ALG1-CDG: A Patient with a Mild Phenotype and Literature Review

Abstract

ALG1-congenital disorder of glycosylation (ALG1-CDG) is an autosomal recessive multisystem disease. We here present a patient with a mild phenotype of ALG1-CDG. A 15-month-old female was referred with hypotonia, failure to thrive, and developmental delay. At 8 months of age, failure to thrive, feeding difficulties and developmental delay became apparent, and an epileptic seizure was observed at 11 months of age. Progressive deterioration and swallowing difficulty were observed. A brain MRI revealed a widening of the cerebrospinal fluid spaces and ventricular system, and decreased protein C, protein S and antithrombin III levels were identified. The isoelectric focusing showed a type 1 pattern. A homozygous c.1076C>T (p.Ser359Leu) variant was found in the <i>ALG1</i> gene. CDG should be taken into consideration in patients presenting with unexplained multisystem involvement.

Perinatal manifestations of congenital disorders of glycosylation—A clue to early diagnosis

“…The group of congenital disorders of N-glycosylation consists of at least 31 diseases, with different enzyme or transporter deficiencies, which lead to a similar pathophysiological effect: defect of synthesis and/or processing of glycoproteins and glycolipids ( Abu Bakar et al, 2018 ). Some types of CDGs have their distinctive features, but there is still a pool of symptoms that are common for a majority of N-glycosylation CDGs and some of the mixed glycosylation disorders involving the N-glycosylation pathway, like psychomotor retardation, hypotonia, peripheral neuropathy, stroke-like episodes, nephrotic syndrome, failure to thrive, nystagmus, strabismus, retinitis pigmentosa, third space effusions, cardiomyopathy, liver disease, or microcystic kidneys presenting as hyperechogenic in ultrasonography (USG) ( Hertz-Pannier et al, 2006 ; Goreta et al, 2012 ; Öncül et al, 2022 ). Dysmorphic features usually described in those patients are inverted, wide-set nipples, abnormal fat pads, orange peel skin, high forehead, large ears, or thin upper lip ( Verheijen et al, 2020 ).…”

Glycosylation and behavioral symptoms in neurological disorders

“…In addition, DPAGT1 homozygous knockout mouse models were found to be embryonic lethal. Other N-glycosylation-related CDGs include ALG1-CDG, which results in intellectual disability, developmental delay, and epilepsy [ 49 ]; NGLY1-CDG, which causes intellectual disability and alacrimia [ 34 ]; and SRD5A3-CDG, which causes severe developmental disability, skin problems, cerebellar ataxia and ocular anomalies [ 34 , 50 ]. The CDGs listed here are CDGs that display phenotypic features associated with neurological disorders.…”

Normal transferrin glycosylation does not rule out severe ALG1 deficiency

“…ALG1‐CDG (Online Mendelian Inheritance in Man [OMIM] #608540) is one of the most common CDG 17 . Since its discovery in 2004 18–20 more than 40 gene variants have been described 21 …”

“…17 Since its discovery in 2004 [18][19][20] more than 40 gene variants have been described. 21 Most patients suffer from neurological involvement: hypotonia, intellectual disability, seizures and microcephaly. There is often cerebral/cerebellar atrophy.…”