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Orphanet J Rare Dis. 2015 Jun 12;10:73. doi: 10.1186/s13023-015-0289-7.

ALG8-CDG: novel patients and review of the literature.

Author information

1
Medical University of Innsbruck, Clinic for Pediatrics II, Division of Neonatology, Innsbruck, Austria. Michaela.hoeck@i-med.ac.at.
2
Medical University of Innsbruck, Clinic for Pediatrics II, Division of Neonatology, Innsbruck, Austria. karina.wegleiter@i-med.ac.at.
3
Medical University of Innsbruck, Clinic for Pediatrics II, Division of Neonatology, Innsbruck, Austria. Elisabeth.ralser@i-med.ac.at.
4
Medical University of Innsbruck, Clinic for Pediatrics II, Division of Neonatology, Innsbruck, Austria. Ursula.kohlendorfer@i-med.ac.at.
5
Medical University of Innsbruck, Clinic for Pediatrics I, Inherited Metabolic Disorders, Anichstrasse 35, 6020, Innsbruck, Austria. sabine.scholl-buergi@uki.at.
6
Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria. Christine.fauth@i-med.ac.at.
7
Medical University of Innsbruck, Clinic for Pediatrics I, Inherited Metabolic Disorders, Anichstrasse 35, 6020, Innsbruck, Austria. Elisabeth.steichen@i-med.ac.at.
8
Medical University of Innsbruck, Clinic for Pediatrics I, Inherited Metabolic Disorders, Anichstrasse 35, 6020, Innsbruck, Austria. ka.pichler@uki.at.
9
Department of Neurology, Translational Metabolic Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Medical Center, Nijmegen, The Netherlands. Dirk.Lefeber@radboudumc.nl.
10
Center for Human Genetics of the University of Leuven, Leuven, Belgium. gert.matthijs@uzleuven.be.
11
Center for Human Genetics of the University of Leuven, Leuven, Belgium. Liesbeth.Keldermans@med.kuleuven.be.
12
Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria. kathrin.maurer@i-med.ac.at.
13
Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria. Johannes.zschocke@i-med.ac.at.
14
Medical University of Innsbruck, Clinic for Pediatrics I, Inherited Metabolic Disorders, Anichstrasse 35, 6020, Innsbruck, Austria. daniela.karall@i-med.ac.at.

Abstract

BACKGROUND:

Since 1980, about 100 types of congenital disorders of glycosylation (CDG) have been reported representing an expanding group of inherited disorders. ALG8-CDG (= CDG-Ih) is one of the less frequently reported types of CDG, maybe due to its severe multi-organ involvement with coagulation disturbances, edema, massive gastrointestinal protein loosing enteropathy, cataracts, and often early death. We report three additional patients, provide an update on two previously reported, and summarize features of ten patients reported in literature.

RESULTS:

Of 15 ALG8-CDG patients, three were homozygous and 12 compound heterozygous. There were multiple prenatal abnormalities in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13.

CONCLUSION:

In ALG8-CDG, isoelectric focusing of transferrin in serum or plasma shows an abnormal sialotransferrin pattern. The diagnosis is confirmed by mutation analysis in ALG8; all patients reported so far had point mutations or small deletions. The prognosis is generally poor. Thus, a timely and correct diagnosis is important for counselling.

PMID:
26066342
PMCID:
PMC4504351
DOI:
10.1186/s13023-015-0289-7
[Indexed for MEDLINE]
Free PMC Article

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