Alström syndrome is a rare genetic disorder caused by mutations in the gene ALMS1. It is among the rarest genetic disorders in the world, as currently it has only 266 reported cases in medical literature and over 501 known cases in 47 countries. It was first described by Carl-Henry Alström in Sweden in 1959. Alstrom syndrome is sometimes confused with Bardet-Biedl syndrome, which has similar symptoms. Bardet-Biedl syndrome tends to have later onset in its symptoms. The risk where two carrier parents can both pass the gene and therefore have a child affected by the syndrome is 25% with each pregnancy. The risk to have a child who is the carrier of the gene like the parents is 50% with each pregnancy. A chance for a child to receive normal genes from both parents and be considered to be "genetically" normal is 25%. The risk for carrying the gene is equivalent for both male and female.
Symptoms for Alström syndrome generally appear during infancy with great great variability in age. Some of the symptoms include:
- Heart failure (Dilated cardiomyopathy) in over 60% of cases, usually within the first few weeks after birth, but sometimes the onset is in adolescence or adulthood.
- Light sensitivity and vision problems (Cone-rod dystrophy) in all cases, usually within 15 months of birth and progressively worsening until about 20 years of age.
- Delays in early, developmental milestones in 50% of cases, learning disabilities in about 30% of cases.
- Obesity in 100% of cases, apparent by 5 years of age, but often apparent in infancy (Alström infants usually have normal birth weights, and by adolescence, weights tend to be in the high-normal to normal range).
- Nystagmus (usually affects the children) one of the first symptoms to occur which causes involuntary rapid eye movement.
- Heart failure (Dilated cardiomyopathy) in over 60% of cases, usually within the first few weeks after birth, but sometimes the onset is in adolescence or adulthood. (chronic)
- Mild to moderate bilateral sensorineural hearing loss.
- Type 2 diabetes usually occurs in early childhood.
- Hyperinsulinemia/ insulin resistance - development of high level of insulin in blood.
- Steatosis (fatty liver) and elevated transaminases (liver enzymes) often develop in childhood and can progress in some patients to cirrhosis and liver failure.
- Endocrine dysfunctions may occur where the patient may experience an under or over active thyroid gland, weak growth hormone, increased androgen in females, and low testosterone in males.
- Slowly progressive kidney failure can occur in the second to fourth decade of life.
Alström Syndrome is a rare genetic disorder that affects multiple organ systems of the body. This genetic disorder is caused by a mutation of the ALMS1 gene. The gene mutation is inherited as an autosomal recessive trait. This means both parents have to pass a copy of the ALMS1 gene in order for their child to have the syndrome even though the parents may not show signs or symptoms of the condition. It is still considered to be unknown on how the defective gene causes the disorder.
Prevention for Alström Syndrome is considered to be harder compared to other diseases/syndromes because it is an inherited condition. However, there are other options that are available for parents with a family history of Alström Syndrome. Genetic testing and counseling are available where individuals are able to meet with a genetic counselor to discuss risks of having the children with the disease. The genetic counselor may also help determine whether individuals carry the defective ALSM1 gene before the individuals conceive a child. Some of the tests the genetic counselors perform include chorionic villus sampling (CVS), Preimplantation genetic diagnosis (PGD), and amniocentesis. With PGD, the embryos are tested for the ALSM1 gene and only the embryos that are not affected may be chosen for implantation via in vitro fertilization.
The Jackson Laboratory in Bar Harbor, Maine, USA with the University of Southampton, UK isolated the single gene (ALMS1) responsible for Alström Syndrome. The gene is recessive; it must be passed from both parents for the syndrome to manifest.
It is possible to clinically detect Alström syndrome in infancy, but more frequently, it is detected much later, as doctors tend to detect symptoms as separate problems. Currently, Alström syndrome is often diagnosed clinically, since genetic testing is costly and only available on a limited basis.
A physical examination would be needed to properly diagnose the patient. Certain physical characteristics can determine if the patient has some type of genetic disorder. Usually, a geneticist would perform the physical examination by measuring the distance around the head, distance between the eyes, and the length of arms and legs. In addition, examinations for the nervous system or the eyes may be performed. Various imaging studies like computerized tomography scans (CT), Magnetic Resonance Imaging (MRI), or X-rays are used to see the structures within the body.
Family and personal medical history are required. Information about the health of an individual is crucial because it provides traces to a genetic diagnosis. Personal medical history may include past health issues, surgeries, hospitalizations, medications, allergies, and results of genetic or medical testing. Family medical history includes knowing the health of family members important for diagnosing the disorder. A physician may ask about a patient's parents, siblings, children, and other relatives. The Jackson Laboratory in Bar Harbor, Maine, USA with the University of Southampton, UK isolated the single gene (ALMS1) responsible for Alström Syndrome. The gene is recessive; it must be passed from both parents for the syndrome to manifest.
Laboratory tests, particularly genetic testing, are performed to diagnose genetic disorders. Some of the types of genetic testing are molecular, biochemical, and chromosomal. Other laboratory tests performed may measure levels of certain substances in urine and blood that can also help suggest a diagnosis. It is possible to clinically detect Alström syndrome in infancy, but more frequently, it is detected much later, as doctors tend to detect symptoms as separate problems. Currently, Alström syndrome is often diagnosed clinically, since genetic testing is costly and only available on a limited basis.
A prognosis for Alström syndrome is complicated because it widely varies. Any person that has the syndrome have different set of disorders. Permanent blindness, deafnesss, and Type 2 diabetes may occur. Liver and kidney failure can progressively get worse. The life expectancy is usually reduced and the patients barely live past 50 years old.
There is no cure for Alström syndrome; however, there are treatment aims to reduce the symptoms and prevent further complications. Some of these treatment aims include:
- Corrective lenses: tinted lenses that help with the sensitivity from bright lights. The patients may have to adapt to reading in Braille, use adaptive equipment, mobility aids, and adaptive computing skills.
- Education: patients with Alström syndrome suffering from intellectual disabilities must have access to education. They must be able to receive free and appropriate education. Some Alström syndrome patients are educated in normal classrooms. Other patients have to take special education classes or attend to specialized schools that are prepared to teach children with disabilities. Staff members from schools have to consult with patient's parents or caregivers in order to design an education plan based on the child's needs. In addition, the school may document the progress of the child in order to confirm that the child's needs are being met.
- Hearing aids: the battery-operated devices are available in three styles: behind the ear, in the ear, and inside the ear canal. Behind the ear aims for mild-to-profound hearing loss. In the ear aims for mild to severe hearing loss. Lastly, the canal device is aimed for mild to moderately severe hearing loss. Patients that have severe hearing loss may benefit from a cochlear implant.
- Diet: an appropriate and healthy diet is necessary for individuals with Alström syndrome because it could potentially decreases chances of obesity or diabetes.
- Occupational therapy: the therapist helps the child learn skills to help him or her perform basic daily tasks like eating, getting dressed, and communicating with others.
- Physical Activity: exercising reduces chances of being obese and helping control blood sugar levels.
- Dialysis: helps restore filtering function. With hemodialysis, a patient's blood circulates into an external filter and clean. The filtered blood is then returned into the body. With peritoneal dialysis, fluid containing dextrose is introduced into the abdomen by a tube. The solution then absorbs the wastes into the body and is then removed.
- Transplantation: patients that endure a kidney failure may undergo a kidney transplantation.
- Surgery: if the patient endures severe scoliosis or kyphosis, surgery may be require.
- Antibiotics: patients with lung problems will be prescribed antibiotics because they are more prone to infections like bronchitis.
- Oral diabetes medications: are taken by mouth to treat diabetes. Can be taken combined into a single pill, which may be more effective and convenient for people with diabetes. It is usually taken once or twice daily before meals. Some of these medications includes:
- Meglitinides (repaglinide and nateglinide): taken to stimulate the cells found in the pancreas to release insulin. These drugs are taken by mouth daily before each meal and could cause a drop in blood sugar. * Metformin (biguanide): decreases the amount blood sugar being released by the liver and by stimulating the cells within muscles to take up blood sugar. Taken twice daily. * Thiazolidinediones(rosiglitazone and pioglitazone): taken to help insulin work more efficiently in muscle and fat cells causing the liver to release less glucose. Is associated with heart failure. * Dipeptidyl peptidase IV (DPP-4) inhibitors (sitagliptin): helps with improving blood sugar levels by decreasing the action of an enzyme breaking down GLP-1 (lowers the blood sugar level).
- Injected diabetes medicine: taken by an injection into the fat below the skin. Sometimes referred as subcutaneous injections. Some of these medications include the following:
- Pramlintide (Symlin): is used as a synthetic form of insulin. Used to take up the extra blood glucose.
- Exenatide (Byetta): synthetic form of exendin-4 ( a substance that increases secretion of insulin in the pancreas). * Cholesterol-lowering medications: is necessary when cholesterol levels are high. HMG-CoA reductase inhibitors, also called "statins," effectively lower levels of low-density lipoprotein, cholesterol, and triglycerides. High-dose nicotinic acid (niacin) may also reduce cholesterol levels.
- Heart medications: Angiotensin-converting enzyme (ACE) inhibitors, diuretics, digoxin, and beta-blockers may help with the management of cardiomyopathy and heart failure