Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome

doi:10.1016/0009-8981(84)90059-7

Clinica Chimica Acta

Volume 144, Issues 2–3, 29 December 1984, Pages 245-247

https://doi.org/10.1016/0009-8981(84)90059-7 Get rights and content

Abstract

Identical twin-sisters with evidence of a demyelinating disease showed multiple serum glycoprotein abnormalities. The association of a low serum iron level and a normal blood haemoglobin suggested an abnormality of transferrin too. This was confirmed by finding a sialic acid-deficiency of this glycoprotein in serum as well as in cerebrospinal fluid.

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Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG-deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome?
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Citation Excerpt :
Regarding P3, the apoC-III profile was clearly abnormal, with markedly increased non-glycosylated apoC-III0 (10%), and with apoC-III2 and apoC-III1 in normal proportions, corresponding to a typical COG-CDG “apoC-III0” 2-DE profile. Since the first description of PMM2-CDG by Jaeken et al. in 1984 [5], the advances in clinical biochemistry and genetics have led to a rapid expansion of the CDG family. More recently, a CDG subfamily characterized by Golgi homeostasis disruption and a type II Trf pattern has been identified, where mutations are found on genes coding for Golgi proton pump subunits [7], vesicular traffic proteins [6] and Mn2+ transporters [8], resulting in decreased glycosyltransferases catalytic activities and/or altered localizations.
We identified three cases of congenital disorders of glycosylation (CDG) with Golgi homeostasis disruption, one ATP6V0A2-CDG and two COG4-CDG, with normal transferrin screening analyses. Patient 1 (P1) presented at birth with cutis laxa. Patient 2 (P2) and patient 3 (P3) are adult siblings and presented with severe symptoms evocative of inborn errors of metabolism.
Targeted gene sequencing in P1 revealed pathogenic ATP6V0A2 variants, shared by her affected older brother. In P2 and P3, whole exome sequencing revealed a homozygous COG4 variant of unknown significance. In all affected individuals, transferrin analysis was normal.
Mass-spectrometry based serum N-glycome analysis and two-dimensional electrophoresis (2-DE) of haptoglobin and of mucin core 1 O-glycosylated apolipoprotein C-III (apoC-III) were performed. All results of second-line N-glycosylation analyses were initially normal. However, apoC-III 2-DE revealed characteristic “apoC-III₁” pattern in P1 and specific “apoC-III₀” patterns in P2 and P3. In P2 and P3, this allowed reclassifying the variant as likely pathogenic according to ACMG guidelines.
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Short communicationSialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome

Abstract

Clin Chim Acta

Int J Biochem

Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG-deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome?

Pediatr Res

Short communication
Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome