Alström's Syndrome

Alström's syndrome is a very rare autosomal recessive disorder characterised by progressive cone-rod dystrophy leading to blindness, sensorineural hearing loss, childhood obesity associated with hyperinsulinaemia, and type 2 diabetes mellitus.^[1] The diagnosis should be considered in all patients with infantile cone and rod retinal dystrophy, especially if the weight is above the 90^th centile or if there is infantile cardiomyopathy.

• Dilated cardiomyopathy occurs in approximately 70% of patients during infancy or adolescence.^[2]
• Renal failure, pulmonary, hepatic, and urological dysfunction are often observed, and systemic fibrosis develops with age.^[2]
• The gene map locus for the affected mutated gene (ALMS1) is 2p12-13.^[3]

Epidemiology

• Alström's syndrome is rare; only about 425 people worldwide are known to be affected.^[4]

Presentation

Alström's syndrome in childhood is difficult to recognise without the development of infantile cardiomyopathy and may not be identified until diabetes mellitus develops in the second or third decade.

• Severe progressive infantile retinal dystrophy (visual acuity of 6/60 or less by 10 years of age and no light perception by age 20), with or without nystagmus.
• Deafness.
• Obesity.
• Acanthosis nigricans.
• Cardiomyopathy.
• Nephropathy.
• Alström's syndrome may also be associated with:^[5]
  • Hypothyroidism.
  • Liver dysfunction.
  • Metabolic abnormalities, including hyperuricaemia and elevated serum triglyceride and pre-beta-lipoprotein.^[2]
  • Small penis.
  • Gastrointestinal reflux.

Differential diagnosis^[2]

• Bardet-Biedl syndrome is similar (with retinitis pigmentosa, deafness, obesity and diabetes mellitus) but also includes mental defect, polydactyly or hypogonadism.
• The retinal lesion of Alström's syndrome causes nystagmus and early loss of central vision in contrast to the initial loss of peripheral vision found in other pigmentary retinopathies.

Investigations

• Blood tests for fasting blood glucose, liver function tests, renal function tests, thyroid function tests and triglyceride levels.
• A thorough assessment of vision and ophthalmoscopy by an ophthalmologist.
• Hearing assessment by an ear, nose and throat specialist.
• Assessment of heart function, including echocardiogram.

Management

There is no specific treatment but management will be required for:

• Diabetes.
• Renal impairment.
• Liver dysfunction.
• Visual impairment.
• Deafness.
• Heart failure and other features of cardiomyopathy, eg cardiac arrhythmias.
• Hypothyroidism.

Prognosis

• The prognosis will depend on the progression of glucose intolerance, cardiomyopathy, renal dysfunction and liver impairment.
• Total blindness and deafness are likely to develop.