Alpha-N-Acetylgalactosaminidase Deficiency Type 3

A rare clinically heterogeneous type of NAGA deficiency with developmental, neurologic and psychiatric manifestations presenting at an intermediate age.

Epidemiology

Prevalence of this disorder is not known but less than 20 cases have been reported to date for NAGA deficiency

Clinical description

A very wide spectrum of signs, with a juvenile onset, has been described including asymptomatic patients at the time of diagnosis. Manifestations seen in clinically overt cases may include epilepsy of variable severity, psychomotor retardation, intellectual impairment, autism, strabismus and cataract.

Etiology

Compound heterozygous or homozygous mutations of the alpha-N-acetylgalactosaminidase gene (NAGA; 22q13.2) have been reported in affected patients but also occasionally in their healthy siblings. These mutations lead to the dysfunction, instability and rapid degradation of the lysosomal protein NAGA.

Genetic counseling

Transmission is autosomal recessive and genetic counseling is possible.