Rationale: Asparagine synthetase deficiency (ASNSD) refers to a congenital metabolic abnormality caused by mutation in the asparagine synthetase (ASNS) gene encoded by chromosome 7q21. Herein, we report the first case of ASNSD in China, in which novel ASNS mutations were identified.
Patient concerns: A 6-month-old boy presented with a 4-month history of microcephaly and psychomotor developmental retardation and a 2-month history of epilepsy. Four months after birth, magnetic resonance imaging demonstrated a giant cyst in the right lateral ventricle, and a ventriculoperitoneal shunt was placed. Video electroencephalography showed a hypsarrhythmia pattern with a string of tonic-clonic and myoclonic seizures. On admission, physical examination showed microcephaly. Neurologic examination showed a decreased tension in the trunk muscles and an increased tension in the extremity muscles; tendon hyperreflexia was noted, and bilateral pathologic reflexes were positive.
Diagnosis: A diagnosed of congenital microcephaly was made. Whole-exome sequencing revealed a heterozygous deletion mutation c.666_667delCT (p.L2221Lfs*5) in exon 6 of the ASNS gene and a heterozygous missense mutation c.1424C>T (p.T457I) in exon 13 of the ASNS gene.
Interventions: After admission, intravenous adrenocorticotropic hormone and oral topiramate was administrated for 4 weeks, while the seizures persisted. Then, levetiracetam and clonazepam were added.
Outcomes: After the follow-up period of 18 months, video electroencephalography showed that complex episodes disappeared with changes in multiple focal spike and sharp waves; 1 focal attack arising from the left occipital region and 2 focal attacks arising from the right middle temporal and the right occipital region were recorded.
Lessons: This is the first case of ASNSD in China. We identified 2 novel mutations (c.666_667delCT and c.1424C>T) in the ASNS gene, which expands the ASNS gene mutation profile and will be beneficial for genetic diagnosis.