Sandhoff disease is a disorder caused by a lack of two important enzymes, hexosaminidase A and hexosaminidase B, which are usually found in cell structures called lysosomes.
Lysosomes normally break down substances and act like recycling centers in the cells. Without these enzymes, a fatty substance called GM2 ganglioside and other molecules build up to harmful levels, leading to the gradual destruction of nerve cells. The symptoms can vary depending on the form of the disease.
Infantile (Classic) Form: The most common and severe type of Sandhoff disease appears in babies. Infants with this form seem normal until around 3 to 6 months old when their development slows, and the muscles they use for movement become weak. They lose motor skills like turning over, sitting, and crawling. They also react strongly to loud noises. As the disease continues, affected children have seizures, vision and hearing loss, intellectual disability, and paralysis. A key sign of this disorder is a cherry-red spot in the eyes. Some affected children may also have enlarged organs or bone issues.
Juvenile-Onset Form: A less severe, rarer form of Sandhoff disease occurs when a person has mutations causing a partial enzyme deficiency. Signs and symptoms can vary widely and may start in childhood or adolescence. Individuals may experience muscle weakness, difficulty coordinating movement, speech problems, recurrent respiratory infections, and seizures.
Late-Onset Form: The late-onset form can be challenging to diagnose. Early signs may include clumsiness and muscle weakness in the legs. Over time, individuals with late-onset Sandhoff disease may need help with mobility and may face speech and swallowing difficulties. Around 40% of affected adults may experience mental health issues like bipolar disorder or psychotic episodes.
There’s currently no specific treatment or cure for Sandhoff disease. Treatment focuses on supportive care for symptoms, including medications to control seizures and providing nutritional and respiratory support.
Sandhoff disease is caused by pathogenic (disease-causing) variants in the HEXB gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
Other names for this condition are beta-hexosaminidase-beta-subunit deficiency, GM2 gangliosidosis, type 2, hexosaminidase A and B deficiency disease, and Sandhoff-Jatzkewitz-Pilz disease.