Alström syndrome (AS), also called Alström–Hallgren syndrome, is a very rare

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

genetic disorder characterised by childhood obesity and multiple organ dysfunction. Symptoms include early-onset

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...

cone-rod dystrophy A cone dystrophy is an inherited ocular disorder characterized by the loss of cone cells, the photoreceptors responsible for both central and color vision. Presentation The most common symptoms of cone dystrophy are vision loss (age of onset r ...

resulting in blindness,

sensorineural hearing loss Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve (cranial nerve VIII). SNHL accounts for about 90% of rep ...

and

dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Co ...

Endocrine disorders Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology. Types of disease Broadly speaking, endocrine disorders may be subdivided into three groups: # Endocrin ...

typically also occur, such as hypergonadotrophic hypogonadism and

hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...

, as well as

acanthosis nigricans Acanthosis nigricans is a medical sign characterised by brown-to-black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds, such as the posterior and lateral folds of the neck, the armpits, groin, navel, fore ...

resulting from

hyperinsulinemia Hyperinsulinemia is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabol ...

. Developmental delay is seen in almost half of people with Alström syndrome. It is caused by mutations in the gene '' ALMS1'', which is involved in the formation of cellular

cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...

, making Alström syndrome a

ciliopathy A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function while ...

. At least 239 disease-causing mutations in ''ALMS1'' have been described . Alström syndrome is sometimes confused with

Bardet–Biedl syndrome Bardet–Biedl syndrome (BBS) is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized by rod/cone dystrophy, polydactyly, central obesity, hypogonadism, and kidney dysfunction in so ...

, another ciliopathy which has similar symptoms, but Bardet–Biedl syndrome tends to have later onset in its symptoms, includes

polydactyly Polydactyly or polydactylism (), also known as hyperdactyly, is an anomaly in humans and animals resulting in supernumerary fingers and/or toes. Polydactyly is the opposite of oligodactyly (fewer fingers or toes). Signs and symptoms In humans ...

and is caused by mutations in ''BBS'' genes. There is no cure for Alström syndrome. Treatments target the individual symptoms and can include diet,

corrective lenses A corrective lens is a lens (i.e. a transmissive optical device) that is typically worn in front of the eye to improve daily vision. The most common use is to treat refractive errors: myopia, hypermetropia, astigmatism, and presbyopia. Glas ...

hearing aids A hearing aid is a device designed to improve hearing by making sound audible to a person with hearing loss. Hearing aids are classified as medical devices in most countries, and regulated by the respective regulations. Small audio amplifiers su ...

, medications for diabetes and heart issues and dialysis and transplantation in the case of

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

or liver failure. Prognosis varies depending on the specific combination of symptoms, but individuals with Alström syndrome rarely live beyond 50. At least 900 cases have been reported. Prevalence is fewer than 1 in 1,000,000 individuals in the general population, but the disorder is much more common in

Acadians The Acadians (french: Acadiens , ) are an ethnic group descended from the French who settled in the New France colony of Acadia during the 17th and 18th centuries. Most Acadians live in the region of Acadia, as it is the region where the des ...

, both in

Nova Scotia Nova Scotia ( ; ; ) is one of the thirteen provinces and territories of Canada. It is one of the three Maritime provinces and one of the four Atlantic provinces. Nova Scotia is Latin for "New Scotland". Most of the population are native Eng ...

and

Louisiana Louisiana , group=pronunciation (French: ''La Louisiane'') is a state in the Deep South and South Central regions of the United States. It is the 20th-smallest by area and the 25th most populous of the 50 U.S. states. Louisiana is borde ...

. It was first described by Swedish psychiatrist

Carl-Henry Alström Carl-Henry Alström (3 May 1907 – 1993) was a Swedish psychiatrist who described a syndrome now named for him, Alström syndrome, a hereditary disorder that characteristically includes obesity in childhood, nerve deafness, and retinal degenerati ...

and his three associates, B. Hallgren, I. B. Nilsson and H. Asander, in 1959.

Signs and symptoms

Symptoms for Alström syndrome generally appear during infancy with great variability in age. Some of the symptoms include: * Heart failure (

) in over 60% of cases, usually within the first few weeks after birth, but sometimes the onset is in adolescence or adulthood. *

Light sensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicity ...

and vision problems (

) in all cases, usually within 15 months of birth and progressively worsening until about 20 years of age * Delays in early, developmental milestones in 50% of cases,

learning disabilities Learning disability, learning disorder, or learning difficulty (British English) is a condition in the brain that causes difficulties comprehending or processing information and can be caused by several different factors. Given the "difficult ...

in about 30% of cases *

Obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

in 100% of cases, apparent by 5 years of age but often apparent in infancy (Alström infants usually have normal birth weights, and by adolescence, weights tend to be in the high-normal to normal range.) *

Nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

(usually affects the children), one of the first symptoms to occur which causes involuntary rapid eye movement. * Mild to moderate bilateral

. * Type 2

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

usually occurs in early childhood. *

Hyperinsulinemia Hyperinsulinemia is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabol ...

insulin resistance Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...

—development of high level of insulin in blood. *

Hypertriglyceridemia Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and h ...

Steatosis Steatosis, also called fatty change, is abnormal retention of fat (lipids) within a cell or organ. Steatosis most often affects the liver – the primary organ of lipid metabolism – where the condition is commonly referred to as fatty liver disea ...

(fatty liver) and elevated

transaminase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid co ...

s (liver enzymes) often develop in childhood and can progress in some patients to cirrhosis and liver failure. * Endocrine dysfunctions may occur where the patient may experience an under or over active thyroid gland, weak growth hormone, increased androgen in females and low testosterone in males. * Slowly progressive kidney failure can occur in the second to fourth decade of life.

Cause

Alström syndrome is caused by a mutation in the '' ALMS1'' gene, located on the short arm of

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost e ...

(2p13.2). The gene mutation is inherited as an autosomal recessive trait. This means both parents have to pass a defective copy of the ''ALMS1'' gene in order for their child to have the syndrome, even though the parents may not show signs or symptoms of the condition. The ''ALMS1'' gene contains instructions to encode a specific protein known as ALMS1. The protein then is involved in ciliary function,

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

control and

intracellular transport Intracellular transport is the movement of vesicles and substances within a cell. Intracellular transport is required for maintaining homeostasis within the cell by responding to physiological signals. Proteins synthesized in the cytosol are dis ...

. In addition, the protein is expressed in all organ tissues of the body. It has a role in the proper function, maintenance and formation of cilia, which are found in all types of cells in the body. At least 239 disease-causing mutations in ''ALMS1'' have been described . Most of these mutations have led to the production of a dysfunctional version of the ALSM1 protein which are present in tissues, but at low levels.

Diagnosis

It is possible to clinically detect Alström syndrome in infancy, but more frequently, it is detected much later, as doctors tend to detect symptoms as separate problems. Currently, Alström syndrome is often diagnosed clinically, since

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

is costly and only available on a limited basis. A physical examination would be needed to properly diagnose the patient. Certain physical characteristics can determine if the patient has some type of genetic disorder. Usually, a geneticist would perform the physical examination by measuring the distance around the head, distance between the eyes and the length of arms and legs. In addition, examinations for the nervous system or the eyes may be performed. Various imaging studies like computerized tomography scans (CT),

Magnetic Resonance Imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...

(MRI) or

X-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...

s are used to see the structures within the body. Family and personal medical history are required. Information about the health of an individual is crucial because it provides traces to a genetic diagnosis. Laboratory tests, particularly genetic testing, are performed to diagnose genetic disorders. Some of the types of genetic testing are molecular, biochemical and chromosomal. Other laboratory tests performed may measure levels of certain substances in urine and blood that can also help suggest a diagnosis.

Related disorders

Recent findings in genetic research have suggested that a large number of

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

s, both

genetic syndromes A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...

and

genetic diseases A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying,

phenotypically In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

-observed disorders. Thus, Alstrom syndrome is a

. Other known ciliopathies include

primary ciliary dyskinesia Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, Fallopian tube, and flagella of ...

polycystic kidney Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a genetic disorder in which the renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney. These cy ...

and

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the sig ...

nephronophthisis Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease. The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause o ...

Meckel–Gruber syndrome Meckel-Gruber syndrome is a rare, lethal ciliopathic genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations (occipital encephalocele), polydactyly (postaxial), hepatic developmental defects, and pulmonary ...

and some forms of retinal degeneration.

Diagnostic criteria

Marshall JD et al. provided a comprehensive guidance for diagnostic criteria in their 2007 publication. Birth – 2 years: Minimum diagnosis requires 2 major criteria or 1 major and 2 minor criteria. Major criteria are: # ''ALMS1'' mutation in 1 allele and/or family history of Alström syndrome # Vision pathology (nystagmus, photophobia). Minor criteria are: # Obesity # Dilated cardiomyopathy with congestive heart failure. Other variable supportive evidence: Recurrent pulmonary infections, normal digits, delayed developmental milestones. At 3–14 years of age: 2 major criteria or 1 major and 3 minor criteria. Major criteria are: # ''ALMS1'' mutation in 1 allele and/or family history of Alström syndrome, # Vision pathology (

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...

, diminished acuity). If old enough for testing: cone dystrophy by ERG. Minor criteria: #

and/or

Type 2 Diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...

# History of dilated

cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...

with

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

Hearing loss Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...

Liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

dysfunction #

Kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

# Advanced bone age Variable supportive evidence: Recurrent pulmonary infections, normal digits, delayed developmental milestones, hyperlipidemia, scoliosis, flat wide feet hypothyroidism, hypertension, recurrent urinary tract infection, growth hormone deficiency. Presentation 15 years – adulthood: 2 major and 2 minor criteria or 1 major and 4 minor criteria. Major criteria are: # ''ALMS1'' mutation in 1 allele and/or family history of Alström syndrome. # Vision pathology (history of nystagmus in infancy/childhood, legal blindness, cone and rod dystrophy by ERG). 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 # Short stature # Males: hypogonadism, Females: irregular menses and/or hyperandrogenism Other supportive features: Recurrent pulmonary infections, normal digits, history of developmental delay, hyperlipidemia, scoliosis, flat wide feet, hypothyroidism, hypertension, recurrent urinary tract infections/urinary dysfunction, growth hormone deficiency, alopecia.

Prevention

Prevention for Alström syndrome is considered to be harder compared to other diseases/syndromes because it is an inherited condition. However, there are other options that are available for parents with a family history of Alström syndrome. Genetic testing and counseling are available where individuals are able to meet with a genetic counselor to discuss risks of having the children with the disease. The genetic counselor may also help determine whether individuals carry the defective ALSM1 gene before the individuals conceive a child. Some of the tests the genetic counselors perform include

chorionic villus sampling Chorionic villus sampling (CVS), sometimes called "chorionic ''villous'' sampling" (as "villous" is the adjectival form of the word "villus"), is a form of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus. It ent ...

(CVS),

preimplantation genetic diagnosis Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...

(PGD) and

amniocentesis Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ne ...

. With PGD, the embryos are tested for the ALSM1 gene and only the embryos that are not affected may be chosen for implantation via in vitro fertilization.

Treatment

There is no cure for Alström syndrome; however, there are treatment aims to reduce the symptoms and prevent further complications. Some of these treatment aims include: * Corrective lenses: tinted lenses that help with the sensitivity from bright lights. The patients may have to adapt to reading in Braille, use adaptive equipment, mobility aids and adaptive computing skills. * Education: patients with Alström syndrome who have intellectual disabilities must have access to education. They must be able to receive free and appropriate education. Some Alström syndrome patients are educated in normal classrooms. Other patients have to take special education classes or attend to specialized schools that are prepared to teach children with disabilities. Staff members from schools have to consult with patient's parents or caregivers in order to design an education plan based on the child's needs. In addition, the school may document the progress of the child in order to confirm that the child's needs are being met. * Hearing aids: the battery-operated devices are available in three styles: behind the ear, in the ear and inside the ear canal. Behind the ear aims for mild-to-profound hearing loss. In the ear aims for mild to severe hearing loss. Lastly, the canal device is aimed for mild to moderately severe hearing loss. Patients that have severe hearing loss may benefit from a cochlear implant. * Diet: an appropriate and healthy diet is necessary for individuals with Alström syndrome because it could potentially decreases chances of obesity or diabetes. * Occupational therapy: the therapist helps the child learn skills to help him or her perform basic daily tasks like eating, getting dressed and communicating with others. * Physical Activity: exercising reduces chances of being obese and helping control blood sugar levels. * Dialysis: helps restore filtering function. With hemodialysis, a patient's blood circulates into an external filter and clean. The filtered blood is then returned into the body. With

peritoneal dialysis Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte pro ...

, fluid containing dextrose is introduced into the abdomen by a tube. The solution then absorbs the wastes into the body and is then removed. * Transplantation: patients that endure a kidney failure may undergo a kidney transplantation. * Surgery: if the patient endures severe scoliosis or

kyphosis Kyphosis is an abnormally excessive convex curvature of the spine as it occurs in the thoracic and sacral regions. Abnormal inward concave ''lordotic'' curving of the cervical and lumbar regions of the spine is called lordosis. It can result fr ...

, surgery may be required.

Medication

* Antibiotics: patients with lung problems will be prescribed antibiotics because they are more prone to infections like bronchitis. * Oral diabetes medications: are taken by mouth to treat diabetes. Can be taken combined into a single pill, which may be more effective and convenient for people with diabetes. It is usually taken once or twice daily before meals. Some of these medications includes: **

Meglitinide Meglitinides or glinides are a class of drugs used to treat type 2 diabetes. Drugs Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997. Other drugs in this class include nateglinide (Starlix) and mitiglin ...

s (repaglinide and nateglinide): taken to stimulate the cells found in the pancreas to release insulin. These drugs are taken by mouth daily before each meal and could cause a drop in blood sugar. **

Metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...

(biguanide): decreases the amount blood sugar being released by the liver and by stimulating the cells within muscles to take up blood sugar. Taken twice daily. **

Thiazolidinedione The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used i ...

s (rosiglitazone and pioglitazone): taken to help insulin work more efficiently in muscle and fat cells causing the liver to release less glucose. Is associated with heart failure. ** Dipeptidyl peptidase IV (DPP-4) inhibitors (sitagliptin): helps with improving blood sugar levels by decreasing the action of an enzyme breaking down

GLP-1 Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certa ...

(lowers the blood sugar level). ** Injected diabetes medicine: taken by an injection into the fat below the skin. Sometimes referred as subcutaneous injections. Some of these medications include the following: **

Pramlintide Pramlintide (trade name Symlin) is an injectable amylin analogue drug for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals (now a wholly owned subsidiary of AstraZeneca). Pramlintide is sold as an acetate salt. Pharmacology Pram ...

(Symlin): is an Amylin agonist. It acts centrally (via the brain) to reduce food intake and blood sugar. It is most commonly used at mealtimes by people with type 1 and type 2 diabetes. **

Exenatide Exenatide, sold under the brand name Byetta and Bydureon among others, is a medication used to treat diabetes mellitus type 2. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after ...

(Byetta): synthetic form of exendin-4 ( a GLP-1 receptor agonist that increases secretion of insulin, decreases the secretion of glucagon from the pancreas and reduces food intake). * Cholesterol-lowering medications: is necessary when cholesterol levels are high.

HMG-CoA β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase. The research of ...

reductase inhibitors, also called "statins," effectively lower levels of low-density lipoprotein, cholesterol and triglycerides. High-dose nicotinic acid (niacin) may also reduce cholesterol levels. * Heart medications:

Angiotensin-converting enzyme Angiotensin-converting enzyme (), or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasoconstr ...

(ACE) inhibitors, diuretics,

digoxin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is on ...

and beta-blockers may help with the management of cardiomyopathy and heart failure.

Prognosis

A prognosis for Alström syndrome is complicated because it widely varies. Any person that has the syndrome have different set of disorders. Permanent blindness, deafness and type 2 diabetes may occur. Liver and kidney failure can progressively get worse. The life expectancy is usually reduced and the patients rarely live past 50 years old.

Research

The Jackson Laboratory in

Bar Harbor Bar Harbor is a resort town on Mount Desert Island in Hancock County, Maine, United States. As of the 2020 census, its population is 5,089. During the summer and fall seasons, it is a popular tourist destination and, until a catastrophic fire ...

Maine Maine () is a state in the New England and Northeastern regions of the United States. It borders New Hampshire to the west, the Gulf of Maine to the southeast, and the Canadian provinces of New Brunswick and Quebec to the northeast and north ...

, USA with the

University of Southampton , mottoeng = The Heights Yield to Endeavour , type = Public research university , established = 1862 – Hartley Institution1902 – Hartley University College1913 – Southampton University Coll ...

, UK isolated the single

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

('' ALMS1'') responsible for Alström syndrome. Research was conducted in 2014 on Alström syndrome patients regarding degeneration and plasticity of the optic pathway. The functional and structural changes have been investigated on the optic pathway in Alström syndrome by using magnetic resonance imaging to provide better insight on the underlying pathogenic mechanisms. Eleven patients with the syndrome (mean age of 23 years, 5 females, 6 males) underwent a brain MRI. The protocol also included conventional sequences, resting-state functional MRI and diffusion tensor imaging. Results found that patients with Alström syndrome had occipital regions with decreased white matter volume as well as decreased gray matter volume sparing the occipital poles. The diffused fractional

anisotropy Anisotropy () is the property of a material which allows it to change or assume different properties in different directions, as opposed to isotropy. It can be defined as a difference, when measured along different axes, in a material's physic ...

decreased and the radial

diffusivity Diffusivity is a rate of diffusion, a measure of the rate at which particles or heat or fluids can spread. It is measured differently for different mediums. Diffusivity may refer to: *Thermal diffusivity, diffusivity of heat *Diffusivity of mass: ...

increased while mean and axial diffusivities were normal. Lastly, the reduced connectivity in the medial visual network was strikingly sparing the occipital poles. The conclusion of the research was that the protean occipital brain changes in patients with Alström syndrome. They are likely to reflect coexistence of diffuse primary

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...

derangement, anterograde trans-synaptic degeneration and complex cortical reorganization that affect the posterior and anterior visual cortex.

References

External links

{{DEFAULTSORT:Alstrom Syndrome Ciliopathy Syndromes with obesity Syndromes with sensorineural hearing loss Syndromes affecting the retina Syndromes including diabetes mellitus Rare genetic syndromes