Symptoms of the following disorders can be similar to those of Tay-Sachs disease. Comparisons may be useful for a differential diagnosis:

Sandhoff disease is a rare inherited lipid storage disorder resulting in the progressive deterioration of the central nervous system (neurodegenerative disorder). A deficiency of the enzymes hexosaminidase A and B results in the accumulation of certain fats (lipids) in the brain and other organs of the body. Symptoms in infants may include feeding problems, general weakness, and an exaggerated startle reflex in response to sudden loud noise. Motor delays and mental impairment are progressive. Sandhoff disease is a severe form of Tay-Sachs disease and is not limited to any particular ethnic group. Sandhoff disease is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Sandhoff” as your search term in the Rare Disease Database.)

Leigh’s disease is a rare inherited neurometabolic disorder. It is characterized by the degeneration of the central nervous system (i.e., brain, spinal cord, and optic nerve). The symptoms of Leigh’s disease usually begin between the ages of three months and two years. Symptoms are associated with progressive neurological deterioration and may include loss of previously acquired motor skills, loss of appetite, vomiting, irritability, and/or seizure activity. As Leigh’s disease progresses, symptoms may also include generalized weakness, lack of muscle tone, and episodes of lactic acidosis, which may lead to impairment of respiratory and kidney function. In most cases, Leigh’s disease is inherited as an autosomal recessive genetic trait. However, autosomal dominant, X-linked recessive, and mitochondrial inheritance have also been noted. There appear to be several different types of genetically determined enzyme defects that can cause Leigh’s disease. (For more information on this disorder, choose “Leigh’s” as your search term in the Rare Disease Database.)

The neuronal ceroid lipofuscinoses (NCL) are a group of progressive degenerative neurometabolic diseases. These diseases share certain similar symptoms and are distinguished in part by the age at which such symptoms appear. Two forms occur during infancy: Santavuori disease (infantile type) and Jansky-Bielschowsky disease (late infantile type). These disorders are characterized by a delay in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor retardation). In addition, affected infants begin to lose previously acquired physical and mental abilities (developmental regression). Affected infants may then experience a variety of symptoms including episodes of uncontrolled electrical disturbances in the brain (seizures), impaired ability to coordinate voluntary movements (cerebellar ataxia), abnormally diminished muscle tone (hypotonia), and repeated, brief, shock-like muscle spasms of the arms, legs, or entire body (myoclonic seizures). Affected infants also experience progressive visual impairment due to deterioration of the nerves of the eyes (optic nerves) that transmit impulses from the retina to the brain (optic atrophy). Neurological impairment progresses and may result in an inability to move voluntarily (immobility), sudden involuntary muscle spasms (spasticity), and lack of response to stimuli in the environment. Life-threatening complications may develop by the end of the first decade. (For more information, choose the specific disorder name as your search term in the Rare Disease Database.)

Symptoms of the following disorders can be similar to those of late-onset Tay-Sachs disease. Comparisons may be useful for a differential diagnosis:

Kugelberg-Welander syndrome, also known as spinal muscular atrophy type III, is a rare inherited disorder. Major symptoms may include wasting and weakness in the muscles of the arms and legs, twitching, clumsiness in walking, and eventual loss of reflexes. Kugelberg-Welander syndrome is not apparent at birth; it usually appears during the first 10 to 20 years of life. (For more information on this disorder, choose “Kugelberg-Welander” as your search term in the Rare Disease Database.)

Amyotrophic lateral sclerosis (ALS) is characterized by slight muscle weakness, clumsy hand movements, and/or difficulty performing tasks that require delicate movements of the fingers and/or hands. Muscular weakness in the legs may cause tripping and falling. People with ALS may have difficulty swallowing (dysphagia), and speech may be slowed. Additional symptoms of this disorder include progressive weakness of the lips and impairment and/or loss of function of the tongue, mouth, and/or voice box (bulbar symptoms). Leg cramps may occur during the night, most frequently in the calf and/or thigh muscles. ALS may progress quickly or slowly, and gradually additional muscles become involved. Individuals with ALS may also exhibit uncontrolled twitching of muscles (fasciculations), stiffness in the legs, and/or coughing. As the ability to move becomes progressively impaired, people with this disease are at increased risk for respiratory failure. The exact cause of ALS is unknown. (For more information on this disorder, choose “Amyotrophic Lateral Sclerosis” as your search term in the Rare Disease Database.)