In 1959, the Swedish physicist Carl Henry Alström first described Alström’s syndrome. This is an extremely rare, hereditary genetic disease that affects approximately nine hundred patients worldwide. The cause is a mutation (change) in the hereditary material. The condition has a range of possible symptoms, but the main features are obesity throughout life, insulin resistance resulting in later diabetes mellitus 2, blindness due to congenital retinal dystrophy and hearing loss. Scientists are still working on the exact cause and treatment for this syndrome.
- Epidemiology Alström syndrome
- Symptoms include eyes, ears, liver, lungs and heart
- Diagnosis and examinations
- Therapy
- Heredity
- Life expectancy
- Contact groups for patients
- Centers of expertise
Epidemiology Alström syndrome
An estimated nine hundred patients worldwide suffer from Alström syndrome. The condition occurs in all nationalities, ethnic groups and races. In the Netherlands there are only around ten known patients. Very few research reports are known in the literature; this reflects how extremely rare this condition is.
Symptoms include eyes, ears, liver, lungs and heart
Several symptoms occur in Alström syndrome. The syndrome is progressive, meaning it worsens and more symptoms appear over time. The organs eventually fail. It depends on the individual whether and, if so, to what extent the following symptoms present themselves.
Obese
Most often, patients suffering from Alström syndrome are obese.
Eyes
Visual impairment or blindness: The first symptoms are already visible in the first year of life. For example, nystagmus (medical term: involuntary rapid eye movements) and photophobia (hypersensitive to light) occur. This leads to retinal degeneration, making blindness possible at any age.
Ears
Hearing develops between the ages of 1 and 10. Children usually become hearing impaired before they reach the age of 10. Initially, hearing loss concerns the high frequencies. The brain does not receive auditory information because the hearing loss is related to the loss of nerve function. The patient is advised to have a regular hearing examination so that the ear specialist is able to monitor the hearing loss.
Liver
Furthermore, various liver function disorders are possible, such as: Portal hypertension (high blood pressure in the hepatic portal vein (> 12 mm/Hg)), steatosis (fatty liver) and elevation of liver enzymes.
Lungs
Patients suffering from Alström’s syndrome regularly have lung problems such as bronchitis (inflammation of the tracheal branches) and COPD. COPD is the abbreviation of Chronic Obstructive Pulmonary Diseases. This is a collective name for chronic, irreversible and diffuse narrowing of the airways (chronic obstructive pulmonary disease). The lungs are always full of small inflammations that cause permanent damage. There is no treatment for COPD. Symptoms include shortness of breath when climbing stairs, working or dressing. In addition, there is increased mucosal secretion (hypersecretion of the lungs), lung infections (pneumonia: inflammation of the lower respiratory tract) sometimes occur, a patient suffers from respiratory infections and/or pulmonary hypertension. The latter is a chronic and rare lung disease because the pressure in the blood vessels of the lungs is too high
Heart
Dilated cardiomyopathy)
This causes the heart muscle to relax, causing one or more heart cavities to dilate. The opening and closing of the heart valves is therefore less efficient, which increases the risk of a heart valve leaking. The pumping force also decreases in a dilated heart. Especially during exercise, less blood than normal passes through the body.
Congestive cardiomyopathy
The heart has difficulty pumping blood to all parts of the body. This results in fluid and blood accumulation in the lungs, causing shortness of breath. Swelling of the feet, ankles and legs is also possible.
Restrictive cardiomyopathy
Restrictive cardiomyopathy means that the muscle tissue of the heart changes into stiff connective tissue, causing the heart muscle to no longer relax properly. As a result, the heart chamber does not fill sufficiently with blood. An increase in blood pressure in the atria occurs and the wall of the atria thickens. In a later stage, the atria dilate (widen), making heart rhythm disturbances (atrial fibrillation) or heart failure (poor pumping of blood through the heart) possible.
During puberty or later, three different cardiomyopathies (inflammation of the heart muscle) may occur: dilated cardiomyopathy , congestive cardiomyopathy and restrictive myopathy.
Other symptoms
Other symptoms of patients suffering from Alström syndrome occur with aging. These include:
- Alopecia: Bald spots on the head (hair loss)
- Asthma or breathing problems
- Diabetes insipidus: This has nothing to do with the well-known diabetes mellitus. In diabetes insipidus, the body’s control mechanism for fluid absorption and fluid excretion no longer works properly. Patients with diabetes insipidus feel very thirsty, urinate very large amounts (polyuria), and urinate frequently (pollakisuria) because the kidneys are constantly excreting water. This increases the risk of dehydration, which may lead to low blood pressure, high heart rate (tachycardia) and constipation.
- Diabetes mellitus: diabetes mellitus
- Perpetual hunger: Patients with Alström have no feeling of satiety. This is a major problem, especially for babies and young children (but also for many young adults and adults). They always live with the feeling of being hungry, which is frustrating because they have to limit themselves to what is averagely healthy to eat, while they still receive signals of hunger.
- Frequent urinary tract infections
- Gastroesophageal reflux: Backflow of stomach contents into the esophagus and then to the mouth
- Advanced bone age: Higher age bone growth than actual age person
- Hirsutism, hyperandrogenism: Excessive hairiness
- Hyperlipidemia: Various disorders in lipid metabolism
- Hyperostosis frontalis interna: Frequently occurring benign thickening of the inside of the frontal bone of the skull. The doctor often sees this in women after menopause. However, this happens at a much younger age in patients with Alström and is not tied to gender, as virtually no one with Alström syndrome ever reaches menopause)
- Hypertension: High blood pressure increases the risk of disease
- Hyperuricemia (increased uric acid levels in the blood)
- Hypothyroidism: Underactive thyroid gland
- Low level of growth hormone: Not fully growing (growth hormone deficiency: condition involving a lack of growth hormones)
- Low level of testosterone: This causes testicles and sexual organs to develop incompletely. In addition, men’s beards do not reach their throat as much, which means they have a high-pitched voice.
- Kidney failure (reduced or absent kidney function): Due to all kinds of problems with the kidneys in combination with diabetes, the kidneys often deteriorate rapidly and dialysis is a possibility.
- Kidney poisoning: This occurs around the age of 20 to 40.
- Irregular menstruation with the risk of infertility (female infertility)
- Scoliosis: Lateral curvature of the spine
- Splenomegaly: Enlarged spleen
- Darkening of areas of the skin
- Prematurely worn joints
Diagnosis and examinations
Diagnosis of the disease
The diagnosis is made on the basis of the above characteristics, but sometimes the diagnosis can be confirmed with genetic testing. Nevertheless, the diagnosis is sometimes difficult because some symptoms are congenital (innate), while others only arise during the child’s development.
Differential diagnosis
Furthermore, this syndrome can sometimes be confused with Bardet-Biedl syndrome. However, this usually involves an intellectual disability as well as abnormalities of the hands and feet, while this is not the case with Alström syndrome.
Therapy
There is no treatment available for this disease, but it is possible to use supportive treatment to relieve the symptoms. Because there is a whole list of symptoms, regular and intensive follow-up by various medical disciplines is necessary.
- Diabetes: diet, medication and/or insulin, pancreas transplant
- Heart problems: medication, sometimes surgery or a transplant
- Kidney disorders: kidney transplants, often in combination with the pancreas
- Hearing impairment: hearing aid or a cochlear implant (CI)
- Visual impairment: special glasses, reading aids, mobility training, braille, etc.
Heredity
The inheritance of Alström syndrome is autosomal recessive. The disease can only be passed on to the child if both parents are carriers of a mutated gene (ALMS1 mutation). The parents themselves are not ill, they are just carriers of a mutated gene and therefore pass it on to the child without even knowing it. In most cases, there is no previous family history of the condition.
Life expectancy
According to the literature, the life expectancy of patients suffering from Alström’s syndrome rarely exceeds 40 years, but there are many known cases of patients living longer. Many patients die before the age of thirty.
Contact groups for patients
The Alström Syndrome Foundation The Netherlands supports patients and their family members and brings them into contact with each other. This foundation also has a YouTube channel with videos of activities for the benefit of the foundation. There is also a page of Denan and Milan on Facebook, related to the Alström The Netherlands Foundation. There is no contact group or patient association in Belgium. There are also groups on Facebook such as Alström UK. Alström in America is very active in the field of research and development. There is also a German-speaking peer group.
Centers of expertise
There is (yet) no expertise center for this disease in Belgium and the Netherlands. They are working on it in England and in America there is a large center that is very accessible to patients from abroad: http://www.alstrom.org.uk.
read more
- Boucher-Neuhäuser Syndrome: Eye abnormalities and ataxia
- Dekaban-Arima syndrome: Absent cerebellum
- Bálint’s syndrome: Being “seeing blind”.
- Bonnet’s syndrome (visual hallucinations)
- Wolfram syndrome: Neurodegenerative disorder
