Paediatric Neurology Fellow University at Buffalo Buffalo, New York
Rationale: Unlike the severe form of glycine encephalopathy (NKH), the attenuated form of this disorder has greater variability in presentation. Diagnosis can be challenging, and early diagnosis is crucial since treatment can be transformative. We present a case of attenuated glycine encephalopathy in a six-month-old infant with refractory focal epilepsy and progressive encephalopathy. Methods: The infant was monitored over a period of several months. A comprehensive chart review was undertaken with review of EEG, laboratory and genetic testing. The child was examined at frequent intervals as medications were adjusted. Results: A six-month-old female of Arab-Israeli heritage was assessed in the emergency department (ED) following a new onset afebrile generalized convulsive seizure lasting five minutes. The event was preceded by a focal seizure one month prior, involving tonic-clonic movements of the right upper and lower extremities. Brain MRI was within normal limits while EEG revealed right central sharp waves. The infant was treated with levetiracetam but returned to the ED within three weeks with progressive lethargy and afebrile status epilepticus with frequent seizures originating from the right hemisphere on EEG. Seizure semiology involved behavioral arrest, eye twitching, staring spells and occasionally head deviation to the left. The infant remained lethargic with frequent seizures despite therapy with phenobarbital and oxcarbazepine. An epilepsy gene panel revealed a homozygous variant in GLDC (variant C.2T >C). Serum glycine was reported by the lab as normal at 399.2 Um/L but on close review was on high border of normative value (normal 81-436 uM). CSF glycine analysis was reported as “essentially normal”, at 56 nmol/Ml. However, review of published CSF levels suggest normal is < 20 µmol. For attenuated NKH, the range is 41-510 (average 99), vs. 40-510 range with average of 228 for severe NKH. Attenuated NKH was confirmed with a CSF/plasma glycine ratioof 0.14 (attenuated NKH average 0.13 (range 0.04-0.22), vs severe NKH 0.22 (0.09-0.45) and normal values≤ 0.02). Treatment was initiated with sodium benzoate and dextromethorphan, and the infant was seen regularly in follow up. Since starting treatment, she has remained seizure-free for 6 months and parents report significant improvement in levels of alertness and development. Repeated EEG have normalized. Conclusions: The diagnosis of the attenuated form of infantile glycine encephalopathy can be challenging. Initial presentation can be non-specific and preliminary work-up unrevealing. CSF analysis may not be diagnostic as the levels were reported by our lab as essentially normal. In this case the infant presented with catastrophic localization related epilepsy, and while workup for epilepsy surgery was contemplated, the comprehensive genetic panel was crucial in obtaining an accurate diagnosis and lifesaving therapy. We conclude that a comprehensive gene panel should be performed for all infants with challenging epilepsy, including infants presenting with localization related seizures. Funding: Please list any funding that was received in support of this abstract.: No funding was received in support of this study.