Abstract:

Objective To summarize the clinical characteristics in children harboring GFM1 gene mutations. Methods Retrospective analysis about the clinical features was performed in a patient with biallelic GFM1 mutations. Mitochondrial translation factor G1 (mtEFG1) space structure was constructed to verify the hypothesis about the relation between GFM1 gene missense mutations and the results of clinical phenotypes. Results The patient was a girl aged six months and twenty-eight days. Growth retardation, abnormal liver function, jaundice, hepatomegaly and splenomegaly were presented with in poor response and lethargy. Serum biochemical tests demonstrated elevation in total bilirubin, direct bilirubin, aspartate transaminase, alkaline phosphatase, gamma-glutamyltransferase, blood ammonia and blood lactic acid, as well as hypoalbumineamia, prolonged PT, acidosis, and hypoglycemia.Mass spectrometry of serum amino acids & acyl carnitine and urine urine organic acids suggested elevation of many amino acids in serum and ketonuria. Abnormal signals were observed in bilateral thalamus, cerebral peduncle, basal ganglia, and medial anterior occipital lobes through cranial MRI. Sequencing of GFM1 revealed compound heterozygous mutations: a missense mutation c.688G>A (p.Gly230Ser) in exon 5 and a frameshift deletion c.1686delG (p.Asp563Thrfs*24) in exon 14. Gly230Ser protein changed amino acid residue in the structure of peripheral mtEFG1 space, changes in which area resulted in encephalopathy. Conclusion A Chinese girl carrying compound heterozygous GFM1 gene mutations of c.688G>A and c.1686delG was reported. Hepatic presentation of this case denied the assumption that missense mutations in GFM1 gene that changes the peripheral amino acids of the protein will cause phenotype of encephalopathy.