Epileptic spasms in congenital disorders of glycosylation

Abstract

Aim. Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, characterized by impaired glycosylation. Multisystemic involvement is common and neurological impairment is notably severe and disabling, concerning the central and peripheral nervous system. Epilepsy is frequent, but detailed electroclinical description is rare. Methods. We describe, retrospectively, the electroclinical features in five children with CDG and epileptic spasms. Results. Epileptic spasms were observed in patients with ALG1‐, ALG6, ALG11‐CDG and CDG‐Ix, and occurred at an early age, before 6 months in all cases, except one who had spasms that started at 18 months. In this patient, spasms had an unusual aspect; they did not occur in clusters and were immediately preceded by a myoclonus. All but one child also presented rare myoclonias. On EEG, background activity was poorly organized with abundant posterior spike and fast rhythm activity, but without hypsarrhythmia. At the last evaluation (age range: 6–12 years), two patients still presented epileptic spasms and subcortical myoclonias, one showed rare generalized tonic‐clonic seizures, and two were seizure‐free. Conclusion. CDG disorders can be associated with epileptic spasms showing particular features, such as absence of hypsarrhythmia, posterior EEG anomalies, and an unusual combination of epileptic spasms with myoclonus. These features, associated with pre‐existing developmental delay and subcortical myoclonias, may shift toward CDG screening. [Published with video sequence and supplemental EEG plates on http://www.epilepticdisorders.com]

West syndrome: a comprehensive review

“…ISs have been also reported in children with neurodegenerative disorders including globoid cell leukodystrophy-Krabbe disease (caused by the GALC gene) and Menkes disease (caused by the ATP7A gene) [58][59][60]. Rare disorders associated with ISs also include cerebrotendineous xantomatosis (caused by the CYP27A1 gene) [61]; glucose transport 1 deficiency (caused by mutations in exon 9 of the SLC2A1 gene) [62]; disorders of glycosylation [63] (caused by the ALG1,6,11 genes: subtypes CDG and CDG 1x). Pyridoxine-dependent epilepsy (PDE) may present with various types of severe seizures, partial and generalized seizures, atonic and myoclonic seizures, convulsive status epilepticus, and ISs [64,65].…”

ALG11‐CDG syndrome: Expanding the phenotype

“…All the previously reported ALG11‐CDG patients have epilepsy. A recent paper by Pereira (Pereira et al, ) describes that CDG can be associated with epileptic seizures showing particular features, such as absence of hypsarrhythmia, posterior EEG anomalies, and an unusual combination of epileptic seizures with myoclonus. Their patient with ALG11‐CDG presented with typical epileptic seizures that were either in very long‐lasting clusters or isolated, but also had focal clonic seizures and rare isolated massive jerks with a combination of myoclonus and spasm.…”

“…To date, only 10 patients have been described with ALG11‐CDG (OMIM# 613661) (Al Teneiji et al, ; Pereira et al, ; Regal et al, ; Rind et al, ; Thiel et al, ). We report two additional unrelated patients to expand the ALG11‐CDG phenotype to include normal transferrin glycosylation as determined by mass spectrometry in one individual, together with functional studies supporting the pathogenicity of their novel ALG11 mutations.…”

A Case of ALG6-CDG with Explosive Onset of Intractable Epilepsy During Infancy

“…Pereira et al reported a case of ALG6-CDG with epileptic spasms and generalized tonic-clonic seizures (onset at age 6 months) without hypsarrhythmia (but with abundant posterior interictal spikes and sharp waves). 13 …”

“…Pereira et al reported a case of ALG6-CDG with epileptic spasms and generalized tonic-clonic seizures (onset at age 6 months) without hypsarrhythmia (but with abundant posterior interictal spikes and sharp waves). 13 To date, there are less than 100 ALG6-CDG cases reported in the literature. All share the phenotype of hypotonia and developmental delay, and the majority (perhaps >70%) have seizures, 12 but a minority have medically intractable epilepsy.…”