Epilepsy in Biotinidase Deficiency Is Distinct from Early Myoclonic Encephalopathy

Myoclonic encephalopathy in neonates mainly consists of early myoclonic encephalopathy(EME) that combines erratic myoclonus of face and extremities with suppression bursts on electroencephalogram (EEG). This metabolic or genetic condition bears poor prognosis,[1] with an exception, pyridoxine-dependent epilepsy.[2] Here, we show that clinical and EEG features of early onset epilepsy caused by biotinidase deficiency are distinct from EME.

Following normal initial development, a 2.6-month-old male infant presented with frequent jerks from the second month of life, loss of visual contact, smile and head control, and fragmented EEG tracing ([Fig. 1A]). However, in contrast with EME, video-EEG showed that bursts mostly comprised slow waves with a few spikes but no polyspikes and no jerks, whereas jerks were due to clonic seizures ([Fig. 2B]). Pyridoxine, thiamine, and hydrocortisone failed. Recurrent so-called conjunctivitis ([Fig. 1C]), peeling skin ([Fig. 1D]), and very high lactate (4.1–10.5mmole/L) levels pointed to biotinidase deficiency (0.10U/L) with a homozygous previously reported mutation. First week on biotin (40 mg/kg/d), seizures disappeared, lactate normalized, and EEG turned to multifocal spikes ([Fig. 2A]) before normalizing totally ([Fig. 2B]).

Fig. 1 (A) Discontinuous electroencephalogram in sleep with burst of bilateral high-voltage (up to 260 mV) irregular spikes and slow waves. (B) Clonic seizure. Burst of diffuse, bilateral, rhythmic spike-and-waves. (C) So-called conjunctivitis. (D) Peeling skin with hair loss.

Fig. 2 (A) Continuous background activity with multifocal epileptiform activity (6th day on biotin treatment). (B) Normal electroencephalogram (6 months after biotin treatment initiating).

Biotinidase deficiency was repeatedly reported as a cause of EME but EEG records were not provided.[3] [4] Our clinical and EEG report shows that the clinical and EEG pattern of epilepsy in biotinidase deficiency is distinct from EME, and this distinction should permit early diagnosis and specific treatment. In contrast with excessive N-methyl-d-aspartate transmission of EME explaining the polyspikes,[2] [5] biotin deficiency alters Krebs cycle with both excessive gamma-aminobutyrate and N-methyl-d-aspartate neurotransmissions, with increased slow waves and spikes, explaining the distinct electroclinical pattern that we report.[6]

Disclosure

The authors declared that this study has received no financial support.

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