frequency in the general population.

How Do You Get It?

• Alström syndrome is caused by genetic variants, or changes, in the ALMS1 gene.
• Estimates have ranged from 1 in 10,000 to less than 1 in 1,000,000 individuals in the general population.​
• Approximately 1200 affected individuals have been identified worldwide.
• Alström syndrome occurs with greater frequency in ethnically isolated communities.​

What Are The Symptoms?

• The signs and symptoms of Alström syndrome vary among affected individuals. The age that symptoms begin also varies. Symptoms may first appear anywhere from infancy to early adulthood.
• The absence of certain findings (e.g., polydactyly, intellectual disability) distinguishes Alström syndrome from similar syndromes such as Bardet-Biedl syndrome or Laurence-Moon syndrome.​​
• Signs and symptoms can include:
  • Vision abnormalities, specifically cone-rod dystrophy and cataracts; progresses to blindness​
  • Progressive sensorineural hearing loss in both ears and chronic infection or inflammation of the middle ear​
  • Heart disease that enlarges and weakens the heart muscle (dilated cardiomyopathy)​
  • Excessive eating (hyperphagia) and rapid weight gain leading to obesity
  • Insulin resistance leading to high levels of insulin in the blood (hyperinsulinemia) and type 2 diabetes mellitus
  • Elevated levels of fats (lipids) in the blood (hyperlipidemia)
  • Fatty liver that may progress to significant liver disease​
  • Short stature
  • Skin findings including abnormally increased coloration and “velvety” thickening of the skin in certain areas of the body (acanthosis nigricans)
  • ​Lower hormone levels produced by the male testes or the female ovaries (hypogonadism)
  • Alström syndrome can also cause serious or life-threatening medical problems involving the liver, kidneys, bladder, and lungs.​

How Is It Treated?

• There is no cure for Alström syndrome, but careful monitoring of vision, hearing, liver, heart, thyroid, and kidney function is important for detecting and treating symptoms early. There is no specific treatment for Alström syndrome.
• Treatment is focused on managing the symptoms present in each individual. This may involve a team of specialists including but not limited to: pediatricians, cardiologists, audiologists (hearing specialists), ophthalmologists, endocrinologists, and orthopedists.
• No disease-modifying therapies have been approved for this disease.
• Patients and their families benefit greatly from seeking social and emotional support to cope with the isolation that may come with living with a rare and complicated disorder.
• Management should include vigilant monitoring and treatment of the emerging clinical manifestations.​
  • ​Red-orange tinted prescription lenses can reduce photophobia.
  • As blindness occurs in all cases, early educational planning to teach patients Braille, computing skills and adaptive living skills is essential. ​
  • Bilateral digital hearing aids can increase hearing capabilities. Heart failure is mainly treated with angiotensinogen-converting enzyme (ACE) inhibitors, diuretics, and digoxin.
  • Diabetes can be managed with a low-fat, low sugar diet, exercise, metformin, glitazones and incretin analogues (beneficial in 2/3 of cases). ​
  • Beta-blockers, sclerotherapy of the esophageal veins, and banding usually treat portal hypertension. ​
    • In unsuccessful cases a transjugular intrahepatic portosystemic shunt may be needed. In those with renal disease, ACE inhibitors can be considered. ​
    • In several cases, renal transplantation has been successful.​
• The prognosis for Alström syndrome varies depending on the progression of symptoms, specifically heart and kidney disease.
• The lifespan and overall quality of life for individuals with Alström syndrome can be improved by early diagnosis, treatment, surveillance, and proper management of symptoms.​
• Prognosis is highly variable due to the range of disease presentations.
• Alström syndrome is associated with a number of chronic life-threatening issues, such as congestive heart failure and end-stage renal disease, the two major causes of death.
• Death typically occurs before age 40.

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this disease from Alström Angels.