Exhaustive list of GM1 Symptoms

 I tried to make this list as comprehensive with regards to possible symptoms as I could. I combined any of the information I have been able to find. 

Eli and Evan Leishman were diagnosed with GM1 Gangliosidosis Type II in August 2014

There is no established cure at this point, although treatment and study is being developed to possibly slow or arrest the progression of the disease.  

What is GM1 gangliosidosis? A type of Lysosomal Storage Disorder which also falls under the categories of Genetic Brain Disorders, Inborn Errors of Metabolism and Metabolic Disorder  

It is a beta-galactosidase-1 (GLB1) enzyme deficiency.  GM1 Gangliosidosis is an inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. It is an inherited disease in which one or more enzymes in the lysosomes are defective. Lysosomes are cell's recycling centers, where proteins, fats and other molecules are broken down into their basic building blocks, which are then reused to make new molecules. Lysosomal storage diseases occur when lysosomes lack the enzymes they need to perform their recycling tasks, leading to abnormal accumulation of the molecules the lysosome is supposed to break down. 

Eli and Evan have been diagnosed with GM1 type 2, the late-infantile or juvenile type. There are 3 types of GM1 presented below, but the features can overlap significantly. Some believe GM1 to be a continuous disease spectrum instead of three distinct types. 

Symptoms of GM1 

*I starred the symptoms I've seen in my own children.

Neurologic findings  

*developmental delay, arrest and regression 

*Exaggerated startle reaction to loud noises. 

*Tonic-Clonic Seizure - generalized seizure that affects the entire brain.  

*Dementia – a loss of brain function that affects memory, thinking, language, judgment and behavior.  

*Speech delay then speech disturbance and speech loss (Type I - Infantile Types usually don't develop speech at all)

*profound intellectual disability 

*Severe psychomotor retardation -involves a slowing-down of thought and a reduction of physical movements in an individual. 

Muscular System (Often Neurologic in source)

Joint contractures - stiffness or constriction in the joints that restricts normal movement. It develops when your normally pliable connective tissues become less flexible. 

*Generalized Hypotonia (low muscle tone) initially, developing into spasticity.   

*Spasticity is stiff or rigid muscles. It may also be called unusual tightness or increased muscle tone. Reflexes (for example, a knee-jerk reflex) are stronger or exaggerated. The condition can interfere with walking, movement, or speech. 

*Muscle Weakness 

Hyperreflexia – Is defined as overactive or over-responsive reflexes. Examples of this can include twitching or spastic tendencies.

Generalized dystonia – painful muscle contractions resulting in uncontrollable distortions. It causes twisting and repetitive movements or abnormal postures.  

*Ataxia – a balance disorder, consisting of lack of voluntary coordination of  muscle movements. (Type I infantile cases are usually unable to develop the ability to sit or walk in the first place)

*Decerebrate rigidity (decerebrate response, extensor posturing) - it describes the involuntary extension of the upper extremeties in response to external stimuli. In decerebrate posturing, the head is arched back, the arms are extended by the sides, and the legs are extended.[6] A hallmark of decerebrate posturing is extended elbows.[12] The arms and legs are extended and rotated internally. 

*Growth Retardation 

Ophthalmologic findings

*Clouding of the clear outer covering of the eye (the cornea)

Loss of vision as the light sensing tissue at the back of the eye (the retina) gradually deteriorates  

cherry-red spot - about %50 develop it 

*Strabismus - Strabismus is a disorder in which the two eyes do not line up in the same direction, and therefore do not look at the same object at the same time. (Eli has had three eye surgeries to correct this, before his diagnosis)

Optic atrophy - the optic nerve, which carries impulses from the eye to the brain begins to waste away or deteriorate 

Retinal hemorrhage is a disorder of the eye in which bleeding occurs into the light sensitive tissue on the back wall of the eye. 

Blindness 

*Nystagmus is a term to describe fast, uncontrollable movements of the eyes. 

Dysmorphic features

(These features display in some infantile cases, but are usually not present with juvenile or adult)
Frontal bossing - a prominent, protruding forehead.

Depressed nasal bridge and broad nasal tip 

Large low-set ears  

Long philtrum - the skin between the nose and mouth 

Course skin, thick skin 

Gingival hypertrophy  - enlarged gums 

Macroglossia – unusually large tongue 

Hirsutism – excessive amounts of hair, broad hands and feet 

Brachydactyly - shortness of the fingers and toes. 

Facial Edema - or facial swelling  

Cardiovascular findings

Dilated and/or hypertrophic cardiomyopathy -  is a condition in which the heart becomes weakened and enlarged and cannot pump blood efficiently.  (common in Infantile Cases)

Atrial tachycardia is a type of atrial arrhythmia (faster heart rate) 

Skeletal abnormalities

*Lumbar Gibbus deformity is a form of structural kyphosis, where one or more adjacent vertebrae become wedged, producing a hump outward curviture in the lumbar region. (Eli's kyphosis in his lumbar spine was noticed by his mother a few months before he turned 3. He was prescribed a stiff body brace to wear 23 hours per day. He wore that for more than a year)

Dorso Lumbar Kyphoscoliosis - describes an abnormal curvature of the spine in both a coronal and sagittal plane. It is a combination of kyphosis and scoliosis. 

Digestive, Lymphatic and Respiratory System

Poor appetite, poor sucking in infants 

Hepatosplenomegaly (HSM) - enlarged liver and spleen 

Inguinal hernia – protrusion of abdominal cavity contents through the inguinal canal 
Umbilical Hernia - An umbilical hernia is an outward bulging (protrusion) of the abdominal lining or part of the abdominal organ(s) through the area around the belly button. 

*Swallowing disturbance,*spitting/throwing up and thicker mucous production (Started with spitting up after meals probably at least twice a day and coughing while drinking water or eating. At the beginning Eli was sent home multiple times from school because of throwing up, but he never turned out to be sick. (age 5) Then he had trouble swallowing water and would spit out at least half of the water out of the corner of his mouth while drinking. Got a feeding tube at age 6. As of 1/20/18 Eli's swallowing disturbance is including terrible choking episodes, even though he is tube fed only at this point (age 8). He has choking episodes from choking on spit up or thick saliva or secretions.)

Recurrent bronchopneumonia -  is the acute inflammation of the walls of the bronchioles.  

Reproductive System 

Swelling of the scrotum 

Other Rare symptoms

Angiokeratoma corporis diffusum (reported infrequently) also called Fabry disease 

Hydrops fetalis (has been reported) - is a serious condition in which abnormal amounts of fluid build up in two or more body areas of a fetus or newborn. 

*Prominent dermal melanocytosis (Mongolian spots) (Has been reported) - Mongolian  spots are flat, blue, or blue-gray skin markings near the buttocks that appear at birth or shortly thereafter. (I've seen mongolian spots on Evan's body much more than Eli's) 

Prognosis/Life Expectancy for GM1 Gangliosidosis

Prognosis will vary based on how aggressively parents choose to uphold life, but most sources say the following:

Type I Infantile Form

Type I is the most common form of the disease and usually becomes apparent by 6 months and can have most, if not all, of the symptoms listed above. 
Life Expectancy - Individuals with GM1 gangliosidosis Type I usually do not survive past early childhood, often succumbing during the second year of life because of infection and cardiopulmonary failure. 

*Type II Late infantile and juvenile forms

Age of Onset - Some sources I've found say age of onset for late-infantile is around 18 months of age and the age of onset for juvenile closer to 5 years. Other sources combine the two forms, late-infantile/juvenile form as having onset between 7 months and 3 years. Another source I've found completely takes out the juvenile type and describes the late infantile as having an onset typically between ages 1 and 3 years with the adult striking between ages 3 and 30. 

Symptoms -  

Type II can have all the same symptoms as Type I, but at a later onset (and with slower progression), with the exception of dysmorphic features, cherry red spots and enlarged organs which are not usually found with late-infantile and juvenile children. Common neurological symptoms include ataxia, seizures, dementia, and difficulties with speech.
Life Expectancy - Type II progresses more slowly than type I, but still causes a shortened life expectancy. People with the late infantile form typically survive into mid-childhood, (around 6-12 years) while those with the juvenile form may live into early adulthood. 

Type III or Adult onset

The third type of GM1 Gangliosidosis is known as the adult or chronic form, and it represents the mildest end of the disease spectrum. The age at which symptoms first appear varies in GM1 Gangliosidosis type III, onset generally during childhood or adolescence and by cerebellar dysfunction. 

Symptoms: The characteristic features of this type include involuntary tensing of various muscles (dystonia), abnormalities of the spinal bones (vertebrae), slowly progressive dementia, dysathria, dystonia, corneal clouding in some patients, short stature, mild vertebral anomalies and ataxia. Eye movements are normal. Angiokeratomas may develop on the lower part of the trunk of the body. Most patients have a normal size liver and spleen.  

Life expectancy varies among people with GM1 gangliosidosis type III, but a shortened life expectancy is likely.

Complications

Aspiration pneumonia - patients with G M1 gangliosidosis are at risk for aspiration pneumonia and recurrent respiratory infections resulting from neurologic compromise. 
Congestive heart failure may result secondary to cardiomyopathy.
Atlantoaxial instability Atlantoaxial instability (AAI) is characterized by excessive movement at the junction between the atlas (C1) and axis (C2) as a result of either a bony or ligamentous abnormality. Neurologic symptoms occur when the spinal cord is involved. This can develop because of abnormally shaped cervical vertebrae. If this occurs, patients should be monitored, and they eventually should undergo surgical stabilization to avoid the risk of spinal cord injury.