ALG6-CDG in South Africa: Genotype-Phenotype Description of Five Novel Patients

Dercksen, Marli; Crutchley, Anthony C; Honey, Engela; Lippert, M; Matthijs, Gert; Mienie, Lodewyk J.; Schuman, H; Vorster, Barend C.; Jaeken, Jaak

doi:10.1007/8904_2012_150

Cited by 16 publications

(18 citation statements)

References 21 publications

(45 reference statements)

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“…From this cohort, 35 patients have never been reported, and six were recently reported but the authors offered follow-up data (Al-Owain et al 2010;Dercksen et al 2013). Six patients with insufficient data (no availability of results of mutation analysis but with type I TIEF profile and characteristic LLO abnormalities for ALG6) were excluded from the genotype-phenotype analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Due to the presence of common mutations in ALG6-CDG, the genotype-phenotype correlation was analyzed by dividing the patients into three groups: p.A333V homozygous patients, p.A333V compound heterozygous patients, and patients homozygous for a severe mutation. A mutation was labeled a priori as severe according to previously reported severe or deleterious phenotypic expression and according to type and localization of the mutation in the ALG6 gene (Dercksen et al 2013).…”

Section: Methodsmentioning

confidence: 99%

“…Patients with these mutations were described with a phenotype of hypotonia, speech disability, and epilepsy (Lefeber et al 2011). So far, its clinical course and progression is reported in 48 ALG6-CDG patients showing severe psychomotor retardation, seizures, speech disability, some dysmorphic symptoms, and variable presence of failure to thrive, gastrointestinal features, hormonal anomalies, coagulopathy, and elevated transaminase activities (AlOwain et al 2010;Dercksen et al 2013;Drijvers et al 2010;Ichikawa et al 2013;Lefeber et al 2011;Miller et al 2011). Unique features, such as abnormal skeletal development and short fingers, have been described in two ALG6-CDG patients, suggesting a possible association between skeletal development and the primary glycosylation defect (Drijvers et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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ALG6‐CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies

Morava

Tiemes

Thiel

et al. 2016

J of Inher Metab Disea

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Introduction Alpha-1,3-glucosyltransferase congenital disorder of glycosylation (ALG6-CDG) is a congenital disorder of glycosylation. The original patients were described with hypotonia, developmental disability, epilepsy, and increased bleeding tendency.Methods Based on Euroglycan database registration, we approached referring clinicians and collected comprehensive data on 41 patients. Results We found hypotonia and developmental delay in all ALG6-CDG patients and epilepsy, ataxia, proximal muscle weakness, and, in the majority of cases, failure to thrive.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ALG6‐CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies

Morava

Tiemes

Thiel

et al. 2016

J of Inher Metab Disea

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“…Cerebellar involvement on imaging has been reported in only four patients. 85,86 ALG8-CDG ALG8-CDG (glucosyltransferase 2 deficiency) has been reported in 10 patients with variable neurologic, intestinal, and hepatic involvement. No functional or imaging cerebellar involvement has been reported, but in one patient cerebellar atrophy was found at autopsy.…”

Section: Alg6-cdgmentioning

confidence: 99%

Congenital Disorders of Glycosylation with Emphasis on Cerebellar Involvement

2014

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Congenital disorders of glycosylation (CDG) are genetic diseases due to defective glycosylation of proteins and lipids. The authors present an update on these disorders affecting the central nervous system with a focus on cerebellar involvement. The rate of identification of novel CDG shows an exponential increase. Some 76 CDG are actually known, not taking into account the defects in glycan-modifying proteins. Neurologic involvement is present in the large majority of CDG. Screening methods are limited to serum transferrin isoelectrofocusing (for N-glycosylation disorders with sialic acid deficiency), and serum apolipoprotein C-III isoelectrofocusing (for core 1 mucin-type O-glycosylation disorders). Whole exome/genome sequencing is increasingly used in the diagnostic workup of patients with CDG-X. Treatment is greatly lagging behind because only one CDG is efficiently treatable (MPI-CDG). Cerebellar involvement is an important feature of PMM2-CDG, the congenital muscular dystrophies due to dystroglycanopathy, and SRD5A3-CDG. It has also been reported in some patients with ALG1-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, ALG8-CDG, PIGA-CDG, DPM1-CDG, DPM2-CDG, B4GALT1-CDG, SLC35A2-CDG, COG1-CDG, COG5-CDG, COG7-CDG, and COG8-CDG.

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“…The majority of the 54 ALG6-CDG patients published so far (Haeuptle and Hennet, 2009;Ishikawa et al, 2009;Dercksen et al, 2012;Fiumara et al, 2016;Jaeken et al, 2015) (Sun et al, 2005;Ishikawa et al, 2009;Al-Owain et al, 2010;Dercksen et al, 2012;Fiumara et al, 2016) also describe "severe epilepsy", febrile seizures, generalized seizures, complex partial seizures, atonic and myoclonic seizures, as well as generalized tonicclonic seizures. EEG is, in some children, reported as "abnormal" (Dercksen et al, 2012), but not further detailed. Overall, in the literature, many different seizure types in ALG6-CDG patients are reported, but epileptic spasms have not been described so far.…”

Section: Discussionmentioning

confidence: 99%

Epileptic spasms in congenital disorders of glycosylation

Pereira

Bahi‐Buisson

Barnérias³

et al. 2017

Epileptic Disorders

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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]

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ALG6-CDG in South Africa: Genotype-Phenotype Description of Five Novel Patients

Abstract: ALG6-CDG (formerly named CDG-Ic) (phenotype OMIM 603147, genotype OMIM 604566), is caused by defective endoplasmic reticulum a-1,3-glucosyltransferase (E.C 2.4

Cited by 16 publications

References 21 publications

ALG6‐CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies

ALG6‐CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies

Congenital Disorders of Glycosylation with Emphasis on Cerebellar Involvement

Epileptic spasms in congenital disorders of glycosylation

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