What is Sandhoff disease?
Sandhoff disease is a rare, inherited metabolic condition that affects how the brain, nervous system and other organs work. It happens because the body can’t properly break down and clear certain fatty substances. Over time this fat builds up inside nerve cells, making it harder for them to work as they should.
The condition is usually noticed in the first year of life, with symptoms appearing between 3-6 months. More rarely it can appear later in childhood or early adulthood, often with milder symptoms.
Sandhoff disease is closely related to Tay-Sachs disease, but it can affect other organs as well as the brain. It is a lifelong condition, but medicines and ongoing care can help to manage symptoms and improve quality of life.
What causes Sandhoff disease?
Sandhoff disease is caused by a change in a gene that provides instructions for making important enzymes that help the body break down fat. These enzymes are called hexosaminidase A (Hex-A) and hexosaminidase B (Hex-B) and both must be affected for the condition to develop.
When these enzymes don’t work properly, the body can’t clear away a fatty substance known as GM2 ganglioside. Instead, it collects inside cells, particularly in the brain and nervous system. It can also affect the liver and spleen. Over time, this build up stops cells working as they should.
Sandhoff disease is inherited in an autosomal recessive pattern. This means that two altered copies of the gene must be inherited to develop the condition. Parents and other family members may be carriers of the gene change without having any symptoms themselves.
What are the symptoms of Sandhoff disease?
The symptoms of Sandhoff disease vary depending on the age at which they appear and may include:
Infantile Sandhoff disease
- Increased startle response – being unusually sensitive to loud noises or sudden movements
- Losing skills that had already been learned – such as sitting, rolling, or responding to familiar voices
- Changes in movement and muscle control – including weakness, stiffness, or reduced movement
- Feeding or swallowing difficulties – which may affect eating and growth
- Hearing and vision changes
- Seizures – shaking, stiffness, or changes in awareness
- Enlarged liver or spleen – which may cause a swollen tummy
- Cherry-red spot in the eyes – a common change in the eyes that helps doctors diagnose the condition
Later-onset Sandhoff disease
- Problems with balance and coordination – falls may be more likely
- Muscle weakness or cramps – pain or stiffness, making movement harder
- Slurred or slower speech – speech may be more difficult to understand
- Changes in memory or concentration – difficulty remembering things, or carrying out tasks
- Low mood – including sadness and lack of motivation
- Difficulty swallowing – which may affect eating and drinking
Symptoms of later-onset Sandhoff disease usually develop gradually and can vary widely from person to person.
