ATP1A1

Clinical Characteristics

Currently, the ATP1A1-related disorders may be differentiated according to the specific clinical features:
1.    Charcot-Marie-Tooth type 2D (CMT2DD; axonal-to-intermediate sensory and motor peripheral neuropathy with variable age of onset, ranging from late childhood to fifties, and slow progression):
•    Pes cavus
•    Distal muscle weakness and atrophy
•    Muscle cramps
•    Reduced/absent deep tendon reflexes
•    Steppage gait
•    Foot drop
•    Atrophy of the intrinsic hand muscles
•    Lower limbs more affected than upper limbs
•    Decreased vibratory sensation

2.    Hypomagnesemia, intractable seizures, severe intellectual disability (HOMGSMR2):
•    Severe renal magnesium wasting causing hypomagnesemia
•    Renal potassium wasting causing hypokalemia
•    Polyuria
•    Medullary hyperechogenicity compatible with nephrocalcinosis
•    Epilepsy with generalized tonic-clonic seizures and episodes of status epilepticus
•    Global developmental delay
•    Behavioral manifestations (autism spectrum disorder, self-beating, hyperactivity)
•    Brain abnormalities at neuroimaging (volume loss, incomplete myelination)

3.    Early-onset complex neurodevelopmental syndrome:
•    Intellectual disability
•    Spasticity/Spastic paraparesis
•    Peripheral, motor predominant neuropathy
•    Sleep disturbances
•    Epilepsy
•    Behavioral manifestations (autism spectrum disorder, self-beating, hyperactivity)