Two novel mutations in the SLC37a4 gene in a child with glycogen storage disease type Ib
Introduction. Glycogen storage disease (GSD) type Ib is caused by mutations in the SLC 37A4 gene. The aim of the study. To verify the diagnosis by molecular genetic studies. Patient. Child at the age of 5 years and 8 months with severe hepatomegaly, nephromegaly, neutropenia, hypoglycemia, metabolic lactate acidosis, hyperlipidemia, cytolytic and cholestatic syndromes. Methods. The diagnosis was confirmed by means of the molecular genetic study. Genomic DNA was isolated from whole venous blood with the use of the phenol-chloroform extraction. Fragments of genes G6PC and SLC 37A4, containing all coding areas with adjacent intron regions isolated by polymerase chain reaction (PCR) with the use of specific primers. Then all the products were analyzed by automated sequencing by using of BigDye Terminator Cycle Sequencing Ready Reaction kit (Applied Biosystems, Foster City, CA, USA) on an automated DNA sequencer ABI 3500 XL (Applied Biosystems). Results. Mutations have been identified In exons 04 and 09 SLC 37A4 gene c.345dup (p.Leu116Alafs*15), and c.1077 1078insG (p.An360Glufs*42), respectively. Both mutations lead to premature termination of translation of the amino acid sequence of the encoded protein. Mutations not previously described in the HGMD database and in silico data analysis with the using a computer software Alamut Visual with built-in mutation tester (Interactive Biosoftware), both mutations are pathogenic. The patient was prescribed a specific diet with the exclusion of complex carbohydrates from the diet, the addition of uncooked cornstarch, as well as therapy with hepatoprotectors and granulocyte colony stimulating factor. Against background of following these recommendations there was noticed the positive dynamics in the patient's condition. Conclusion. Thus by direct automatic sequencing we have identified 2 novel mutations in the SLC 37A4 gene, which allowed to confirm the diagnosis of GSD Ib type in the child patient, timely to initiate adequate therapy and to achieve positive dynamics in the patient’s state of health.