Clinical investigation of monozygotic twins with glutaric acidemia type I and gene mutation analysis

Abstract

Objective To review the clinical features of a Chinese family with glutaric acidemia type Ⅰ and analyze the glutaryl-CoA dehydrogenase(GCDH) gene mutation. Methods The patient's clinical data were collected from glutaric acidemia type Ⅰ family, including data of brain computer tomography (CT), magnetic resonance imaging (MRI) examination, urine organic acid and blood carnitine tandem mass analysis.The family members' genomic DNA was extracted from peripheral blood leukocytes.The 11 exons and their flanking sequences of GCDH gene were amplified with PCR and subjected to direct DNA sequencing. Results The proband's head circumference and visible exte-rior were normal.The Glasgow Coma Scale(GCS) score of the patient was 15.The four limbs activities and muscular tension were normal.The muscle strength was grade V. The Babinski sign, Brinell syndrome and Klinefelter syndrome were negative.CT findings revealed widened bilateral frontotemporal subdural interval, mild hydrocephalus, equidensite arc shadow at the right frontal parietal.MRI findings demonstrated bilateral frontotemporal atrophy, broadened cerebral sulci, fissures, sylvian fissure and subarachnoid space in the front temporal lobe.The T1, T2 and diffusion weighted image showed abnormal signals in the bilateral globus pallidus and the central white matter of the frontal lobe.The density of cerebral hemisphere white matte was attenuated.In the temporal parietal subdural, equal T1, moderate T2 and high intensity fluid-attenuated inversion recovery signals were detected.The inherited metabolic diseases screening showed high urinary glutaric acid excretion.The blood glutarylcarnitine was 0.34 μmol/L (0-0.20 μmol/L as normal reference) which was detected by tandem mass spectrometry.GCDH gene sequencing analysis confirmed that the proband was compound heterozygous mutations with c. 1205G>A and IVS10-2A>C.The pedigree analysis revealed that the proband's monozygotic twin little sister was also an glutaric acidemia type Ⅰ patient.The genotype of the little sister was completely consistent with proband.The clinical symptoms and disease severity were similar between the monozygotic twins. Conclusions The monozygotic twins who shared the same mutation and genetic background can have similar phenotypes and clinical symptoms.IVS10-2A>C is the prevalent GCHD gene mutation type in Chinese glutaric acidemia type I patients. Key words: Glutaric acidemia type Ⅰ; Glutaryl-CoA dehydrogenase; Monozygotic twins; Inborn errors metabolism; Compound heterozygous