Need et al. (2012) and Shashi (2013) reported a boy with a phenotype consistent with a congenital disorder of glycosylation. He presented with developmental delay, hypotonia, involuntary movements, intractable multifocal epilepsy, abnormal liver function, congenital absence of tears, ... Need et al. (2012) and Shashi (2013) reported a boy with a phenotype consistent with a congenital disorder of glycosylation. He presented with developmental delay, hypotonia, involuntary movements, intractable multifocal epilepsy, abnormal liver function, congenital absence of tears, peripheral neuropathy, and small hands and feet. At age 15 months he showed regression of motor development. At age 5 years he was able to sit up, reach for objects, transfer them from hand to hand, but never developed speech. Liver biopsy showed evidence of inflammatory changes with an amorphous substance in the cytoplasm. Urine oligosaccharides were abnormal, showing keratan sulfate, heparan sulfate, and chondroitin sulfate. Brain MRI showed prominent perivascular spaces with surrounding gliosis in periatrial white matter and mildly delayed myelination. Testing for congenital disorders of glycosylation had been normal by transferrin isoelectric focusing and N-glycan analysis.
By whole-exome sequencing in a family in which a boy had developmental delay, multifocal epilepsy, involuntary movements, abnormal liver function, and absent tears, Need et al. (2012) found that the boy was compound heterozygous for 2 mutations in ... By whole-exome sequencing in a family in which a boy had developmental delay, multifocal epilepsy, involuntary movements, abnormal liver function, and absent tears, Need et al. (2012) found that the boy was compound heterozygous for 2 mutations in the NGLY1 gene: a frameshift mutation in exon 12 (610661.0001) inherited from his mother, and a nonsense mutation in exon 8 (610661.0002) inherited from his father. Need et al. (2012) compared NGLY1 protein expression in leukocytes extracted from blood from the patient, his parents, and 3 controls. Both parents showed reduced expression compared with controls, and the patient had barely discernible levels of NGLY1.