Alström syndrome is a genetic disease that manifests early during childhood. It affects the entire organ system and is associated with a short life expectancy.
What is Alström syndrome?
Alström syndrome is an extremely rare inherited disorder that affects only a few hundred children and adults worldwide. Alström syndrome is an extremely rare inherited disorder that affects only a few hundred children and adults worldwide. The syndrome is inherited in an autosomal recessive manner and belongs to the group of ciliopathies. It is characterized by a variety of symptoms affecting a wide range of organ systems that become more severe and complex with age. Classical is the early development of photophobia and nystagmus. Usually, as a result of progressive visual impairment, complete blindness occurs before the onset of puberty. In addition to disturbances of metabolism and hormonal system, kidneys, liver and heart are also affected by the disease. The cognitive abilities of the patients are not impaired. The syndrome was named after the Swedish physician Carl Henry Alström, who first described the clinical picture in 1959.
Causes
Alström syndrome is passed on to offspring via an autosomal recessive mode of inheritance. Both parents carry a mutation of the gene ALMS1 on chromosome 2p31, which does not become expressed in its heterozygous form. Only when the gene defect is present in homozygous form in the genome does the classic clinical picture develop. The gene ALMS1 codes for a large protein, which can be detected in the centrosome of almost all body cells and is related to the cilia function or the function of the cilia-bearing cells. Alström syndrome thus belongs to the group of ciliopathies. Due to the numerous and diverse function of the cilia, the exact disease etiology is not yet clear. This continues to be a central topic of many research groups.
Symptoms, complaints, and signs
Most symptoms of Alström syndrome appear during early childhood and worsen with age. For example, affected children usually develop photophobia and nystagmus shortly after birth. As childhood progresses, vision deteriorates until children usually become completely blind by the age of twelve. Vision damage is joined by hearing damage during childhood. Heart problems such as dilated cardiomyopathy (a disease of the heart muscle) or sudden heart failure also often occur during childhood, but may not manifest until adolescence or adulthood. Children are often overweight, suffer from insulin resistance or type 2 diabetes, and have elevated blood lipid levels. Other symptoms are varied, ranging from infertility and thyroid disorders to typical facial features, thin hair or darkening of the skin. It is not uncommon for children to exhibit short stature or curvature of the spine.
Diagnosis and course
Because of the variety of symptoms that manifest only as the disease progresses, diagnosis of the syndrome is rare. Often, it is not until adolescence or adulthood that the complex complaints can be interpreted as Alström syndrome based on their constellation. If the disease is suspected, the diagnosis can be confirmed by molecular genetics. However, genetic testing is often not performed due to its low sensitivity. The changes in the eye contribute significantly to the diagnosis. In the course of the disease, all patients develop nystagmus and photophobia very early, leading to non-inflammatory retinal disease and eventually to complete blindness before reaching adolescence. Even before ocular symptomatology, heart failure due to myocardial disease can often be diagnosed. The risk of heart failure thus already exists in early childhood and persists into adulthood. Early on, children become overweight, and after puberty they usually suffer from insulin resistance and even type 2 diabetes. Loss of hearing ability from the age of 10 is also classic. Progressive liver and kidney damage leads to kidney failure, especially in the second to fourth decade of life.
Complications
Alström syndrome is characterized by a variety of disorders and symptoms, the course of which becomes increasingly complex as patients age. A reliable prognosis on the course of the disease is further complicated by the fact that it is a very rare hereditary disorder affecting only a few hundred patients worldwide in childhood and adulthood. The symptoms and the associated health impairments already occur in early childhood and worsen in the following years of life. Light sensitivity and uncontrolled eye tremors are characteristic. Patients’ vision deteriorates to the point of blindness by age 12. Heart problems and heart failure usually occur in childhood, but may not become apparent until adolescence or adulthood. Children often suffer from obesity, insulin resistance, and type 2 diabetes. Other disorders are varied, ranging from thyroid disorders and infertility to thin hair, distinctive facial features, and darkly discolored skin. From the age of 10, children lose their hearing. Typical of Alström syndrome is a curved spine. Kidney failure often presents in the second to fourth decade of life. Diagnosis is delayed in many cases because the complex symptoms and disorders are often misdiagnosed due to low sensitivity to this rare ciliopathy. Because of the multiple organ disease, life expectancy is low even with appropriate treatment and individual therapies, as few patients reach the age of 40.
When should you see a doctor?
In general, Alström syndrome is associated with a severe reduction in the patient’s life expectancy. Therefore, treatment by a physician can only relieve the symptoms, but not completely cure them. A doctor should be consulted if the child develops significant visual disturbances at a young age, which continue to progress. It is not uncommon for this to lead to complete blindness. Likewise, any existing heart problems must be treated properly so that sudden cardiac death does not occur. A doctor can also be consulted if the patient’s resilience suddenly drops sharply for no particular reason. Furthermore, the syndrome not infrequently causes psychological discomfort, which can occur not only in the patients themselves, but also in their parents and relatives. Here, too, treatment by a psychologist is necessary to prevent depression and further upsets. In most cases, life expectancy is reduced by Alström syndrome to about 40 years.
Treatment and therapy
Because Alström syndrome is a genetic inherited disease whose pathogenesis is not clearly understood, treatment can only be symptomatic. Care of patients in a specialized center is essential, because many symptoms can be attenuated or even prevented by an appropriate therapeutic offer and a preventive lifestyle. The heart should be examined regularly by means of cardiac echocardiography to check the functionality of the heart muscle. Blood tests, blood pressure measurements and weight reduction can be used to counteract the development of insulin resistance or type 2 diabetes at an early stage or to intervene with medication in good time. Early blindness can be delayed by wearing special filtering glasses and mobility exercises. Early learning of Braille also improves patients’ quality of life. Medications to treat heart, thyroid, liver, and kidney disorders can be administered, provided close examinations are performed. Organ transplants can be performed if necessary, but are critical because of the multi-organ disease and the prognosis of the disease. Despite therapeutic measures that mitigate the course of the disease and improve the patient’s quality of life, few patients have a life expectancy of more than 40 years.
Outlook and prognosis
Alström syndrome significantly reduces the patient’s life expectancy in most cases. Because the syndrome occurs in childhood, it can also have a negative psychological impact on the patient’s parents and relatives. These may, for example, suffer from depression and other psychological complaints.The patients themselves suffer primarily from visual complaints and hearing impairment. In the worst case, this can also lead to complete blindness of the patient. Furthermore, the patients also suffer from heart problems, so that sudden cardiac death can occur. The children are also overweight and suffer from thyroid disorders. Often, Alström’s syndrome also results in short stature and further also in a curved spine. This complaint affects the posture and movement of the affected person. In most cases, the life expectancy of the patient is reduced to about 40 years due to Alström syndrome. A causal therapy is not possible, so that only the complaints can be limited. As a rule, the affected person is thus dependent on regular examinations. Diabetes must also be detected and treated at an early stage.
Prevention
Alström syndrome cannot be prevented because of its genetic cause. Nevertheless, an appropriate lifestyle can mitigate or prevent many symptoms. Light exercise such as swimming, cycling, or running is recommended. If a mutation is already known within the family, genetic counseling should be sought, especially if a child is desired. Under certain circumstances, prenatal diagnostics may be an option.
Follow-up
Because Alström syndrome is a genetic disorder that cannot be treated causally, but only symptomatically, there are usually no special aftercare options available to the affected person. The life expectancy of the patient is also considerably limited and reduced by Alström syndrome, so that most patients die at a young age. Especially the parents and the relatives of the patient are therefore dependent on psychological treatment in Alström syndrome in order to avoid further complications and depressive moods. Contact with other people affected by the syndrome can also prove to be positive and useful, as it can lead to an exchange of information. The affected persons themselves depend on a permanent treatment and on many regular examinations in order to alleviate the symptoms. Mobility can also be increased through various exercises, and these exercises can often be performed in the patient’s own home. In the case of depression in the patient himself, discussions with parents, family or friends are very helpful. In severe cases, Alström syndrome patients depend on external help in their daily lives.
Here’s what you can do yourself
Alström syndrome is a progressively progressive disease that is always associated with severe complications for those affected. Therefore, the most important self-help measure lies in early therapy. Parents of affected children are best advised to talk to their family doctor so that contact can be made with a suitable specialist. The individual symptoms must be treated concomitantly. The increasing blindness, which usually reaches its peak between the tenth and twelfth year of life, must be compensated for by glasses and other aids, and later by organizing a guide dog or comparable assistance measures. Hearing difficulties also require comprehensive treatment, which must be regularly adapted to the progressive course of the disease. If psychological complaints also arise in the context of Alström syndrome, for example depressive moods, anxiety attacks or inferiority complexes, further therapeutic measures are available. The disease can be accepted more easily if there is contact with other affected persons who suffer from the same complaints. The patient requires various operations. Before and after these operations, it is important to follow the doctor’s instructions. Optimally accompanied treatment significantly improves the prospects of a relatively symptom-free life.
