About sandhoff disease

What is sandhoff disease?

Sandhoff disease is a lipid storage disorder characterized by a progressive deterioration of the central nervous system. The clinical symptoms of Sandhoff disease are identical to Tay-Sachs disease. Sandhoff disease is an autosomal recessive genetic disorder caused by an abnormal gene for the beta subunit of the hexosaminidase B enzyme. This gene abnormality results in a deficiency of hexosaminidase A and B that results in accumulation of fats (lipids) called GM2 gangliosides in the neurons and other tissues.

What are the symptoms for sandhoff disease?

The most common type of Sandhoff disease causes rapidly progressing mental and motor decline in infancy. Within the first six months of life, infants with Sandhoff disease will experience weakness. They lose skills like turning over, sitting, and crawling. They can also have trouble with feeding, overreaction to loud sudden noises, delayed speech, early blindness, seizures, heart murmur, and continuously tight muscles (spasticity). A doctor may notice Red spots in the back of the eye (cherry-Red spots of the macula) and an abnormal reflex of the foot that indicates damage to the nervous system (the Babinski reflex). Other signs of Sandhoff disease can include a Large head (macrocephaly) and unique facial features. Infants with this form of Sandhoff disease usually do not live past 2-5 years.

Juvenile and Adult Sandhoff Disease Sandhoff disease can also happen in older children and adults. These individuals will experience a slower mental and motor decline than in infantile Sandhoff disease. The onset and severity of symptoms can vary. A specific symptom of later-onset Sandhoff disease is Muscle Weakness affecting the muscles of the arms, legs, and hips. Other symptoms include muscle loss (muscle atrophy), Balance problems, uncontrollable muscle contraction (dystonia), damage to nerves controlling involuntary bodily functions (autonomic neuropathy), a loss of intellectual function (cognitive dysfunction), psychiatric illness and dementia.

What are the causes for sandhoff disease?

Sandhoff disease is caused by harmful mutations in a gene called HEXB. These gene mutations cause decreased amounts of two important enzymes: beta-hexosaminidase A and beta-hexosaminidase B. These enzymes are found in the recycling centers (lysosomes) of the cell and their job is to break down fatty substances called GM2 gangliosides and globosides. The symptoms of Sandhoff disease happen because these fats (lipids) accumulate in harmful amounts in the brain and nerve cells. This damages the brain and spinal cord (central nervous system).

Sandhoff disease is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

What are the treatments for sandhoff disease?

There is currently no cure for Sandhoff disease. Management is based on the symptoms and is mostly supportive. Supportive treatment includes ensuring proper nutrition and hydration, keeping the airway open, and seizure control with anticonvulsants.

Genetic counseling is recommended for affected individuals and their families.

What are the risk factors for sandhoff disease?

Sandhoff disease is a rare disorder that is estimated to affect 1 in 1,000,000 individuals. It affects males and females in equal numbers. Sandhoff disease occurs in multiple populations but may be most common in the Creole population of Argentina, Metis citizens of Saskatchewan, Canada and people with Lebanese ancestry.

Is there a cure/medications for sandhoff disease?

Sandhoff disease is an exceedingly rare lysosomal storage condition. It induces nerve cell damage (neurodegeneration). This causes issues with thinking and movement. Sandhoff illness is caused by faulty HEXB gene mutations. Negative alterations in this gene result in lower levels of two enzymes in the cell's recycling centers (lysosomes). Certain fats (lipids) accumulate in enormous levels in nerve cells in the absence of these enzymes. This causes brain and spinal cord damage (central nervous system).

1. Sandhoff syndrome currently lacks a standard therapy as well as a cure. A patient suffering from the disease, on the other hand, needs a sufficient diet, hydration, and the maintenance of clear airways.
2. To alleviate some of the symptoms associated with Sandhoff illness, the patient might take anticonvulsants to control seizures or drugs to treat respiratory infections, as well as follow a strict diet consisting of pureed foods due to swallowing difficulties.
3. Infants with the condition typically die by the age of three as a result of respiratory infections. The patient must be constantly monitored because they may aspirate or lack the ability to switch from the passageway to their lungs to their stomach, and their spit travels to the lungs, producing bronchopneumonia.
4. Since the patient is unable to cough, they must undergo a treatment that shakes their body in order to eliminate the mucus from the walls of their lungs. Patients are also given medication to alleviate symptoms such as seizures.
5. The government is currently evaluating many treatments in mice, including N-butyl-deoxynojirimycin, as well as stem cell therapy in humans and other medical interventions that are recruiting test subjects.
6. A Sandhoff disease study that demonstrated proof of concept for gene therapy in a human model system using CRISPR and viral gene repair opens the door to clinical trials for disease cure. The ultra-rare incidence is a significant barrier to overcome in clinical trials.

Bone development that is abnormal,Uncomfortable movements,The eyeballs have "cherry-red" spots,Enlarged head (macrocephaly) or enlarged internal organs, particularly the liver and spleen (organomegaly),Reactions to loud noises that are exaggerated (startle response),Infections of the respiratory system (breathing),Motor skills as as crawling, sitting up, and rolling over develop slowly,Muscular weakness, difficulty regulating muscles (ataxia), or muscle twitching (myoclonus)
Hearing impairment,Intellectual disabilities,Loss of vision,Death occurs early,Paralysis,Seizures

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