Three siblings with neuronal ceroid lipofuscinosis type 7 and 2 novel mutations in their MFSD8 gene

Objective The neuronal ceroid lipofuscinosis (CLN) are a group of severe lysosomal storage diseases.The patients present with clinically and genetically heterogeneous neurodegenerative disorders.This study aims to investigate the clinical characteristics and the gene mutations of a rare Chinese family with 3 siblings affected by CLN7. Methods The proband, a 5-year-old girl, visited us because of intermittently seizures and mental retardation for 2 years and a half in December, 2015.Clinical investigation, brain magnetic resonance imaging(MRI), biochemical and the gene analysis were performed for the etiological study. Results The proband had seizures at the age of 2 and a half years, with the progressive motor deterioration, speech disturbance, mental regression and vision loss.Her brain MRI showed diffusive cerebral atrophy.The blood aminoacids, acylcarnitine and urine organic acid profiles were normal.Lysosomal palmitoyl protein thioesterase and tripeptidyl peptidase activities of peripheral leukocytes were normal.A compound heterozygous mutation of c. 1351-1G>A and c. 300T>G was detected on her MFSD8 gene, supporting the diagnosis of CLN7.Both of the 2 mutations were novel.Each of her parents carried one of the mutations.Two brothers of the proband had similar clinical process.Her elder brother died at the age of 7 due to severe encephalopathy of unknown etiology.The younger brother showed dyskinesia from the age of 2 years and seizures from the age of 4 years.A compound heterozygous mutation on MFSD8 gene, c.1351-1G>A and c. 300T>G, was found from the younger brother, as same as the proband. Conclusions CLN7 is a rare disorder of CLN.In this study, the diagnosis of the 3 siblings with similar clinical process were much delayed.Gene analysis was key for the diagnosis.Two novel mutations were found on MFSD8 of the family.There is still no effective treatment for neurol ceroid lipofuscinosis.The prognosis is poor.Based on the mutation diagnosis, prenatal diagnosis for the next sibling is possible to the prevention of the disease. Key words: Neuronal ceroid lipofuscinosis; Neurodegenerative disorders; Lysosomal storage diseases; MFSD8 gene