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At a glance

Inherited syndrome with progressive loss of vision and hearing, diabetes mellitus, cardiac, hepatic, and renal involvement.

Synonym

Alström-Hallgren Syndrome.

History

First described in 1959 by the Swedish physicians Carl Henry Alström, Bertil Hallgren, L.B. Nilsson, and H. Asander.

Incidence

Approximately 700 patients with Alström Syndrome have been reported since the first description in 1959 with an estimated prevalence of 1-9 in 1,000,000.

Genetic inheritance

This autosomal recessive inherited disorder is caused by mutations in the ALMS1 gene, which has been mapped to chromosome 2p13-p12. ALMS1 is a protein located in centrosomes and basal bodies of primary cilia. Its biological functions are still being elucidated, but include involvement in ciliary function and structural maintenance, intracellular trafficking, regulation of ciliary signaling pathways, cell cycle control, and cellular differentiation. Alström Syndrome is therefore considered as ciliopathy.

Diagnosis

Based on the typical, progressive clinical features developing already in the first decade of life.

Clinical aspects

There is a wide variability in the severity and the time of onset of symptoms, even among patients with identical mutations within the same family. The syndrome is characterized by cone-rod-dystrophy, progressive sensorineural hearing loss, insulin-resistance with diabetes mellitus Type II, hyperinsulinemia and truncal obesity, and multiple organ failures (eg, dilated or restrictive cardiomyopathy, hepato-, nephro-, pneumo-, and endocrinopathy). The cone-rod dystrophy presents as progressive pigmentary degeneration of the retina (with mottling and patchy atrophy of the retinal pigment epithelium and characteristically absent intraretinal pigment migration) with early loss of central vision (in contrast to initially peripheral vision loss in retinitis pigmentosa) and results in nystagmus and photophobia that usually starts in the first 15 months of life. An electroretinogram is used to confirm the cone-rod dysfunction. While some patients preserve some vision until the end of the third decade of life, most have lost their perception to light by the end of the second decade of life. Hyperopia, bull’s eye maculopathy, subcapsular cataracts, and visual field constriction have also been reported. About two-thirds of patients present with sensorineural hearing loss in the first decade of life and may progress to the severe hearing impairment by the age of 20 years. Birth weight is usually normal, but mild-to-moderate truncal obesity already develops in the first year of life. The diagnosis of Alström Syndrome is not always straightforward and often the non–insulin-dependent diabetes mellitus developing in late childhood/early adulthood may finally point to the right diagnosis. Diabetes mellitus Type II is often accompanied by acanthosis nigricans, hyperpigmented areas typically affecting intertriginous skin. Growth retardation with short stature is due to growth hormone deficiency. Approximately one-third has kyphoscoliosis of varying degree. Advanced bone age has been reported. Dyslipidemia with hypertriglyceridemia and most often normal cholesterol levels is common. Hypertriglyceridemia ...

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