Alström syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 3, 2017
StartDiseasesAlström syndrome

Alström syndrome or Alström's syndrome is an extremely rare genetic disorder affecting approximately 1000 people worldwide. It affects many different organs in the body. It is characterized by obesity, diabetes, blindness, hearing loss, and life-threatening impairment of the kidneys, lungs, and liver. It results from genetic mutations.

Contents

Definition & Facts

According to Alström's Syndrome International, an online resource for patients and families affected by Alström's syndrome, the disease was identified in 1959 by a Swedish physician. It is caused by mutations affecting the ALMS1 gene. It is inherited via an autosomal recessive inheritance pattern. Life expectancy generally does not exceed 50 years of age.

This syndrome can cause multiple organs to fail. It negatively affects the eyes, the ears, kidneys, the liver, the pancreas, the endocrine system, the respiratory system, and the cardiovascular system. The skeletal system is also affected by this condition.

Symptoms & Complaints

Alström's syndrome causes a number of severe, life-threatening symptoms that affect multiple organs in the body. It causes a number of eye and vision problems. It causes dystrophy in the cones by six months of age and by five years of age, it causes destruction of the rods as well. This condition causes light sensitivity, nystagmus, and eventually blindness.

Hearing loss also occurs though there is no standard age at which the hearing loss manifests. Obesity is another symptom of this condition. It may result from overeating. Diabetes mellitus type II is another condition associated with this disorder.

Acanthosis nigricans is a skin condition associated with diabetes and hyperinsulinemia that occurs as well among those with Alström's syndrome. In this condition, dark, velvety, wrinkled patches form on the skin. They typically form on or around skin folds such as those of the armpit and groin.

A number of heart problems occur when one has this syndrome. Congestive heart failure and dilated cardiomyopathy occur in two thirds of all cases of this syndrome. Symptoms of congestive heart failure include edema in the limbs as well as in the lungs (pulmonary edema). Symptoms of dilated cardiomyopathy include shortness of breath and ascites, in which the abdomen swells with fluid.

Alström's syndrome also causes a number of kidney problems. Renal tubular acidosis and end-stage renal disease are two conditions that can ensue among those with this condition. Renal tubular acidosis results in high concentrations of acid in the blood. End-stage renal disease is a condition in which the kidneys cannot function on their own.

The lungs and other organs of the respiratory tract are also affected by this condition. Bronchitis, pulmonary hypertension, acute respiratory distress syndrome, and chronic obstructive pulmonary disorder (COPD) are all respiratory illnesses associated with this condition. Alström's syndrome affects the liver as well, causing cirrhosis and portal hypertension.

Hypogonadism is another symptom. This can manifest among males as having small sex organs while it can result in excessive amounts of androgen among females, manifesting in conditions such as hirsutism and endometriosis. Amenorrhea (that is, the absence of periods) may also occur as a symptom of this condition.

Gingivitis is a possible symptom as are scoliosis and kyphosis. Constipation and abdominal pain may also be symptoms of this disorder. Children born this condition generally do not have intellectual disabilities but typically still do not reach developmental milestones, likely on account of hearing and vision problems.

Causes

Alström's syndrome results from genetic mutations of the ALMS1 gene. It is an autosomal recessive disorder which means that both parents must be genetic carriers of the defective gene to pass the disorder onto to their child. That said, the genetic carriers of this condition do not display symptoms. ALMS1 is a gene that is found in many different types of tissue and codes for thousands of amino acids. Over 100 different types of mutations of ALMS1 are associated with the condition.

Diagnosis & Tests

A medical history, family history, and intake of symptoms will be taken. A physical examination will be performed to examine any deformities.

Eye examinations will be performed. Electroretinography of the cones can reveal minimal activity in the eyes by six months of age. Optic disc drusen will be detected. The macula will appear degraded in an optical coherence tomography, a type of imaging study.

Hearing examinations will be taken to assess the degree and stage of hearing loss. Tests will examine whether or not the person has diabetes. Glucose tolerance tests and fasting plasma glucose tests can help diagnose diabetes and high blood glucose.

Liver function tests may be taken to assess any liver problems. Clinical urine tests will be taken to assess kidney function. Thyroid function tests will also be performed.

A wide array of imaging studies may be pursued to examine the structural and functional abnormalities of the patient. These include computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, ultrasound, and X-ray. Heart function can be assessed with echocardiograms and electrocardiograms.

Treatment & Therapy

The goal of treatment is to improve the quality of life for the person born with this condition which causes so much physical disability. Treating this condition involves a team of specialists as this condition affects so many different organs and organ systems. A kidney transplant as well as pancreas transplant may be necessary. Hormone replacement therapy may help alleviate the symptoms of hypogonadism.

A strict diet as well as the use of metformin may help reduce symptoms among those with hyperinsulinemia and hyperglycemia. Cochlear implants could be used to treat hearing loss associated with this condition. Myringotomy may also be helpful; it is a procedure in which an incision is made into the eardrum and tubes are inserted to relieve pressure and fluid build-up.

Occupational therapy, physical therapy, and speech-language therapy are all employed to help patients with this disorder. Because blindness is so common, children are recommended to begin learning Braille as well as how to navigate the world without sight in anticipation of blindness. The use of mobility aids and assistive devices can be helpful.

Prevention & Prophylaxis

There is no known way to prevent this extremely rare condition because it is a genetic disorder. Prospective parents may undergo genetic counseling in order to assess the risk that any future children may be born with this condition. Genetic testing can help assess whether or not a person is a carrier for the genetic mutations that cause this disorder.