Inherited syndrome with diabetes mellitus; cardiac,
hepatic, and renal involvement; and progressive visual and hearing loss.
First described in 1959 by Carl Henry
Alström, Bertil Hallgren, L.B. Nilsson, and H. Asander, all Swedish
Approximately 200 patients with
Alström syndrome have been reported since the first description in 1959.
The genetic defect of this autosomal recessive inherited disorder has been
mapped to 2p13-p12.
The syndrome results in progressive pigmentary
retinopathy (cone-rod dystrophy) and often cataract. Early loss of central
vision (in contrast to loss of peripheral vision first in retinitis
pigmentosa) results in nystagmus. Light perception usually is lost by age 20
years. Generally mild-to-moderate obesity, advanced bone age, growth
retardation with short stature secondary to growth hormone deficiency, and
sensorineural hearing loss (mild-to-moderate) are additional features.
Alström syndrome can be difficult to diagnose, and noninsulin-dependent
diabetes mellitus developing in late childhood/early adulthood may finally
lead to the diagnosis. Insulin resistance seems to be responsible for the
decreased glucose tolerance and diabetes mellitus. Unresponsiveness of
target organs to the action of other hormones (vasopressin, gonadotropins,
ACTH) has been suspected. Later in life, patients suffer from progressive
chronic nephropathy with renal insufficiency, hepatic failure,
atherosclerosis, and congestive heart failure secondary to dilated
cardiomyopathy (myocardial fibrosis has been demonstrated at autopsy and on
myocardial biopsies, which is not necessarily related to coronary artery
disease). However, an increasing percentage (up to 35%) of patients with
infantile cardiomyopathy has been described in the last years. Adolescent
and adult forms also exist and affect approximately 25% of patients,
usually manifesting between adolescence and age 40 years. Severe pulmonary
interstitial fibrosis with pulmonary hypertension has been reported.
Hypersecretory lungs is a less common finding. Abnormal liver function test
results in early childhood are common. The disease often progresses to
hepatic cirrhosis and hepatic failure in the second or third decade of life.
Other liver findings reported include chronic, nonspecific, lymphocytic
hepatitis; patchy hepatic necrosis; and hepatosplenomegaly with ascites and
portal hypertension. The first signs of renal disease may be polyuria and
polydipsia as a result of a tubular defect secondary to interstitial
fibrosis. Renal biopsy often reveals diffuse glomerulosclerosis, tubular
atrophy, and interstitial fibrosis. End-stage renal disease is a late
finding but often occurs before age 20 years. Urologic problems affect more
than 50% of patients and are characterized by detrusor-urethral
dyssynergia, which may result in lower abdominal and perineal pain. Symptoms
include incontinence, retention, and recurrent urinary tract infections.
Male hypogonadotropic hypogonadism has been described and results in low
plasma testosterone levels secondary to low plasma gonadotropin
concentrations. These males often have small external genitalia and
inadequate secondary sexual development at puberty, often associated with
gynecomastia. Subclinical hypothyroidism has been described. Approximately
one third of Alström syndrome patients have a varying degree of
kyphoscoliosis. Although some patients with mental retardation have been
described, these patients most often are mentally normal.
Patients require extensive workup
before they undergo anesthesia. ...