Alström syndrome

Classification according to ICD-10
Q87.8	Other specified congenital malformation syndromes, not elsewhere classified - Alström syndrome
ICD-10 online (WHO version 2019)

The Alström syndrome is a rare autosomal recessive genetic disease . The disease exhibits complex and variable symptoms of many of the body's organ systems, which increase with age. All patients develop photophobia and nystagmus in early childhood . The visual impairment is progressive and children usually go blind by the age of 12. Other disorders affect the metabolism , the endocrine system and the vital organs kidneys , liver and heart . The cognitive performance is not or only very slightly restricted, which distinguishes the Alström syndrome from the Bardet-Biedel syndrome , as the sub-form of which it was regarded until the early 1980s.

The disease was named after Carl Henry Alström , who first described it in Sweden .

root cause

The cause of Alström syndrome is not yet fully understood. The disease is triggered by mutations in the ALMS1 gene, which is located on chromosome 2p31. The gene codes for a large protein that can be found in almost all cells of the body in the centrosome . Therefore, the disease belongs to the group of ciliopathies .

Frequency and epidemiology

Alström syndrome is difficult to diagnose; On the one hand it is very rare and therefore unknown to most doctors, on the other hand it shows complex and variable symptoms that only develop over time. In many patients, the diagnosis is therefore only made in adolescence or adulthood. Alström syndrome occurs all over the world, in all countries and ethnic groups. In the 1990s, the articles were initially used for 20 and then 60 patients worldwide, but the disease (as of 2008) has been diagnosed in over 500 people in over 45 countries. However, there are certainly many more patients for whom the diagnosis has simply not yet been made.

diagnosis

The diagnosis is made based on the symptom constellation and can be supplemented by a genetic test. However, the genetic test can only confirm the disease in about half of all cases (as of 2008), so a negative test result does not rule out the disease.

Symptoms

Photophobia and nystagmus usually begin at birth or shortly afterwards, the visual impairment is progressive and the children go blind by the age of 12. Hearing damage also begins during childhood. Dilated cardiomyopathy and sudden heart failure can occur in childhood, adolescence, or adulthood. The risk of cardiomyopathy in adolescence or adulthood is increased for patients who have had dilated cardiomyopathy in infancy. Other common problems are obesity, insulin resistance or type 2 diabetes , dark skin (called acanthosis nigricans), high levels of fat - especially triglycerides  - in the blood, liver problems, infertility and thyroid problems. Other symptoms include thin hair, short stature, and scoliosis . The following table provides an overview, with information in brackets on the frequency and mean age of the onset of symptoms:

• Nystagmus (100%, 6 months)
• Photophobia (100%, 6 months)
• Visual acuity reduction (100%, 1 year)
• Blindness (100%, 13 years)
• Chronic otitis media (40%, 2 years)
• Sensoneural hearing loss (88%, 6 years)
• Passenger dilated cardiomyopathy (42%, 6 months)
• Recurrence of cardiomyopathy (13%, 15 years)
• First manifestation of cardiomyopathy in adolescence or adulthood (18%, 25 years)
• Overweight (98%, 4 years)
• Short stature below the 50th percentile (98%, 13 years)
• Hyperinsulinism (92%, 16 years old)
• Type 2 diabetes mellitus (68%, 20 years)
• Hypertriglyceridemia (52%, 21 years old)
• Hypothyroidism (17%, 20 years)
• Male hypogonadism (78%, 12 years old)
• Disorders of the female sex hormone balance (52%, 18 years)
• Gastrointestinal complaints, including gastroesophageal reflux (33%, 15 years)
• Elevated liver enzymes (92%, 10 years)
• Fatty liver (23%, 14 years)
• Portal vein hypertension (9%, 18 years old)
• Urinary tract infections (19%, 15 years)
• Bladder Dysfunction (48%, 14 Years)
• Kidney disease (49%, 15 years)
• High blood pressure (30%, 14 years)
• Lung problems (52%, 2 years)
• Asthma (19%, 5 years)
• Chronic bronchitis (24%, 10 years)
• Sleep disorders (15%, 9 years)
• Muscle weakness (29%, 13 years)
• Absence seizures (12%, 9 years)
• Changed sleep pattern (13%, 14 years)
• Developmental Delay (46%, 3 Years)
• Delay in the development of fine motor skills (21%, 2 years)
• Delayed language acquisition (11%, 4 years)
• Delayed cognitive performance (16%, 6 years)
• Autism spectrum disorder (8%, 10 years)

therapy

There is no causal therapy for Alström syndrome. Many of the symptoms can be alleviated through therapeutic measures or avoided through a preventive lifestyle. Regular patient care in a center is therefore of paramount importance. The examinations to be carried out regularly include heart echo examinations, blood samples, blood pressure measurements and measures to reduce weight or avoid obesity. Marshall et al. (2007) have published an overview of individually useful studies. Organ transplants have already been carried out in Alström patients (kidney, heart). Since it is a multi-organ disease, the transplantation of an organ for Alström patients is seen as controversial.

literature

• Jan D. Marshall et al. a .: Alstrom Syndrome (Practical Genetics) . In: Eur J Hu Genet , 15, 2007, pp. 1193–1202, nature.com (PDF; 142 kB).

Web links

• GeneReviews
• Alström syndrome. In: Orphanet (Rare Disease Database).
• Self-help group Alstrom Syndrome International (ASI)
• German-language site ASI

Individual evidence

1. ↑ Carl Henry Alström et al. a .: Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness. A specific syndrome (not previously described) distinct from Laurence-Moon-Biedl syndrome. A clinical endocrinological and genetic examination based on a large pedigree . In: Acta Psychiatr Neurol Scand 34 (Suppl. 129), 1959, pp. 1-35.
2. ↑ Gayle B. Collin et al. a .: Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome . In: Nat Genet . 31, 2002 pp. 74-78, PMID 11941369 .
3. ↑ Tom Hearn et al. a .: Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome . In: Nat Genet. 31, 2002 pp. 79-83, PMID 11941370 .
4. ↑ Tom Hearn et al. a .: Subcellular localization of ALMS1 supports involvement of centrosome and basal body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes. In: Diabetes 54, 2005, pp. 1581-1587. diabetesjournals.org
5. ↑ JL Badano u. a .: The ciliopathies: an emerging class of human genetic disorders . In: Annu Rev Genomics Hum Genet . 7, 2006, pp. 125-148, PMID 16722803 .
6. ↑ Jan D. Marshall et al. a .: Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome . In: Hum Mutat. 28, 2007, pp. 1114-1123, PMID 17594715 .
7. ↑ Jan D. Marshall et al. a .: New Alström syndrome phenotypes based on the evaluation of 182 cases. In: Arch Intern Med . 165, 2005, pp. 675-683. ama-assn.org
8. ↑ Jan D. Marshall et al. a .: Alstrom Syndrome . In: Eur J Hu Genet (Practical Genetics) 15, 2007, pp. 1193-1202, nature.com (PDF; 142 kB).

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !