Congenital disorders of glycosylation - an umbrella term for rapidly expanding group of rare genetic metabolic disorders - importance of physical investigation.

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 specifies a specific 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 specific 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 specific 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.

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 unspecific 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). Keywords: congenital disorders of glycosylation, lysosomal storage disorders.

Serum free carnitine in medium chain acyl-CoA dehydrogenase deficiency.

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder of fatty acid beta-oxidation and presents acutely with hypoglycemia, or a Reye-like illness with low free carnitine, often provoked by an infection or an excessive period of fasting. After acute attack these children are for the most time asymptomatic and may have normal plasma free carnitine concentrations. We observed a regularity in time course of serum free carnitine concentration during two attacks of Reye-like illness in patient with MCAD deficiency. Molecular investigation confirmed that the patient was homozygote for A985G mutation. Free carnitine was measured by enzymatic UV-test. First attack of severe hypoglycemia and Reye-like symptoms started at the age of 15 months and the second at the age of 25 months. In both episodes, treatment with intravenous glucose was given immediately, but without carnitine supplementation. Between the attacks patient was on a normal diet. In both attacks, low serum free carnitine concentration from the time of acute attack continually decreased for up to 8-13 days and then normalized at about 25 days after attack. We think that the time course of serum free carnitine may help in knowledge about carnitine depletion in MCAD deficiency. This is the first observation of this pattern during an acute attack and needs to be confirmed by other patients with MCAD deficiency. (Fig. 2, Ref. 7.).

Metabolic cause of Reye-like syndrome.

The most frequent metabolic cause of Reye-like syndrome is medium chain acyl-CoA dehydrogenase (MCAD) deficiency. The authors describe a gypsy boy who was repeatedly hospitalised due to symptoms of Reye-like syndrome (serious hypoglycemia, loss of consciousness, seizures, increased values of aminotransferases, decreased values of free carnitine). The diagnosis of MCAD deficiency was established by analysis of plasmatic acylcarnitines by use of tandem mass spectrometry. DNA analysis proved the most common K329E (G985) mutation in gene for MCAD deficiency in homozygous state. The authors have emphasised the advantage of tandem mass spectrometry in the diagnosis of disorders of fatty acid beta-oxidation. This highly sophisticated method can detect most of these disorders from dry blood spots disregarding the symptoms and type of mutation.