Further Delineation of the ALG9-CDG Phenotype

Alsubhi, Sarah; Alhashem, Amal; Alazami, Anas M.; Tlili, Kalthoum; AlShahwan, Saad; Lefeber, Dirk; Alkuraya, Fowzan S.; Tabarki, Brahim

doi:10.1007/8904_2015_504

Cited by 17 publications

(12 citation statements)

References 14 publications

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“…Delayed myelination is a consistent finding on neuroimaging of the published patients [1] , [12] . This was also seen in our patient.…”

Section: Discussionsupporting

confidence: 77%

“…This was also seen in our patient. Global cerebral and cerebellar atrophy was a consistent finding in all the published patients with brain MRI [1] , [12] . Like in many genetic and neurometabolic syndromes, cerebral atrophy may not present in early stages of the disease but on follow-up MRI of our patient at 25 months, cerebral atrophy was present.…”

Section: Discussionsupporting

confidence: 74%

“…The two females and one male were from different consanguineous Middle Eastern families and were homozygous for NG_009210.1: g.(35929T > A), NM_024740.2: c.(1173 + 2T > A); the authors suggested the possibility of a founder mutation as one potential explanation. In 2015, another four related patients with ALG9-CDG were reported by AlSubhi et al [1] . The patients were part of a large, consanguineous Saudi Arabian family and were homozygous for the mutation also reported by Frank et al [4] , c.(1588G > A), p.(E530K).…”

Section: Introductionmentioning

confidence: 93%

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ALG9-CDG: New clinical case and review of the literature

Davis

Webster

Smith

et al. 2017

Molecular Genetics and Metabolism Reports

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Congenital disorders of glycosylation (CDG) are a group of metabolic diseases resulting from defects in glycan synthesis or processing. The number of subgroups and their phenotypic spectrums continue to expand with most related to deficiencies of N-glycosylation. ALG9-CDG (previously CDG-IL) is the result of a mutation in ALG9. This gene encodes the enzyme alpha-1,2-mannosyltransferase. To date, a total of 10 patients from 6 different families have been reported with one of four ALG9 mutations. Seven of these patients had a similar phenotype with failure to thrive, dysmorphic features, seizures, hepatic and/or renal cysts; the other three patients died in utero from a lethal skeletal dysplasia. This report describes an additional patient with ALG9-CDG who has a milder phenotype. This patient is a term female born to Caucasian, Canadian, non-consanguineous parents of Scottish decent. Prenatally, dysmorphic features, numerous renal cysts and minor cardiac malformations were detected. Post-natally, dysmorphic features included shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata. She developed failure to thrive and seizures. The metabolic work-up included analysis of a transferrin isoelectric focusing, which showed a type 1 pattern. This was confirmed by glycan profiling, which identified ahomozygous mutation in ALG9, c.860A > G (p.Tyr287Cys) (NM_1234567890). This had been previously published as a pathogenic mutation in two Canadian patients. Our goal is to contribute to the growing body of knowledge for this disorder by describing the phenotypic spectrum and providing further insight on prognosis.

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“…Delayed myelination is a consistent finding on neuroimaging of the published patients [1] , [12] . This was also seen in our patient.…”

Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 93%

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ALG9-CDG: New clinical case and review of the literature

Davis

Webster

Smith

et al. 2017

Molecular Genetics and Metabolism Reports

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“…It has been proposed that the interaction of ALG9 with ALG12 is required for the ultimate formation of the disaccharide glycan, which influences further downstream processing of N-glycans, indicating a potential regulatory role for the ALG9 gene in glycosylation (Coss et al 2014). The clinical phenotype for ALG9-CDG has recently been expanded (see Table 1) (AlSubhi et al 2016).…”

Section: Abnormal Gene Expression and Cell Signaling In Galactosaemiamentioning

confidence: 99%

Classical Galactosaemia and CDG, the N-Glycosylation Interface. A Review

et al. 2016

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Classical galactosaemia is a rare disorder of carbohydrate metabolism caused by galactose-1-phosphate uridyltransferase (GALT) deficiency (EC 2.7.7.12). The disease is life threatening if left untreated in neonates and the only available treatment option is a long-term galactose restricted diet. While this is lifesaving in the neonate, complications persist in treated individuals, and the cause of these, despite early initiation of treatment, and shared GALT genotypes remain poorly understood. Systemic abnormal glycosylation has been proposed to contribute substantially to the ongoing pathophysiology. The gross N-glycosylation assembly defects observed in the untreated neonate correct over time with treatment. However, N-glycosylation processing defects persist in treated children and adults.Congenital disorders of glycosylation (CDG) are a large group of over 100 inherited disorders affecting largely N-and O-glycosylation.In this review, we compare the clinical features observed in galactosaemia with a number of predominant CDG conditions.We also summarize the N-glycosylation abnormalities, which we have described in galactosaemia adult and paediatric patients, using an automated high-throughput HILIC-UPLC analysis of galactose incorporation into serum IgG with analysis of the corresponding N-glycan gene expression patterns and the affected pathways.

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“…Delayed myelination and cerebellar atrophy are frequently reported in ALG-9 CDG. 5 Index child was atypical in having a normal MRI brain. However, initial normal MRI brain with progressive development of atrophy has been reported in this entity.…”

Section: Discussionmentioning

confidence: 99%