title: A new case of ALG8 deficiency (CDG Ih).
abstract: 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-Man(9)-GlcNAc(2)-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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, First Faculty of Medicine, Charles University, Ke Karlovu 2, 128 08, Prague 2, Czech Republic. kata.vesela@volny.cz
authors.forename: K
authors.initials: K
authors.lastname: Vesela
authors.forename: T
authors.initials: T
authors.lastname: Honzik
authors.forename: H
authors.initials: H
authors.lastname: Hansikova
authors.forename: M A
authors.initials: MA
authors.lastname: Haeuptle
authors.forename: J
authors.initials: J
authors.lastname: Semberova
authors.forename: Z
authors.initials: Z
authors.lastname: Stranak
authors.forename: T
authors.initials: T
authors.lastname: Hennet
authors.forename: J
authors.initials: J
authors.lastname: Zeman
mesh_terms: D019943:Amino Acid Substitution; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005234:Fatty Liver / Q000201:enzymology / Q000235:genetics; D005260:Female; D005964:Glucosyltransferases / Q000172:deficiency* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense
chemical_list: D050505:Mutant Proteins; C473777:ALG8 protein, human; D005964:Glucosyltransferases
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