A new mutation was identified in a baby girl with congenital neuronal ceroid lipofuscinosis (CLN10), a rare disease that belongs to the heterogeneous group of neuronal ceroid lipofuscinoses (NCL), also known as Batten disease.
The study, “Congenital Neuronal Ceroid Lipofuscinosis with a Novel CTSD Gene Mutation: A Rare Cause of Neonatal-Onset Neurodegenerative Disorder,” was published in the journal Neuropediatrics.
Although the classification of the different types of NCLs has been based on the age of onset of the first clinical symptoms, new techniques are coming into use that facilitate disease diagnosis. To date, 13 genetic mutations have been associated with different forms of NCL.
CLN10 represents the earliest and most severe form of Batten disease, and is caused by a mutation in the gene encoding for cathepsin D (CTSD). The condition is usually associated with congenital microcephaly, brain atrophy, respiratory insufficiency, neonatal seizures, and other clinical symptoms during the first days or weeks of life.
The infant was the second child of consanguineous, first-cousin parents of Somalian origin. The pregnancy was uneventful and routine prenatal ultra-sound scans were all within the normal range.
She showed poor spontaneous breathing and was incubated. She also did not preform many spontaneous movements due to low muscle tone in the arms and limbs, and had convulsions four hours after her birth.
At age 3 days, a standard brain magnetic resonance imaging (MRI) was performed. Results revealed severe brain deformations in multiple areas, including dramatic cerebral and cerebellar shrinking. A molecular analysis of 225 genes associated with prenatal or perinatal onset of neurodegenerative diseases, called whole exome sequencing (WES), was also preformed. It indicated the presence of a genetic mutation that was not previously reported in the literature — a deletion of part of the CTSD gene.
Further functional studies, based on the absence of cathepsin-D protein in skin cells, confirmed the diagnosis of CLN10.
Both parents were heterozygous carriers of the same gene variant — meaning each carried one defective copy of the gene.
“It is important to emphasize that the presence of such dramatic early onset cerebral and cerebellar shrinking in a neonate should alert the clinician and prompt consideration of CLN10, particularly in the context of consanguineous parents,” the researchers concluded.