The GM1

GM1

GM1 the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain...

 gangliosidoses are caused by a deficiency of beta-galactosidase

Beta-galactosidase

β-galactosidase, also called beta-gal or β-gal, is a hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides. Substrates of different β-galactosidases include ganglioside GM1, lactosylceramides, lactose, and various glycoproteins...

, with resulting abnormal storage of acidic lipid

Lipid

Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

 materials in cells

Cell (biology)

The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 of the central and peripheral nervous system

Nervous system

The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...

s, but particularly in the nerve cells.

Early infantile GM1

Symptoms of early infantile GM1 (the most severe subtype, with onset shortly after birth) may include neurodegeneration

Neurodegeneration

Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many...

, seizures, liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 (hepatomegaly

Hepatomegaly

Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...

) and spleen

Spleen

The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

 (splenomegaly

Splenomegaly

Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...

) enlargement, coarsening of facial features, skeletal irregularities, joint stiffness, distended abdomen, muscle weakness, exaggerated startle response to sound, and problems with gait

Gait

Gait is the pattern of movement of the limbs of animals, including humans, during locomotion over a solid substrate. Most animals use a variety of gaits, selecting gait based on speed, terrain, the need to maneuver, and energetic efficiency...

.

About half of affected patients develop cherry-red spots in the eye

Human eye

The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...

.

Children may be deaf and blind

Blindness

Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...

 by age 1 and often die by age 3 from cardiac complications or pneumonia

Pneumonia

Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

.

Autosomal recessive disorder; beta-galactosidase deficiency; neuronal storage of GM1 ganglioside and visceral storage of galactosyl oligosaccharides and keratan sulfate.
Early psychomotor deterioration: decreased activity and lethargy in the �first weeks; never sit; feeding problems - failure to thrive; visual failure (nystagmus �noted) by 6 months; initial hypotonia; later spasticity with pyramidal signs; secondary �microcephaly develops; decerebrate rigidity by 1 year and death by age 1-2 years �(due to pneumonia and respiratory failure); some have hyperacusis.
Macular cherry-red spots in 50% by 6-10 months; corneal opacities in some
Facial dysmorphology: frontal bossing, wide nasal bridge, facial edema (puffy �eyelids); peripheral edema, epicanthus, long upper lip, microretrognathia, gingival hypertrophy (thick alveolar ridges), macroglossia
Hepatomegaly by 6 months and splenomegaly later; some have cardiac failure
Skeletal deformities: flexion contractures noted by 3 months; early subperiosteal �bone formation (may be present at birth); diaphyseal widening later; demineralization; thoracolumbar vertebral hypoplasia and beaking at age 3-6 months; kyphoscoliosis. Dysostosis multiplex (as in the mucopolysaccharidoses).
10-80% of peripheral lymphocytes are vacuolated; foamy histiocytes in bone marrow; visceral mucopolysaccharide storage similar to that in Hurler disease; GM1 storage �in cerebral gray matter is 10 fold elevated (20-50-fold increased in viscera)
Galactose-containing oligosacchariduria and moderate keratan sulfaturia
Morquio disease Type B: Mutations with higher residual beta-galactosidase activity�for the GM1 substrate than for keratan sulfate and other galactose-containing oligosaccharides have minimal neurologic involvement but severe dysostosis �resembling Morquio disease type A (Mucopolysaccharidosis type 4).

Adapted from Lyon GL et al, Neurology of Hereditary Metabolic Diseases of Children, ed 2, 1996, p53-55

Late infantile GM1

Onset of late infantile GM1 is typically between ages 1 and 3 years.

Neurological symptoms include ataxia

Ataxia

Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...

, seizures, dementia

Dementia

Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

, and difficulties with speech.

Adult GM1

Onset of adult GM1 is between ages 3 and 30.

Symptoms include muscle atrophy, neurological complications that are less severe and progress at a slower rate than in other forms of the disorder, corneal clouding in some patients, and dystonia

Dystonia

Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...

 (sustained muscle contractions that cause twisting and repetitive movements or abnormal postures). Angiokeratomas may develop on the lower part of the trunk of the body. Most patients have a normal size liver and spleen.