Alstrom syndrome is a rare autosomal recessive disorder characterized by cone-rod dystrophy with secondary nystagmus and photodysphoria, truncal obesity, progressive bilateral sensorineural hearing loss, dilated or restrictive cardiomyopathy, insulin resistance syndrome, and multiple organ failure. Acanthosis nigricans, a skin disorder characterized by dark, velvety skin in body folds and creases, is usually seen in patients. The first manifestations of this condition can appear as early as from birth to 15 months. With increasing age, the range of manifestations increases, till it encompasses multiple organ failure, involving the liver, kidneys, bladder, and lungs. More than 60% of patients with this condition eventually develop cardiac failure due to dilated or restrictive cardiomyopathy. Alstrom syndrome is extremely rare, with only about 500 cases being discovered worldwide. The reported patients have a predominance of English kindreds.
Alstrom syndrome is diagnosed based on its clinical features. Differential diagnoses include Laurence-Moon or Bardet-Bieldl syndromes. Molecular diagnosis is technically feasible for this condition. In approximately 70-80% of patients of Northern European descent, and about 40% of patients worldwide, genetic testing can detect causal mutations. The life span of patients with this condition rarely exceeds the age of 40-years. There is no specific therapy for Alstrom syndrome. However, early diagnosis and intervention may moderate the progression of the disease and may improve the length and quality of the patient's life. These interventions include diabetes and cardiac medications, the use of hearing aids, and thyroid hormone replacement.
Alstrom syndrome is transmitted in an autosomal recessive manner. Mutations in ALMS1 gene are known to cause this condition. The exact function of the ALMS1 protein is not known. However, it has been shown to express ubiquitously in almost all tissue types and localize subcellularly. It has been proposed that ALMS1 may be involved in the functioning of centrosomes or basal bodies.
A study by Macari et al. (1998) that involved a consanguineous family of North African origin with three affected sibs, managed to narrow down the chromosomal region linked to Alstrom syndrome to an interval of 6.1-cM from a previously established larger interval of 14.9-cM on chromosome 2p13-12.
Farah et al. (1996) described a Bedouin brother and sister with Alstrom's syndrome, the pair presented with classical features of the disorder (obesity, diabetes mellitus, early loss of central vision, retinitis pigmentosa and sensorineural deafness). The sister, however, suffered from recurrent attacks of focal dystonia mainly affecting the lower limbs. The association between the latter feature and Alstrom's syndrome has not been reported before but it could simply be a coincidence. On the other hand, renal calculi and salt wasting nephropathy where detected in the brother.
[Farah S, Shubaili AF, Khuraibit A, Sabry MA, Farag TI. Phenotypic variability of Alstrom's Syndrome in Bedouin sibs. Med Princ Pract. 1996; 5(2):118-20.]
Aldahmesh et al. (2009) reported four novel alleles in the ALMS1 gene in consanguineous families with Alström disease. They commented on the interesting observation of allelic heterogeneity for a very rare autosomal recessive disorder in a highly inbred population.
Safieh et al., (2016) described a 5-year old Saudi girl with nystagmus and slight photophobia. The fundus examination revealed a peppery mottling of the fundus. The discs were flat with optic atrophy and attenuated arterioles in both eyes. She had short stubby fingers tapering at the distal phalanges. Examination at 12-years of age revealed mild mid-facial hypoplasia, bilateral enophthalmos, and diabetes. She was wearing hearing aids. Mutation screening of candidates genes and testing revealed a pathogenic mutation in the ALMS1 gene. Authors concluded that this mutation expanded the genotypic spectrum of congenital retinal dystrophies in the Saudi population.