Format

Send to

Choose Destination

Alström Syndrome.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2003 Feb 7 [updated 2012 May 31].

Author information

1
Consultant Endocrinologist, Torbay Hospital, Torquay, Devon, United Kingdom
2
Consultant Cardiologist, Torbay Hospital, Torquay, Devon, United Kingdom
3
Consultant Urologist, Torbay Hospital, Torquay, Devon, United Kingdom

Excerpt

CLINICAL CHARACTERISTICS:

Alström syndrome is characterized by cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated or restrictive cardiomyopathy, the insulin resistance syndrome, and multiple organ failure. Wide clinical variability is observed among affected individuals, even within the same family. Cone-rod dystrophy presents as progressive visual impairment, photophobia, and nystagmus usually starting between birth and age 15 months. Many individuals lose all perception of light by the end of the second decade, but a minority retain the ability to read large print into the third decade. Children usually have normal birth weight but develop truncal obesity during their first year. Progressive sensorineural hearing loss presents in the first decade in as many as 70% of individuals. Hearing loss may progress to the severe or moderately severe range (40-70 db) by the end of the first to second decade. Insulin resistance is typically accompanied by the skin changes of acanthosis nigricans, and proceeds to type 2 diabetes in the majority by the third decade. Nearly all demonstrate associated dyslipidemia. Other endocrine abnormalities can include hypothyroidism, hypogonadotropic hypogonadism in boys, and polycystic ovaries in girls. More than 60% of individuals with Alström syndrome develop cardiac failure as a result of dilated or restrictive cardiomyopathy. About 50% of individuals have delay in early developmental milestones; intelligence is normal. Liver involvement includes elevation of transaminases, steatosis, hepatosplenomegaly, and steatohepatitis. Portal hypertension and cirrhosis can lead to hepatic encephalopathy and life-threatening esophageal varices. Pulmonary dysfunction and severe renal disease may also develop. End-stage renal disease (ESRD) can occur as early as the late teens.

DIAGNOSIS/TESTING:

The diagnosis of Alström syndrome is based on clinical findings. Molecular genetic testing of ALMS1, the only gene in which mutation is known to cause Alström syndrome, is estimated to detect pathogenic variants in 70%-80% of individuals of northern European descent, and approximately 40% world-wide.

MANAGEMENT:

Treatment of manifestations: Red-tinted prescription lenses for photodysphoria; instruction for the blind or visually impaired; healthy diet and regular exercise; myringotomy tubes and/or hearing aids as needed for hearing impairment; anti-congestive measures as needed for cardiomyopathy; treatment of insulin resistance/type 2 diabetes as in the general population; consider nicotinic acid derivatives for hyperlipidemia; consultation with an endocrinologist if pubertal development and/or menses are abnormal; urinary diversion or self-catherization in those with voiding difficulties; renal transplantation has been successful in a number of cases; appropriate therapy of portal hypertension and esophageal varices; treatment of chronic obstructive pulmonary disease and associated infection per accepted guidelines. Prevention of primary complications: The progression to diabetes mellitus and the severity of hyperglycemia are modifiable by lifestyle and avoidance of severe obesity. Prevention of secondary complications: Routine pediatric immunizations; monitoring of cardiac status and oxygenation during acute illness and postoperatively. Surveillance: Annual assessment of vision and hearing; weight, height, and body mass index; heart (including echocardiography); plasma insulin concentration; lipid profile; plasma ALT, AST, and GGT concentrations; pulmonary function; thyroid function. Every two to three months, fasting plasma glucose concentration; closer follow-up if fasting or postprandial blood glucose concentrations are elevated. Twice-yearly urinalysis and plasma concentrations of electrolytes, uric acid, BUN, and creatinine. Every one to two years, renal and bladder ultrasound examinations if symptomatic and/or if urinalysis is abnormal. Agents/circumstances to avoid: Any substance contraindicated in persons with renal or cardiac failure. Therapy directed at one system may have adverse effects on other systems (ie, dlitazone therapy for diabetes mellitus is contraindicated in the presence of cardiac failure).

GENETIC COUNSELING:

Alström syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants have been identified in an affected family member.

Copyright © 1993-2019, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

Supplemental Content

Support Center