Novel Mutations in NPC1 are Associated with Pelizaeus-Merzbacher-Like Disease: A Case Report

Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating leukodystrophy with clinical symptoms and imaging manifestations similar to those of Pelizaeus-Merzbacher disease (PMD), an X-linked recessive hypomyelinating leukodystrophy. Typical manifestations of PMLD are nystagmus, dysmyotonia, ataxia, progressive motor dysfunction, and diffuse leukodystrophy on magnetic resonance imaging (MRI). This report identified novel mutations in NCP1 causing PMLD. A 7-month-old male patient was referred to our hospital because he could not lift his head until that time. He had symptoms including congenital nystagmus, hypotonia, and developmental delay. According to the MRI scan, there were signs of leukodystrophy. According to the clinical manifestations and the results of whole-exome sequencing (compound heterozygote mutations in NPC1 (p. G911S, c2731G>A and p. D128H, c382G>C)), the diagnosis of PMLD was considered, and his parents were determined to be carriers of mutant genes. He began rehabilitation training at the age of 1 year old. After 5 years of training, he was still experiencing global developmental delay, equivalent to the developmental level of a nine-month-old child. PMLD is a disease that seriously affects the quality of life of children and can result from mutations in different genes. In this report, we expand the gene spectrum of PMLD and suggest early genetic counselling for suspected patients and their patients.