The Spectrum of Inherited Gray Matter Degenerative Brain Disorders (DBD) in Children: A Single-Center Study

OBJECTIVES: To study the clinical spectrum of inherited gray matter degenerative brain disorders (DBD) in children. METHODS: This cross-sectional study evaluated children up to 12 y of age, diagnosed with an inherited gray matter DBD in a tertiary care pediatric hospital between July 2019 and December 2020. RESULTS: A total of 314 children with progressive neuroregression were screened. Of these, 117 children with inherited gray matter DBD were included in the study. The clinic-based prevalence of DBD was 8.2%, and inherited gray matter DBD was 3.1%. The proportion of the inherited gray matter DBD was 37.3% among the overall DBD cases. Children were categorized into three groups based on the age at onset of disease: below 2 years (N = 57, 48.7%), between 2 and 5 years (N = 32, 27.3%), and between 6 and 12 years (N = 28, 23.9%). Based on the predominant cerebral structure involved, gray matter DBD were classified as cerebral gray matter disorders (53%), basal ganglia disorders (34.1%), and cerebellar disorders (12.8%). Overall, the most common disorders were Wilson disease (18%), neuronal ceroid lipofuscinosis (NCL) (17%), and neurodegeneration with brain iron accumulation (NBIA) (16%). The most common gray matter DBD in children <2 years of age were NBIA (n = 11), Rett syndrome (n = 11), and gangliosidoses (n = 10). NCL (n = 14) and ataxia telangiectasia (n = 6) were most common in the age group of 2–5 years. Wilson disease (n = 19) was the most common disorder in the age group of 6–12 years followed by NCL (n = 4) and NBIA (n = 3). CONCLUSION: Our study highlights the burden and spectrum of gray matter DBD in children. The clinic-based prevalence of DBD was 8.2%, and of inherited gray matter DBD was 3.1%. The proportion of inherited gray matter DBD was 37.3% among the overall DBD cases. Wilson disease, NCL, and NBIA are the most common gray matter DBD in children. Timely diagnosis is important for the prevention of recurrence in subsequent pregnancies.