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].

• Short Stature

  It may be associated with acanthosis nigricans, hypergonadotropic hypogonadism, hepatic dysfunction, hepatic steatosis, hyperlipidaemia, dilated cardiomyopathy and short stature. [ncbi.nlm.nih.gov]

• Disability

  One of the best ways to save yourself a lot of headaches over your Social Security Disability claim is to have a professional Social Security Disability lawyer handle your claim for you. [disabilitybenefitscenter.org]

  The disability of other organs is considered, namely, the kidney, the heart, and the metabolic and endocrine systems. [ncbi.nlm.nih.gov]

  Hoppa till innehåll Disability and quality of life in individuals with postpolio syndrome. 2000 (Engelska)Ingår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 22, nr 9, s. 416-422Artikel i tidskrift (Refereegranskat) Published [diva-portal.se]

• Asymptomatic

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

  Heterozygotes (carriers) are asymptomatic. Sibs of a proband At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. [ncbi.nlm.nih.gov]

  In many individuals, early kidney dysfunction may not cause symptoms (asymptomatic). Two common signs of kidney disease are excessive urination (polyuria) and excessive thirst (polydipsia). [rarediseases.org]

• Nausea

  Here’s 11 Ways to Cope Nausea and Birth Control Pills: Why It Happens and How to Prevent It The Difference Between VLDL and LDL 5 Recipes That’ll Help Fuel Your Winter Outdoor Adventures Bleeding After Hysterectomy: What to Expect Unexplained Bruising [healthline.com]

  Side effects may include nausea. Exenatide (Byetta®) is a synthetic form of exendin-4, a substance that naturally occurs in the body and helps increase insulin secretion from the pancreas. [naturallivingcenter.net]

• Vomiting

  Pancreatitis can be associated with abdominal pain, chills, jaundice, weakness, sweating, vomiting, and weight loss. Some males with Alström syndrome may experience diminished hormone production by the testes (hypogonadotrophic hypogonadism). [rarediseases.org]

• Heart Failure

  Idiopathic dilated cardiomyopathy is a heritable, genetically heterogeneous disorder characterized by progressive heart failure. [ncbi.nlm.nih.gov]

  Minor criteria Obesity and/or insulin resistance and/or Type 2 Diabetes History of dilated cardiomyopathy with congestive heart failure. [medcaretips.com]

  Multiple organ systems later can be affected, resulting in blindness, hearing impairment, type 2 diabetes, heart failure, liver disease, urological dysfunction, pulmonary fibrosis, and renal failure. [medicinenet.com]

• Discolored Enamel

  In both cases, gingivitis was present and also light yellow-brown discolored enamel bands were observed on the anterior teeth. This staining may have resulted from discoloration of the preexisting slight band-like enamel hypoplasia. [ncbi.nlm.nih.gov]

  In both cases, gingivitis was present and also light yellowbrown discolored enamel bands were observed on the anterior teeth. This staining may have resulted from discoloration of the preexisting slight band-like enamel hypoplasia. [jlc.jst.go.jp]

• Visual Impairment

  The ophthalmologic findings for both brothers revealed infantile-onset severe retinal degeneration and visual impairment, marked macular thinning, and severe cataracts. [ncbi.nlm.nih.gov]

  […] these symptoms Severe Visual Impairment Hearing loss Heart problems Excessive weight gain Not everyone with Alstrom Syndrome will experience all of these symptoms Cone Rod Dystrophy Sensorineural Hearing Loss Dilated Cardiomyopathy Obesity Child 4-10 [geneticdisordersuk.org]

  Renal impairment. Liver dysfunction. Visual impairment. Deafness. Heart failure and other features of cardiomyopathy, eg cardiac arrhythmias. Hypothyroidism. [patient.info]

  Financial Services Advocacy Deaf/Hard of Hearing Diabetes Family Support Heart Disease/Defects Research Visually Impaired / Blind Counties Serviced Nationwide International ABOUT SPECIAL KIDS RESOURCE DIRECTORY 7172 Graham Road, Suite 100, Indianapolis [aboutspecialkids.org]

• Hearing Impairment

  The patient had underlying cone-rod dystrophy of the retinas, nystagmus, obesity, progressive sensorineural hearing impairment, diabetes mellitus, and hypertriglyceridemia, compatible with the clinical diagnosis of Alström syndrome. [ncbi.nlm.nih.gov]

• Advanced Bone Age

  The advanced bone age and normal early growth may be due to hyperinsulinism. [ncbi.nlm.nih.gov]

  Alström Syndrome Further features identified: Congestive heart failure secondary to cardiomyopathy Sensorineural hearing loss Short stature / advanced bone age / scolosis Progressive, chronic nephropathy Liver fibrosis 19. [slideshare.net]

  (DCM), T2DM, normal intelligence (but delay of developmental milestones), absence of digital anomalies, and advanced bone age with reduced final adult height can be helpful in distinguishing this syndrome from closely related disorders. [5] There is, [ijem.in]

• Alopecia

  We report a case of a 20 -year-old caucasian male with hearing and visual loss, short stature, insulin resistant diabetes, dilated cardiomyopathy, hepatic and renal dysfunction, hypertension, and alopecia. [ncbi.nlm.nih.gov]

  On examination, she was found to have alopecia, hirsutism, acanthosis, and large sweaty hands. Investigations revealed transaminitis (sixfold high enzymes), high blood sugars, and high serum triglyceride level. [ijem.in]

  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 [symptoma.com]

  […] growth hormone, which may result in short stature in adulthood; high blood pressure (hypertension), abnormally decreased activity of the thyroid gland and underproduction of thyroid hormones (hypothyroidism), advanced bone age; patchy areas of hair loss (alopecia [rarediseases.org]

• Kidney Failure

  The treatment for renal (kidney) failure depends on how well the kidneys are working, but dialysis and kidney transplants are available should they fail completely. [diabetes.org.uk]

  Renal dysfunction: Lifestyle changes and, if necessary, blood pressure and diabetes medications, can help to reduce the risk of kidney failure. If kidney failure develops, kidney transplantation may be advised. [diabetes.co.uk]

  Description Alstrom Syndrome is a very rare genetic condition which leads to progressive blindness and deafness and can also lead to heart and kidney failure, diabetes, liver dysfunction and associated problems. [sightlinedirectory.org.uk]

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].

He developed impaired glucose tolerance at 6 years of age and treatment with metformin was initiated. After 8 months of treatment with metformin he developed DM2. The dose of metformin was increased, and rosiglitazone added. [ncbi.nlm.nih.gov]

Although there is no specific treatment for this condition, there are treatments to manage many of the symptoms. [diseaseinfosearch.org]

Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions . [patient.info]

The only current treatment options include management of the symptoms. Following 24 weeks of treatment with PBI-450, data for 9 is now available showing the drug can reduce kidney damage. [raredr.com]

Sustained safety observed over 48 weeks of treatment Beneficial clinical effects in liver sustained over 48 weeks of treatment Positive results support requests for meetings with both FDA and EMA to define the clinical-regulatory pathway for approval [prnewswire.com]

The prognosis regarding survival is correlated with the severity of renal failure. [ncbi.nlm.nih.gov]

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. [patient.info]

Diagnosis - Alström syndrome Prognosis - Alström syndrome A prognosis for Alström syndrome is complicated because it widely varies. Any person that has the syndrome have different set of disorders. [checkorphan.org]

Previous comprehensive testing of blood, urine, and skin biopsy specimen was negative for metabolic, mitochondrial, storage, and infectious etiologies. Ophthalmologic examination was normal. [ncbi.nlm.nih.gov]

Patient 2 was diagnosed with sensorineural hearing loss of unknown genetic etiology, as was his older brother. Cochlear function at age 6 was tested, and was abnormal. [bjorl.org]

Etiology AS is caused by mutations in the ALMS1 gene (2p13.1). Its molecular function is currently unknown, although roles in ciliary function, cell cycle control, and intracellular transport have been suggested. [orpha.net]

[…] 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 [patient.info]

The epidemiology of oral human papillomavirus infection in healthy populations: A systematic review and meta-analysis. Oral Oncol 82:91-99, 2018. e-Pub 2018. PMID: 29909908. [faculty.mdanderson.org]

Summary Epidemiology Prevalence is unknown. Approximately 950 cases have been identified worldwide. Clinical description The clinical features, age of onset, and severity can vary greatly among and within families. [orpha.net]

Alström syndrome is being studied as a model which would potentially shed light on the pathophysiology of diabetes mellitus. [ncbi.nlm.nih.gov]

However, new obstacles to further progress called for a deeper understanding of the pathophysiology behind respiratory insufficiency of the premature infant. [link.springer.com]

Bardet-Biedl syndrome: Genetics, molecular pathophysiology, and disease management. Indian J Ophthalmol. 2016;64(9): 620-627. Hufnagel RB, Arno G, Hein ND, et al. [rarediseases.org]

Report of three cases with further delineation of the clinical, pathophysiological, and genetic aspects of the disorder. Medicine (Baltimore) 52: 53–71. [preventiongenetics.com]

Finding in this case suggests that hyperinsulinemia is a secondary event in Alström syndrome, and early-commenced treatment prevents hyperinsulinemia. [ncbi.nlm.nih.gov]

[…] them from getting worse Alström Syndrome is an inherited disorder, and hence, no preventive measures have been reported. [dovemed.com]

Prevention - Alström syndrome Prevention for Alström Syndrome is considered to be harder compared to other diseases/syndromes because it is an inherited condition. [checkorphan.org]

CONCLUSIONS Regular follow-ups are needed to recognize and possibly prevent late-appearing complications. Received February 14, 1994. Accepted January 5, 1995. [care.diabetesjournals.org]

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.