Abstracts

Rationale: ALG11-Congenital Disorder of Glycosylation (ALG11-CDG) is a rare inborn error of metabolism associated with epilepsy and intellectual disability. We describe a case with severe drug-resistant epilepsy with a characteristic burst-suppression pattern on EEG and partial response to Topiramate.


Methods: Case report.

Results: A 3.5 month baby girl presented with clusters of tonic seizures in the context of bronchiolitis. Parents reported a 3 day history of episodes of eye rolling and tonic spasms of her shoulders and upper limbs. On examination, she had axonal hypotonia, wandering eye movements, microcephaly and head lag. Initial EEG showed multi focal epileptiform discharges on a high amplitude background with a number of brief tonic seizures associated with attenuation and overriding fast activity (Figure 1). Seizures continued despite treatment with prednisolone, vigabatrin, levetiracetam, sodium valproate and ketogenic diet and were almost continual when awake.



MRI brain showed delayed myelination for age. Biochemical investigations included Isoelectric focussing (IEF) of transferrin, which showed a Type 1 CDG pattern. Other blood and CSF biochemistry was normal.Expedited trio whole genome sequencing showed compound heterozygous likely pathogenic variants in the ALG 11 gene, c.1037G >A p.(Arg346His) and c.555T >A p.Phe185Leu, consistent with a diagnosis of Type1-p CDG or ALG11-CDG.





Further EEG showed striking periods of background attenuation or suppression approximating a burst-suppression pattern (Figure 2). .

Previous case reports of children with ALG11-CDG have reported epilepsy and developmental phenotypes of varying severity (Haanpää et al., 2019). Regal et al (Regal et al., 2015) reported one child with early onset drug resistant epilepsy and severe developmental delay who had a similar persistent burst suppression pattern on EEG. With the introduction of Topiramate there was a reduction in seizure duration and clustering and less requirement for emergency medication. Currently she has some awake period which are seizure free though developmental progress has been minimal.


Conclusions: ALG11-CDG is a rare inherited inborn error of metabolism due to abnormal protein and lipid glycosylation that can cause severe infantile epilepsy and developmental delay. A unusual burst suppression pattern has been reported in 2 cases, both of which have had some clinical and electrographic response to topiramate. This study adds to the understanding of EEG abnormalities in ALG11-CDG and consideration should be given to this condition in cases with similar clinical and electrographic features. Topiramate may be a helpful therapeutic option.

Funding: None