Asparagine Synthetase Deficiency is a rare hereditary disorder that presents during the neonatal period or infancy. It is associated with early death.
Chromosome: 7q21.3
Gene affected: ASNS
Gene product: asparagin synthetase (glutamine hydrolyzing)
Inheritance: autosomal recessive
Triad:
(1) congenital microcephaly
(2) severe global developmental delay
(3) axial hypotonia followed by spastic quadraplegia, seizures, jitteriness and hyperekplexia
Other clinical findings:
(1) intrauterine growth restriction
(2) failure to thrive
(3) feeding difficulties
(4) short stature
(5) cortical blindness
(6) hearing loss
(7) apnea
(8) variable dysmorphic facial features (telecanthus, big fleshy ears, prominent nasal tip, micrognathia, sloping forehead, brachycephaly)
MRI of the brain may show:
(1) generalized brain atrophy
(2) simplified gyral pattern
(3) hypoplasia of the cerebellar vermis
Laboratory findings:
(1) undetectable or low CSF asparagine concentration
(2) variable plasma asparagine (may be normal or low)
(3) normal urine organic acids
Diagnosis is based on identifying appropriate gene mutations.
