Currently, at least three different diseases are known to be caused by mutations in the ATP1A1 gene. All the ATP1A1-related disorders are inherited with autosomal dominant fashion.
One is a sensory-motor axonal peripheral neuropathy, which is a condition resulting from damage of the motor and sensory nerves located outside of the brain and spinal cord (i.e., peripheral nerves) often causing distal (i.e., of the feet and, in less percentage, of the hands) weakness and muscular atrophy (i.e., the wasting or thinning of muscle mass), numbness and neuropathic pain. This condition, classified as Charcot-Marie-Tooth type 2D (CMT2DD), has variable age of onset and first signs and symptoms can begin from late childhood to fifties; the progression of signs and symptoms is described as slow over time.
A second condition is characterized by early-onset (i.e., 6 days-6 months of life) generalized tonic-clonic epileptic seizures that can long-lasting (i.e., status epilepticus), severe hypomagnesemia (i.e., low level of blood magnesium) due to renal magnesium wasting, episodes of hypokalemia (i.e., low level of blood potassium) and delay in acquisition of motor and cognitive milestones,
Finally, a third condition has been more recently described in association with ATP1A1 mutation and it consist in a neurodevelopmental syndrome (i.e., a disease that affects the development of the central nervous system leading to abnormal brain function). The few children described share a variable combination of intellectual disability, spasticity (i.e., increased muscular tone), peripheral neuropathy, sleep disturbances, and epileptic seizures.
ATP1A1