Journal of Inherited Metabolic Disease

, Volume 32, Supplement 1, pp 259–264

A new case of ALG8 deficiency (CDG Ih)

  • K. Vesela
  • T. Honzik
  • H. Hansikova
  • M. A. Haeuptle
  • J. Semberova
  • Z. Stranak
  • T. Hennet
  • J. Zeman
SHORT REPORT

DOI: 10.1007/s10545-009-1203-z

Cite this article as:
Vesela, K., Honzik, T., Hansikova, H. et al. J Inherit Metab Dis (2009) 32(Suppl 1): 259. doi:10.1007/s10545-009-1203-z

Summary

Congenital disorders of glycosylation (CDG) represent an expanding group of inherited diseases. One of them, ALG8 deficiency (CDG Ih), leads to protein N-glycosylation defects caused by malfunction of glucosyltransferase 2 (Dol-P-Glc:Glc1-Man9-GlcNAc2-P-P-Dol glucosyltransferase) resulting in inefficient addition of the second glucose residue onto lipid-linked oligosaccharides. So far, only five patients have been described with ALG8 deficiency. We present a new patient with neonatal onset. The girl was born at the 29th week of gestation complicated by oligohydramnios. Although the early postnatal adaptation was uneventful (Apgar score 8 and 9 at 5 and 10 min), generalized oedema, multifocal myoclonic seizures, and bleeding due to combined coagulopathy were present from the first day. Diarrhoea progressing to protein-losing enteropathy with ascites and pericardial effusion developed in the third week of life. Pharmacoresistant seizures and cortical, cerebellar and optic nerve atrophy indicated neurological involvement. No symptoms of liver disease except coagulopathy were observed; however, steatofibrosis with cholestasis was found at autopsy. The girl died at the age of 2 months owing to the progressive general oedema, bleeding and cardio-respiratory insufficiency. Molecular analysis revealed two heterozygous mutations in the ALG8 gene: c.139A>C (p.T47P) and the novel mutation c.1090C>T (p.R364X). Conclusion: The prognosis of patients with ALG8 deficiency is unfavourable. The majority of affected children have early onset of the disease with heterogeneous symptoms including multiple organ dysfunction, coagulopathy and protein-losing enteropathy. Neurological impairment is not a general clinical symptom, but it has to be taken into consideration when thinking about ALG8 deficiency.

Abbreviations

CDG

congenital disorder of glycosylation

CDT

carbohydrate-deficient transferrin

Dol

dolichol

IEF

isoelectric focusing

LLO

lipid-linked oligosaccharide

NLO

protein N-linked oligosaccharide

PLE

protein-losing enteropathy

PMI

phosphomannose isomerase

PMM

phosphomannomutase

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • K. Vesela
    • 1
  • T. Honzik
    • 1
  • H. Hansikova
    • 1
  • M. A. Haeuptle
    • 2
  • J. Semberova
    • 3
  • Z. Stranak
    • 3
  • T. Hennet
    • 2
  • J. Zeman
    • 1
  1. 1.Department of Pediatrics, First Faculty of MedicineCharles UniversityPrague 2Czech Republic
  2. 2.Institute of PhysiologyUniversity of ZürichZürichSwitzerland
  3. 3.Institute for the Care of Mother and ChildPragueCzech Republic