Alpha-N-Acetylgalactosaminidase Deficiency Type 1

A very rare and severe type of NAGA deficiency characterized by infantile neuroaxonal dystrophy.

Epidemiology

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

Clinical description

The disease presents with psychomotor retardation at around 9 months of age and later, at the age of 2, with developmental retrogression. Further manifestations follow between the ages of 4-10 years, including muscular hypotonia, spasticity, nystagmus, strabismus, myoclonic jerks, grand-mal seizures, cortical blindness and deafness, optic and brain atrophy, loss of environmental contact and decorticate posturing. No visceromegaly or coarsening of features has been reported.

Etiology

NAGA deficiency type 1 is caused by a homozygous NAGA gene (22q13.2) mutation resulting in a Glu325-to-Lys (E325K) substitution and the dysfunction, instability and rapid degradation of the lysosomal protein NAGA.

Genetic counseling

Transmission is autosomal recessive and genetic counseling is possible.