Glossary

AADC Deficiency (AADC-d) is a rare central nervous system disorder arising from reductions in the enzyme aromatic L-amino acid decarboxylase (AADC) that result from mutations in the dopa decarboxylase (DDC) gene. This reduction leads to deficits in the neurotransmitter’s dopamine, norepinephrine, epinephrine, serotonin, and melatonin. AADC-d causes severe developmental delays, the inability to develop any motor strength and control (global muscular hypotonia/dystonia) resulting in breathing, feeding, and swallowing problems, frequent hospitalizations, and the need for life-long care. Patients with severe forms often die in the first decade of life due to profound motor dysfunction, autonomic abnormalities, and secondary complications such as choking, hypoxia, and pneumonia. No treatment options other than palliative care currently exist for many AADC-d patients.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their demise. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. When voluntary muscle action is progressively affected, people may lose the ability to speak, eat, move, and breathe. There is no cure for this fatal disease.

Diffuse interstitial pontine glioma (DIPG) is a rare, rapidly fatal pediatric brain tumor. Patients are usually diagnosed between 5-6 years of age. 98% of patients die within two years of diagnosis.

Duchenne muscular dystrophy (DMD) is the most common and one of the most severe types of muscular dystrophy. DMD occurs when a mutation in the dystrophin gene prevents the cell from making a functional dystrophin protein. Dystrophin is a muscle membrane associated protein and is critical to the structural and membrane stability of muscle fibers in the skeletal, diaphragm and heart. The absence of normally functioning dystrophin results in muscle fragility, such that muscle injury occurs when muscles contract or stretch during normal use. As muscle damage progresses, connective tissue and fat replace muscle fibers, resulting in inexorable muscle weakness. Patients with DMD typically lose walking ability by their early teens, require ventilation support in their late teens and, eventually, die due to heart and lung failure. The average age of death for DMD patients is in their mid-twenties.

Friedreich ataxia (FA) is an inherited neuromuscular disorder most commonly caused by a single genetic defect in the FXN gene that leads to reduced production of frataxin, a mitochondrial protein that is important for cellular metabolism and energy production. FA results in a physically debilitating, life-shortening condition and is the most common hereditary ataxia. Symptoms of FA include progressive loss of coordination and muscle strength, which lead to the full-time use of a wheelchair; scoliosis (which often requires surgical intervention); diabetes mellitus; hearing and vision impairment; serious heart conditions; and premature death. Current FA therapies are primarily focused on symptom relief, and there are no FDA-approved drugs to treat the cause of FA.

Familial Chylomicronemia Syndrome (FCS) is an ultra-rare disease caused by impaired function of the enzyme lipoprotein lipase (LPL) and characterized by severe hypertriglyceridemia (>880mg/dL) and a risk of unpredictable and potentially fatal acute pancreatitis. Because of limited LPL function, people with FCS cannot breakdown chylomicrons, lipoprotein particles that are 90% triglycerides. FCS patients are also at risk of chronic complications due to permanent organ damage. They can experience daily symptoms including abdominal pain, generalized fatigue and impaired cognitions that affect their ability to work. People with FCS report major emotional and psychosocial effects including anxiety, social withdrawal, depression, and brain fog. There is no effective therapy for FCS currently available.

Hereditary transthyretin (hATTR) amyloidosis is a progressive, systemic, and fatal inherited disease caused by the abnormal formation of the TTR protein and aggregation of TTR amyloid deposits in various tissues and organs throughout the body, including in peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid, and bone marrow. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads to sensory, motor, and autonomic dysfunction often having debilitating effects on multiple aspects of a patient’s life. Ultimately, hATTR amyloidosis results in death within three to 15 years of symptom onset. Therapeutic options for the treatment of patients with hATTR amyloidosis are limited.