Last modified: 2018-09-09
Abstract
Background: Leukodystrophy is a broad spectrum disorders that exhibit variable clinical symptoms and clinical course. Definite diagnosis may depend on genetic or metabolic studies. Whole exome sequencing now becomes more affordable and available in clinical practice.
Method: Total 30 cases of developmental delay and encephalopathy were enrolled for analysis using whole exome sequencing.
Result: Of those with whole exome sequencing, one patient (3.3%) was found to have GFAP c.1121A>G mutation, and was confirmed to have autosomal dominant Alexander disease. That is a 4-year-old girl with focal motor seizures and development delay since 6 months old. The brain magnetic resonance image revealed increased signal on T2WI near both caudate nuclei. There were hypomyelination near both frontal central parenchyma. Oral glucose lactate stimulation test was positive initially, suggesting mitochondrial disease. Although muscle pathology didn’t show ragged-red fibers, abnormal mitochondrion in muscle was found using electron microscopy. Electron transport chain activity of muscle also revealed low activity and the mtDNA copy number was 60%. She can walk without support for a short distance at one year old but still unsteady. She could grab things and held spoon by herself. The language development is only “MaMa”. She could follow simple instruction and make sounds to express her need under present treatment.
Conclusion: The whole exome sequencing is a powerful and promising diagnosis tool in clinical suspicious case of metabolic or genetic encephalopathy. Correct diagnosis may change the long-term outcome of the patient.