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Thursday, October 2, 2014

Exhaustive list of GM1 Symptoms

Below is a document I have made to bring to various doctors and therapists we meet with. This will quickly educate them on Eli and Evan's condition as well as any symptoms they have and will manifest in the future. I thought I would share it with you as well. I tried to make it as comprehensive with regards to possible symptoms as I could. I combined any of the information I have been able to find. 


GM1 Gangliosidosis Type II
Eli and Evan Leishman were diagnosed in August 2014
Visit our blog for updates: gm1gangliosidosis.blogspot.com

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. 

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. 

I have put a star* next to any symptoms that Eli currently has. I also put a question mark ? next to symptoms he may have to a small degree or is beginning to develop. Eli is 5 years old and was born in  March 2009. 
Evan (age 2, born Aug. '12) has so far been affected by strabismus, speech delay, clumsiness and is slightly below average in development for his age.

Type I  - Infantile form – usually becomes apparent by 6 months.  
Signs and Symptoms listed from various resources 

Neurologic findings  
*developmental delay, arrest and regression (Eli was delayed at 18 months-2 years, followed by arrest and regression)
?Exaggerated startle reaction to loud noises. (Eli has begun to get overly startled by 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 (Eli's speech developed to a below average 18 month old levels ability, then regressed to a few sounds, Mmm, aah, dah and some gutteral noises. He still plays with sound, but it is unclear)
*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. (Eli seems very stiff, it takes work to manipulate his body sometimes)
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 (Eli gets tired easily. His muscles can't handle walking for too long, even when using his walker. We had to start sending his stroller to school along with his walker because he couldn't handle walking from the bus to his classroom each day. It was too exhaustive for him)
Hyperreflexia – Is defined as overactive or overresponsive reflexes. Examples of this can include twitching or spastic tendencies. It may lead to seizures, stroke and even death. 
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. (Poor balance was the first symptom we noticed with Eli at age 12 months, it has gradually worsened over time. His knees, head and area around his eyes are scarred from falling so often. He never gives up, just keeps getting back up. He received a protective helmet, Jan. 2014, it was long overdue!)                   
*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. (Eli is beginning to use this posture, his head is almost always tilted back with arms and elbows out. He extends his legs stiffly when moved)
*Growth Retardation (Eli didn't grow at all from age 4 to 5, height wise, at least that's what was recorded at his pediatric appointments. He probably did grow, just a small amount. He also thinned out a lot during that time period. He does look a bit longer to me now, so I think he is growing. But he is much shorter than most children his age)
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  (Eli seems to have continued worsening of his eyes/prescription over time)
cherry-red spot - about %50 develop it 
*StrabismusStrabismus 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, his eyes are aligned pretty well when he's focusing, but still drift often)
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 retensitive 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, usually not present with juvenile or adult forms)              
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. 
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 and now wears it only at night, because the brace is too dangerous to wear while trying to walk because of his poor balance and constant falling)
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 (Eli will spit up after meals probably at least twice a day. This spit up is often thick. He has been sent home multiple times from school because of throwing up, but he never turned out to be sick. He has also begun to have trouble swallowing water and will spit out at least half of the water out of the corner of his mouth while drinking)
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.   

Type II Late infantile and juvenile forms
Some sources I've found say age of onset around the age of 18 months for late-infantile and 5 years for juvenile. 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 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 could have the same symptoms as Type I 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. Neurological symptoms include ataxia, seizures, dementia, and difficulties with speech.


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.  

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.


Prognosis for GM1 Gangliosidosis
Prognosis will vary based on how aggressively parents choose to uphold life and search for cutting edge treatments as well as variance within each type, but most sources say the following:
Individuals with GM1 gangliosidosis - type I usually do not survive past early childhood,often during the second year of life because of infection and cardiopulmonary failure.  
Type II usually 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. 
Life expectancy varies among people with GM1 gangliosidosis type III, but a shortened life expectancy is likely.