Alstrom syndrome (ALMS), a rare autosomal recessive condition due to mutations in the ALMS1 gene located on the second chromosome, is characterized by progressive multisystem dysfunction in homozygous individuals while heterozygous individuals are asymptomatic [1] [2] [3] [4]. The clinical presentation is variable in onset as well as severity even in individuals belonging to the same family [5].
Symptoms related to different organ systems appear in childhood and progress with age.

• Ocular: Nystagmus and photophobia appear early with complete loss of vision by the second decade of life [6]. Other ocular manifestations include bilateral subcapsular cataracts, optic disc pallor with dystrophy of the cones and rods.

• Otological: Bilateral sensorineural hearing loss starting in childhood or adulthood and progressing to moderate-to-severe hearing loss is noted in a majority of the affected individuals [7] [8]. There may also be episodes of otitis media accompanied by a conductive hearing loss in children [5].

• Endocrine/metabolic: Birth weight of children with ALMS is normal but weight gain starts early in infancy and obesity is a common problem [3] [5]. Hyperinsulinemia with insulin resistance, acanthosis nigricans, and hypertriglyceridemia start developing in childhood or during adolescence, or adulthood [5]. Pancreatitis secondary to severe hypertriglyceridemia has been reported [9] [10]. As a result of metabolic changes, a majority of individuals with ALMS suffer from cardiac and renal impairment and may even present with sudden onset of congestive heart failure. Testicular atrophy and small genitalia have been reported in males while hyperandrogenism and hirsutism with menstrual irregularities and precocious puberty have been reported in females with ALMS [5] [11].

• Liver: Hepatic dysfunction is noticed as an asymptomatic increase in the levels of serum transaminases, followed by hepatosplenomegaly, a possible presence of hepatocellular adenoma [12], and the progression to cirrhosis and its sequelae.

• Renal: Progressive polyuria, renal tubular acidosis with hypertension, urinary tract infections, obstructive uropathy and instability of detrusor muscle can occur leading to end-stage renal disease (ESRD) in adolescence [5] [13].

• Respiratory: Recurrent respiratory tract infections result in problems ranging from chronic rhinosinusitis to chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS).

• Neurological: Affected individuals have normal intelligence with delayed motor and intellectual milestones, balance changes [14] [15], speech problems and cerebellar anomalies [16].

Although growth spurt is normal in early childhood, it plateaus off and individuals with ALMS usually have a short stature, round face, thick ears, frontal alopecia, abnormal and discolored dentition, scoliosis, flat feet and short, fat fingers and toes.

Mortality in young ALMS patients is due to dilated cardiomyopathy while in older patients is mainly due to renal failure [5] [17].

The diagnosis of ALMS is based on the typical clinical presentation, although, occasionally variable phenotypic expression can delay the diagnosis [2] [3]. Cone electroretinography reveals weak cone activity in infancy with severely diminished responses and cone dystrophy on full-field electroretinography by 3 years of age. Optical coherence tomography (OCT) imaging has been used to demonstrate macular thinning and developmental arrest [18]. Laboratory tests help to detect elevated blood sugar levels with hypertriglyceridemia, elevated hepatic transaminases, abnormal renal function tests, albuminuria, low levels of testosterone, elevated gonadotropins, low levels of growth hormone, abnormal levels of insulin-like growth factors [19] [20], elevated leptin levels [20], and secondary or subclinical hypothyroidism.

Molecular genetic analysis is used to confirm the diagnosis [21] [22] [23].

There is currently no cure for Alström Syndrome, and treatment focuses on managing the symptoms and preventing complications. Regular monitoring by a multidisciplinary team of specialists is essential. Vision and hearing aids can help manage sensory impairments. Lifestyle modifications, including a healthy diet and regular exercise, are recommended to manage obesity and diabetes. Medications may be prescribed to control blood sugar levels, blood pressure, and heart function. Early intervention and supportive therapies can improve quality of life.

The prognosis for individuals with Alström Syndrome varies depending on the severity of symptoms and the effectiveness of management strategies. While the condition is progressive and can lead to significant health challenges, early diagnosis and comprehensive care can improve outcomes. Life expectancy may be reduced due to complications such as heart disease and organ failure, but many individuals live into adulthood with appropriate medical care.

Alström Syndrome is caused by mutations in the ALMS1 gene, which provides instructions for making a protein involved in various cellular processes. The exact function of this protein is not fully understood, but it is believed to play a role in cilia function, which are hair-like structures on the surface of cells that are important for cell signaling and movement. The disorder is inherited in an autosomal recessive manner, meaning a person must inherit two copies of the mutated gene, one from each parent, to develop the condition.

Alström Syndrome is an extremely rare condition, with an estimated prevalence of less than 1 in 1,000,000 people worldwide. It affects both males and females equally and has been reported in various ethnic groups. Due to its rarity, the syndrome is often underdiagnosed or misdiagnosed, which can delay appropriate management and care.

The pathophysiology of Alström Syndrome is linked to the dysfunction of cilia, which are essential for various cellular functions. Mutations in the ALMS1 gene disrupt the normal function of cilia, leading to the wide range of symptoms observed in the syndrome. The impaired ciliary function affects multiple organ systems, contributing to the progressive nature of the disease and the development of complications such as vision and hearing loss, metabolic disorders, and organ dysfunction.

As a genetic disorder, there is no known way to prevent Alström Syndrome. Genetic counseling is recommended for families with a history of the condition to understand the risks and implications of passing the mutated gene to offspring. Prenatal testing and preimplantation genetic diagnosis may be options for at-risk couples to consider.

Alström Syndrome is a rare genetic disorder characterized by a range of symptoms affecting multiple organ systems. It is caused by mutations in the ALMS1 gene and is inherited in an autosomal recessive pattern. While there is no cure, early diagnosis and comprehensive management can improve quality of life and outcomes for affected individuals. The condition requires a multidisciplinary approach to care, with regular monitoring and supportive therapies to address the various symptoms and prevent complications.

For patients and families affected by Alström Syndrome, understanding the condition and its implications is crucial. It is important to work closely with a team of healthcare providers to manage symptoms and maintain overall health. Regular check-ups and monitoring can help detect and address complications early. Support groups and resources are available to connect with others facing similar challenges and to provide additional information and support.

1. Alström CH, Hallgren B, Nilsson LB, Åsander H. Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness. A specific syndrome (not hitherto described) distinct from Laurence-Moon-Biedl syndrome. A clinical endocrinological and genetic examination based on a large pedigree. Acta Psychiatr. Neurol. Scand. Suppl. 1959;129:1–35.
2. Marshall JD, Paisey RB, Carey CM, MacDermott S. In: Gene Reviews [Internet], Seattle (WA): University of Washington, Seattle; 1993-2003. Pagon RA, Bird TC, Dolan CR, Stephens K, editors. 2010.
3. Marshall JD, Beck S, Maffei P, Naggert JK. Alström Syndrome. Eur. J. Hum. Genet. 2007;15:1193–1202.
4. Marshall JD, Ludman MD, Shea SE, et al. Genealogy, natural history, and phenotypic features of Alström syndrome in a large Acadian kindred and three unrelated families. Am. J. Med. Genet. 1997;73:150–161.
5. Marshall JD, Bronson RT, Collin GB, et al. New Alström Syndrome phenotypes based on the evaluation of 182 cases. Arch. Intern. Med. 2005;165:675–683.
6. Russell-Eggitt IM, Clayton PT, Coffey R, et al. Alström syndrome. Report of 22 cases and literature review. Ophthalmol. 1998;105:1274–1280.
7. Welsh LW. Alström syndrome: Progressive deafness and blindness. Ann. Otol. Rhinol. Laryngol. 2007;116:281–285.
8. Paisey RB, Carey CM, Parkinson MJ, et al. Alström syndrome-the case for secondary prevention. Diabet. Res. Clin. Pract. 2000;50 (Suppl. 1): S202.
9. Paisey RB, Carey CM, Bower L, et al. Hypertriglyceridaemia in Alstrom's syndrome: causes and associations in 37 cases. Clin. Endocrinol. 2004;60:228–231.
10. Wu WC, Chen SC, Dia CY, et al. Alström syndrome with acute pancreatitis: A case report. Kaohsiung J. Med. Sci. 2003;19:358–361.
11. Kocova M, Sukarova-Angelovska E, Kacarska R, et al. The unique combination of dermatological and ocular phenotypes in Alstrom syndrome; severe presentation, early onset and two novel ALMS1 mutations. Br. J. Dermatol. 2011; 164 (4): 878-880.
12. Morgan J, Sadler MA, Siegel S. US, CT, and MR imaging of hepatic masses in Alström syndrome: a case report. Clin. Imaging. 2008;32:393–395.
13. Charles SJ, Moore AT, Yates JRW, Green T, Clark P. Alstrom's syndrome: further evidence of autosomal recessive inheritance and endocrinological dysfunction. J. Med. Genet. 1990;27:590–592.
14. Marshall JD, Maffei P, Collin GB,Naggert JK. Alstrom Syndrom: genetics and clinical overview. Curr Genomics. 2011;12(3): 225-235.
15. Möller C. Vestibular testing in children. In: Newton W, editor. Pediatric Audiological Medicine. Wiley- Blackwell; 2009.
16. Yilmaz C, Çaksen H, Yilmaz N, et al. Alstrom Syndrome associated with cerebral involvement: An unusual presentation. Eur. J. Gen. Med. 2006;3:32–34.
17. Minton JA, Owen KR, Ricketts CJ, et al. Syndromic obesity and diabetes: changes in body composition with age and mutation analysis of ALMS1 in 12 United Kingdom kindreds with Alstrom syndrome. The Journal of clinical endocrinology and metabolism. 2006;91:3110–3116.
18. Vingolo EM, Salvatore S, Grenga PL, et al. High-resolution spectral domain optical coherence tomography images of Alström syndrome. J. Pediatr. Ophthalmol. Strabis. 2010;47:e1–3.
19. Maffei P, Munno V, Marshall JD, et al. GH and IGF-I Axis in Alström Syndrome. J. Endocrinol. Invest. 2000;23(Suppl. 6):29.
20. Maffei P, Boschetti M, Marshall JD, et al. Characterization of the IGF system in 15 patients with Alström syndrome. Clin. Endocrinol. 2007;66:269–275.
21. Collin GB, Marshall JD, Ikeda A, et al. Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome. Nat. Genet. 2002;31:74–78.
22. Hearn T, Renforth GL, Spalluto C, et al. Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome. Nat. Genet. 2002;31:79–83.
23. Marshall JD, Hinman EG, Collin GB, et al. Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Hum. Mutat. 2007;28:1114–1123.