Figure 1
Features of Index Family. (A) Pedigree depicting family structure: Circle represent females, squares depict males. Consanguinity is shown via double lines linking parents. Affected status is denoted by a filled shape. Death is indicated by a slash. (B) Brain magnetic resonance imaging demonstrating generalized cortical atrophy in patient 3.
Figure 2
Clustal Omega cross-species alignment of amino acid residues. The proline at position 55 is conserved throughout eukaryotes.
Table 1
Clinical and genetic features of GM2A-associated disease
| Source | Mutation | Ethnicity | Age of Onset | Symptoms | Examination | Other |
|---|---|---|---|---|---|---|
| de Baecque, et al.12 | p.C107R homozygous | African American | 9 months | Decline in mobility; hyperacusis; regression | Hypotonia; increased DTRs; cherry red spots | Normal HexA and HexB activities; brain biopsy showed Zebra bodies and membranous cytoplasmic bodies; pleomorphic intracytoplasmic astrocytic inclusions; reported by Schroder et al.3 and Xie et al.4 |
| Schroder et al.13 | p.R169P homozygous | Indian | 5 months | Nystagmus, motor delay | Hyperacusis; juvenile spasms; cherry red spot | Normal HexA and HexB activities; rectal biopsy showed storage material; died at age 5 |
| Schepers et al.6 | p.H137fsX33 homozygous | Spanish | 7 months | Developmental delay | Hypotonia, limb hypertonia; hyperacusis; cherry red spots | Normal HexA and HexB activities; MRI showed ↑ cerebral and cerebellar white matter signal |
| Schepers et al.6 | p.88Ldel homozygous | Saudi | 8 months | Weakness; head lag; infantile spasms; tonic–clonic seizures | Hypotonia; ↓ visual attention; hyperacusis; cherry red spots | Normal HexA and HexB activities; diffuse brain atrophy on MRI; rapid progression after 24 months |
| Chen et al.7 | p.E54X homozygous | Laotian Hmong | 5 months | Developmental delay; weakness; extreme hyperacusis; generalized tonic–clonic and myoclonic seizures | Severe hypotonia; dysarthria, dysphagia; ↓ volitional movement; ↓ response to environment; roving eye movements; cherry red spots | Normal HexA enzyme activity; ↑ CSF gangliosides; abnormal basal ganglia and white matter signal |
| Present report (3 patients) | p.P55L homozygous | Saudi | 7 or 8 years | Anxiety, intellectual regression, chorea | Spastic quadriparesis, limb dystonia, pyramidal tract signs, chorea | Diffuse cortical atrophy |
[i] Hex A, Hexosaminidase A; Hex B, Hexosaminidase B; MRI, Magnetic Resonance Imaging.