it is caused by a deficiency of both hexosaminidase ( hex ) a and b , resulting in accumulation of glycosphingolipids and oligosaccharides in the brain .
it has three clinical subtypes ( infantile , juvenile , and adult forms ) and represents around 7% of cases among all the lysosomal storage disorders .
the infantile form presents in the first 618 months of age with regression of milestones , developmental delay , startle response , hypotonia , cherry red spots , and convulsions .
we report this case as the infant presented with regression without hepatosplenomegaly and confirmed by gene testing .
a 1-year - old second born male child , born to a third - degree consanguineously married couple with uneventful perinatal history , was brought with regression of milestones and seizures . the onset of clinical symptoms began at the age of 6 months with gradual loss of the milestones .
the child had achieved response to sounds by 2 months ; head holding , social smile , and recognition of mother by 3 months of age .
initially , he lost social smile and recognition of mother followed by control of neck .
he lost all the milestones by 89 months of age . the child developed exacerbated startle response since 8 months of age and multiple episodes of right - sided focal seizures from 11 months of age .
there was a history of sibling death at the age of 18 months with similar complaints . on examination ,
head circumference was 44 cm ( between 3 and 15 centile ) with coarse facies .
the tone was increased in all the limbs with power of 3/5 ( medical research council grade ) .
fundus examination showed cherry - red spot in the macula , and there was no hepatosplenomegaly .
magnetic resonance imaging ( mri ) shows hyperintensity of the basal ganglia ( long white arrow ) and hypointensity of the ventral thalami ( open arrow ) on t2-weighted sequences [ figure 1 ] .
based on above findings suspected to be a case of sandhoff disease , the enzyme assay in leukocytes for  hexosaminidase total ( a + b ) revealed 61 nmhol / h / mg ( normal , 9052878 ) .
gene testing was positive for homogenous missense substitution p. cys534tyr , c1601g > a , chr5:74016560g > a in exon 13 of hexb gene .
axial t2-weighted imaging showing hyperintensity of the basal ganglia ( long white arrow ) and hypointensity of the ventral thalami ( open arrow )
our patient had presented with regression of milestones , exaggerated startle response , decreased vision , and seizures .
the child had coarse facies , cherry red spot , and normocephaly without hepatosplenomegaly . in a study conducted among 18 gm2 gangliosidosis patients by karimzadeh et al .
, seven patients had macrocephaly , three patients had microcephaly , and eight patients had a normal head circumference . a distinguishing feature in standoff 's disease from other gm2 gangliosidosis is presence of hepatosplenomegaly and n - acetylglucosamine - containing oligosaccharides in urine
likewise , karimzadeh et al . also noted , and only two patients of sandhoff disease out of their nine cases had hepatosplenomegaly .
similar observation was made by ozkara et al . in their study of 18 cases affected by sandhoff disease , and hepatosplenomegaly
was not found in 11 out of 18 infantile sandhoff disease patients , while the remaining seven had mild hepatosplenomegaly .
closest differential diagnosis of sandhoff disease is tay  sachs disease , which is characterized by the absence of coarse facies , hepatosplenomegaly , skeletal deformities , and signs of peripheral nerve involvement .
axial t2-weighted imaging on mri in our patient revealed hyperintensity of the basal ganglia and hypointensity of the ventral thalami .
also reported as bilateral thalamic hyperdensity on computed tomography and hypointensity on t2-weighted mri images as the earliest diagnostic markers of sandhoff disease .
the gold standard method for diagnosis of gm2 gangliosidosis is the measurement of -hex activity in plasma , serum , and/or fibroblasts .
molecular characterization of the hexa and hexb mutations can also be performed for confirmation by direct sequencing of the entire coding region and intron / exon boundaries using genomic dna .
the same mutation was reported previously in a japanese case which showed hepatosplenomegaly unlike our case . prenatal diagnosis advised for next pregnancy .
sachs disease if any child presenting with regression of milestones and cherry red spot without hepatosplenomegaly .
 sandhoff disease is a neurodegenerative disease caused due to deficiency of hexosaminidase ( hex ) a and b. a 1-year - old male child presented with regression of milestones , exaggerated startle response , decreased vision , and seizures from 6 months of age . 
 the child had coarse facies without hepatosplenomegaly . 
 serum levels of  hexosaminidase total ( a + b ) were low . 
 genetic testing for sandhoff disease revealed a homozygous missense variant on hexb gene . 
 the case is presented to highlight that the absence of hepatosplenomegaly should not restrain in suspecting sandhoff disease . 
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