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Objective: To study the molecular genetic mechanism and genetic diagnosis of pyruvate dehydrogenase complex deficiency (PHD), and to provide a basis for genetic counseling and prenatal genetic diagnosis of PHD., Methods: Polymerase chain reaction (PCR) was performed to amplify the 11 exons and exon junction of the PDHA1 gene from a child who was diagnosed with PHD based on clinical characteristics and laboratory examination results. The PCR products were sequenced to determine the mutation. An analysis of amino acid conservation and prediction of protein secondary and tertiary structure were performed using bioinformatic approaches to identify the pathogenicity of the novel mutation., Results: One novel duplication mutation, c.1111_1158dup48bp, was found in the exon 11 of the PDHA1 gene of the patient. No c.1111_1158dup48bp mutation was detected in the sequencing results from 50 normal controls. The results of protein secondary and tertiary structure prediction showed that the novel mutation c.1111 _1158dup48bp led to the duplication of 16 amino acids residues, serine371 to phenylalanine386, which induced a substantial change in protein secondary and tertiary structure. The conformational change was not detected in the normal controls., Conclusions: The novel duplication mutation c.1111_1158dup48bp in the PDHA1 gene is not due to gene polymorphisms but a possible novel pathogenic mutation for PHD.

Objective: Glycogen storage disease type Ib (GSDIb) is caused by a deficiency of glucose-6-phosphate translocase (G6PT) activity due to SLC37A4 gene mutations. Most GSDIb patients have recurrent infections and inflammatory bowel disease, with poor prognosis. Detection of SLC37A4 gene mutations is of great significance for the diagnosis, subtyping and outcome prediction of GSD patients. This study aims to analyze SLC37A4 gene mutations in Chinese GSDIb patients and to investigate the relationship between its genotypes and clinical manifestations., Methods: All exons and their flanking introns of SLC37A4 gene in 28 Chinese children with a primary diagnosis of GSDIb were screened by PCR combined with direct DNA sequencing to detect SLC37A4 gene mutations., Results: Five SLC37A4 gene mutations were detected in 7 (25%) of the 28 children, i.e., p.Gly149Glu (9/13, 69%), p.Gly115Arg (1/13, 8%), p.Pro191Leu (1/13, 8%), c.959-960 insT (1/13, 8%) and c.870+5G>A (1/13, 8%)., Conclusions: In this study, c.959-960 insT is a novel mutation and p.Gly149Glu is the most common mutation. p.Gly149Glu may be associated with severe infections in children with GSDIb.

Glycerol kinase deficiency (GKD), a rare X-linked recessive disorder, is classified into two types: isolated and complex. Complex GKD is an Xp21 contiguous gene deletion involving the glycerol kinase locus together with the adrenal hypoplasia congenita (AHC) or Duchenne muscular dystrophy (DMD) loci or both. Its clinical features depend on the involved loci. GKD can be confirmed by an elevated urinary glycerol concentration tested by gas chromatography mass spectrometry (GC/MS). The three cases reported here were all male, presenting symptoms from neonatal period. The predominant clinical profile was characterized by hypoadrenocorticism, glyceroluria and Duchenne muscular dystrophy. After receiving a low fat diet and glucocorticoid replacement, they improved with relieved symptoms of hypoadrenocorticism. But they had significant developmental delays and myasthenia. In the follow-up two of them died of adrenal crisis.