Congenital disorder of glycosylation type Ig (ALG12‐CDG) is a rare inherited metabolic disease caused by a defect in alpha‐mannosyltransferase 8, encoded by the ALG12 gene (22q13.33). To date, only 15 patients have been diagnosed with ALG12‐CDG globally. Due to a newborn Slovak patient's clinical and biochemical abnormalities, the isoelectric focusing of transferrin was performed with observed significant hypoglycosylation typical of CDG I. Furthermore, analysis of neutral serum N‐glycans by mass spectrometry revealed the accumulation of GlcNAc2Man5–7 and decreased levels of GlcNAc2Man8–9, which indicated impaired ALG12 enzymatic activity. Genetic analysis of the coding regions of the ALG12 gene of the patient revealed a novel homozygous substitution mutation c.1439T>C p.(Leu480Pro) within Exon 10. Furthermore, both of the patient's parents and his twin sister were asymptomatic heterozygous carriers of the variant. This comprehensive genomic and glycomic approach led to the confirmation of the ALG12 pathogenic variant responsible for the clinical manifestation of the disorder in the patient described.
AIM: Congenital disorders of glycosylation (CDG) belong to an expanding group of rare genetic metabolic disorders caused by defects in the complex chemical enzymatic process of glycosylation. The study is aimed at presenting a case report of a premature dysmorphic newborn, clinical presentation of the condition, the way it was diagnosed and treated, as well as its comparison with the known cases. RESULTS: The result of glycan analysis supports the assumption of a supposed glycosylation disorder and also specifi es a specifi c subtype: CDG-1, subtype ALG12-CDG (Ig). CONCLUSION: CDG have an extremely wide clinical spectrum and should be considered in any child with unexplained developmental delay, failure to thrive, seizures, and abnormalities in liver enzymes, coagulation and immunologic factors. The treatment of most forms of CDG depends upon numerous factors such as specifi c symptoms present, severity of the disorder, age and overall health of the patients and tolerance to certain medications or procedures. For these reasons, the treatment is specifi c for every individual. It is based on the symptoms and requires a coordination of efforts of a team of specialists (Tab. 4, Fig. 3, Ref. 19).
Inherited metabolic disorders of glycoconjugate metabolism include congenital disorders of glycosylation (CDG)-disorders in biosynthesis of glycoconjugates; and some of the lysosomal storage diseases (LSD)-disorders of their degradation. This review summarizes the brief characteristics of metabolic pathways of synthesis and catabolism of glycoconjugates as well as the latest update of relevant enzymatic defects discovered in population. Every year the number of known subtypes of these disorders dramatically increases as a result of high-throughput analytical infrastructure applied. However, due to the broad spectrum of unspecifi c clinical symptoms, many patients remain undiagnosed or have wrong diagnosis with ineffective treatment. Thus, disorders of glycoconjugate metabolism should be considered and ruled out in any unexplained syndrome. The collaboration between scientists and physicians plays an important role in the progress of such personalized diagnostics, that is essential mainly for rare diseases (Tab. 2, Fig. 1, Ref. 49).
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