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 diagnosis²

• 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.