Abstract
Asparagine synthetase (ASNS) deficiency is a rare inborn error of metabolism caused
by a defect in ASNS—a gene encoding asparagine synthetase. It has mainly been described
as a neurological phenotype manifesting as severe developmental delay, congenital
microcephaly, spasticity, and refractory seizures; it is not associated with any specific
dysmorphisms. ASNS deficiency leads to the inability to synthesize a nonessential
amino acid in the brain, this explains why the symptoms are primarily neurological.
The accumulation of aspartate/glutamate causes increased neuronal apoptosis leading
to brain atrophy and increased neuronal excitability leading to seizures. Asparagine
levels in plasma and cerebrospinal fluid are not reliable biomarkers for this disorder,
therefore diagnosis is mainly obtained by molecular genetics. This disorder is associated
with a poor prognosis and there is no treatment except supportive therapy. Prenatal
diagnosis is possible. We report a case of a later onset form, c.146G > A (p.Arg49Gln)
variant in the ASNS gene detected by molecular analysis using next-generation sequencing;
the patient's clinical presentation included microcephaly, regression of developmental
milestones, epilepsy, and hyperthermia.
Keywords
asparagine synthetase deficiency - microcephaly - epilepsy - developmental delay
