OBJECTIVE: To explore the genetic basis for a girl featuring epilepsy, developmental delay and regression. METHODS: Clinical data of the patient was collected. Activities of hexosaminidase A (Hex A) and hexosaminidase A&B (Hex A&B) in blood leukocytes were determined by using a fluorometric assay. Peripheral blood samples were collected from the proband and six members from her pedigree. Following extraction of genomic DNA, whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Enzymatic studies of the proband have shown reduced plasma Hex A and Hex A&B activities. Genetic testing revealed that she has carried c.1260_1263del and c.1601G>C heterozygous compound variants of the HEXB gene. Her mother, brother and sister were heterozygous carriers of c.1260_1263del, while her father, mother, three brothers and sister did not carry the c.1601G>C variant, suggesting that it has a de novo origin. Increased eosinophils were discovered upon cytological examination of peripheral blood and bone marrow samples. CONCLUSION The compound heterozygous variants of c.1260_1263del and c.1601G>C of the HEXB gene probably underlay the Sandhoff disease in this child. Eosinophilia may be noted in infantile Sandhoff disease.
Child ; Eosinophilia/genetics* ; Female ; Genetic Testing ; Hexosaminidase A/genetics* ; Hexosaminidase B/genetics* ; Humans ; Male ; Mutation ; Pedigree ; Sandhoff Disease/genetics*

<b>OBJECTIVEb>To explore the clinical features and molecular mutation of HEXB gene in a case with juvenile Sandhoff disease.

<b>METHODb>We retrospectively reviewed the clinical, neuroimaging and biochemical findings in this Chinese child with juvenile Sandhoff disease. Hexosaminidase A and hexosaminidase A & B activities were measured in blood leukocytes by fluorometric assay. HEXB gene molecular analysis was performed by PCR and direct sequencing.

<b>RESULTb>The 9-year-old boy was admitted for psychomotor regression. He presented slowly progressive gait disorder and dysarthria during the last three years. Cranial MRI revealed a marked cerebellar atrophy with normal intensity in the thalamus and basal ganglia. Brain MRS showed normal in the thalamus and basal ganglia. Hexosaminidase A was 69.5 (mg·h) [normal controls 150-360 nmol/(mg·h)], hexosaminidase A & B activity was 119 nmol/(mg·h)[normal controls 600-3 500 nmol/(mg·h)], confirming the diagnosis of Sandhoff disease. The patient was a compound heterozygote for a novel deletion mutation c.1404delT (p. P468P fsX62) and a reported mutation c.1509-26G>A.

<b>CONCLUSIONb>The clinical features of juvenile Sandhoff disease include ataxia, dysarthria and cerebellar atrophy. The enzyme assay and molecular analysis of HEXB gene can confirm the diagnosis of Sandhoff disease. The novel mutation c.1404delT(p. P468P fsX62) is a disease-related mutation.

Brain ; diagnostic imaging ; pathology ; Cerebellar Ataxia ; diagnosis ; enzymology ; genetics ; Child ; DNA Mutational Analysis ; Heterozygote ; Hexosaminidase A ; blood ; metabolism ; Hexosaminidase B ; blood ; metabolism ; Humans ; Leukocytes ; enzymology ; Magnetic Resonance Imaging ; Male ; Mutation ; Radiography ; Retrospective Studies ; Sandhoff Disease ; diagnosis ; enzymology ; genetics ; beta-Hexosaminidase beta Chain ; genetics