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]

• Turkish

  The three affected sisters, from a consanguineous Turkish family, with the characteristic features of Alström syndrome, were clinically diagnosed in 1987 and followed for 20 years. [ncbi.nlm.nih.gov]

  Interestingly, the apolipoprotein E R158C mutation, which is particularly rare in the Turkish population compared to central Europeans, 19 was found in two of the three sibs. [jmg.bmj.com]

• 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]

  Heart failure is mainly treated with angiotensinogen-converting enzyme (ACE) inhibitors, diuretics, and digoxin. [orpha.net]

  Minor criteria: Obesity and/or insulin resistance and/or Type 2 Diabetes History of dilated cardiomyopathy with congestive heart failure. [en.wikipedia.org]

• 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]

• 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]

  Minor Criteria Obesity and/or insulin resistance and/or Type 2 Diabetes History of dilated cardiomyopathy with congestive heart failure Hearing loss Hepatic dysfunction Renal failure Advanced bone age 15 years – adulthood 2 major and 2 minor criteria [medcaretips.com]

  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]

• 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]

  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]

  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]

  […] 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

  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]

  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]

  Kidney failure may also occur. During childhood, patients suffer deteriorating eyesight which may include nystagmus and photophobia which often leads to blindness. Hearing loss and Type 2 diabetes is also common. [ciliopathyalliance.org]

• Anorchia

  Unilateral anorchia with hypergonadotropic hypogonadism is another unique feature of our case. [ncbi.nlm.nih.gov]

• Secondary Amenorrhea

  We evaluated a 15-year-old girl for secondary amenorrhea and excessive hair growth on the face. On examination, she was found to have alopecia, hirsutism, acanthosis, and large sweaty hands. [ijem.in]

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].

• Albuminuria

  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 [symptoma.com]

• Lymphocytic Infiltrate

  Liver biopsy showed fatty liver, lymphocytic infiltration, and piecemeal necrosis. The second sib had had elevated gamma-glutamyltransferase levels since she was 10 years old. [ncbi.nlm.nih.gov]

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]

Treatment Currently, therapy for patients with Alstrom syndrome is limited in scope. Studies are underway to develop treatment strategies which can limit or restrict the progression of disease manifestations. [news-medical.net]

Standard heart failure treatments are successful for long periods. [diapedia.org]

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

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]

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]

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]

[…] heterozygous and homozygous mapping approaches have all been useful in this regard, and research is proceeding into the use of combinations of different tools in consanguineous families and non-classical phenotypes to find new genes which are involved in the etiology [news-medical.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]

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

The Alström syndrome: report of three cases with further delineation of the clinical, pathophysiological, and genetic aspects of the disorder. Medicine. 1973;52:53-71. 7. Tremblay F, La Roche RG, Shea SE, Ludman MD. [healio.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]

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]

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

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