Introduction:
Alstrom syndrome is a single-gene disorder that affects one in every one million individuals. It was first described in 1959 by Swedish psychiatrist Carl-Henry Alström. Therefore this disease is named after him.
What Is Alstrom Syndrome?
Alstrom syndrome is a severe inherited disorder that affects the body systems like the heart, kidneys, eyes, ears, lungs, and other endocrine hormones. A few symptoms of Alstrom syndrome usually develop in infancy and increase gradually till adulthood.
What Causes Alstrom Syndrome?
The main causing factor is the defects (mutation) in the ALMS1 gene. This gene is responsible for the specific proteins present in cells of multiple organs. Any changes in the ALMS1 gene affect various systems of the body. If the mother and father carry the same abnormal gene, the child is more prone to get the defective gene which develops the genetic disorder. It mainly occurs due to marriages among relatives.
What Are the Clinical Features of Alstrom Syndrome?
Various signs and symptoms of Alstrom syndrome vary in different patients. Not all the symptoms that are listed below are present in every patient.
1) Loss of Vision: The cone cells of the eyes are responsible for color vision, and rod cells for night vision define the size and shape of the object we see. The damage of these cells (cone-rod dystrophy) occurs during the initial few months after birth in Alstrom syndrome, leading to low vision, increased sensitivity to light (photophobia), rapid and uncontrolled movement of eyes (nystagmus), and clouding of the lenses (cataract) of the eyes also occurs. By the age of 12 to 16, complete vision loss or blindness occurs.
2) Heart Disease: The heart muscles get enlarged and weakened (dilated cardiomyopathy), and their pumping ability declines. It develops at an early age, and the children may have a cough, fatigue, shortness of breath, abdominal pain, etc. if heart failure occurs.
3) Hearing Loss: The inability of the ear's nerves to transmit signals to the brain occurs, leading to sensorineural hearing loss, which may affect both ears. The central part of the ear gets filled with fluid (glue ear), which also causes hearing loss in children. Otitis media (infection in the middle ear) is also seen.
4) Obesity: The birth weight is average; however, excessive eating due to increased hunger (polyphagia) leads to obesity in early adolescence. The fat mainly accumulates in the chest and abdomen (truncal obesity), sparring the legs and arms.
5) Hormonal Disturbances:
- The children may develop type 2 diabetes mellitus due to resistance to insulin and increased blood glucose level. They have symptoms like increased thirst (polydipsia), increased hunger, and increased urination (polyuria).
- Disturbances in the growth hormone leading to short stature in children aged 14 years to 16 years are observed. Delays in milestones are seen in infants, like crawling and walking, and language learning is delayed in toddlers. But the intelligence level of the kids is average.
- In males, low hormones are produced by testes that cause a delay in puberty, and enlarged breasts are observed. In females, polycystic ovarian disease may develop.
- Decreased production of thyroid hormone leads to hypothyroidism.
6) Kidney Disease: Dysfunctioning kidneys cause swelling of ankles and feet, which may worsen kidney failure during adolescence. Urinary abnormalities like difficulty in beginning urine, inability to control urine, and recurrent urinary infections are other symptoms.
7) Lung Manifestations like frequent colds, dry cough, sinusitis, wheezing, etc.
8) Liver Disorders: Fat accumulation (fatty liver) and scarring in the liver eventually cause liver dysfunction.
9) Hyperlipidemia or increase in the level of triglycerides.
10) Skin Conditions like acanthosis nigricans are seen in a few patients. It causes darkish discoloration of the armpits, neck, groin, etc.
11) Other Neurological Disturbances like seizures, disorders in the coordination of muscular activities, and muscle pain are reported in a few patients.
What Is the Differential Diagnosis of Alstrom Syndrome?
The diseases that possess similar symptoms which lead to misdiagnosis are as follows:
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Bardet–Biedl Syndrome (BBS) is a genetic disorder characterized by rod and cones dystrophy, hormonal abnormalities, truncal obesity, and kidney disorders similar to Alstrom syndrome.
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Leber Congenital Amaurosis (LCA) is a rare genetic disorder in which vision is lost at birth or a few years after birth. Cataracts, photophobia, hearing loss, and intellectual disability also occur.
How to Diagnose Alstrom Syndrome?
The diagnostic methods are done to evaluate the characteristic features of Alstrom syndrome.
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A physical examination of the patient and detailed medical history and family history is done to identify any abnormalities in the heart, kidney, liver, and other hormones. Height and weight assessments are also done.
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Eye examination: An ophthalmologist makes special eye tests to detect any defects in the retina.
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Electroretinogram (ERG) measures the response of rods and cones of the eye to light.
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Optical coherence tomography (OCT) is a test done to detect any abnormalities in the retina.
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Color vision testing identifies if the patient can distinguish different colors.
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Ultrasound scan of the kidney to identify the abnormalities.
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An audiometry test is done to detect the intensity of hearing loss.
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Other diagnostic methods include a blood test to determine glucose, triglycerides, and hormone levels.
How to Treat Alstrom Syndrome?
No specific treatment is available; however, adequate measures are taken to reduce symptoms and improve quality of life.
Supportive Therapy:
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Training such as voice recognition, tools, and systems usage to read and write is given before the vision is completely lost.
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Hearing aids that help to improve hearing and speech are used. A cochlear implant is a device that partially restores hearing.
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Patients are advised to maintain a good diet, reduce weight and do physical exercise like walking.
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Prenatal counseling is given to parents with Alstrom syndrome regarding the risk.
Pharmacological Therapy:
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ACE inhibitors are suggested to lower blood pressure.
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Digoxin and other drugs help produce a normal heartbeat.
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Diuretic drugs are advised to increase urine output and decrease fluid retention in the body. Kidney transplantation is also helpful in case of severe kidney failure.
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Hormone replacement therapy with L-thyroxine, testosterone, and estrogen helps manage hypothyroidism and other endocrine disorders (irregular menses).
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Insulin medications, diet modifications, and regular exercise maintain normal blood glucose levels.
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PBI-4050 is a drug that is under study. Researchers have found this drug to be safe and helpful in reducing scarring in the heart and lungs and normalizing blood glucose levels.
Conclusion:
It is challenging for patients to deal with Alstrom syndrome. However, early diagnosis of the disease and coordinated efforts by multispecialty doctors in treating the syndrome can improve the patient's quality of life.
