Arylsulfatase A deficiency (metachromatic leukodystrophy; MLD) | ARSA | AR | All MLD features can be found in MSD, incl central & peripheral demyelination & progressive neurologic deterioration | Absence of other systemic findings assoc w/MSD |
Saposin B deficiency (OMIM 249900) | PSAP | AR | All saposin B deficiency features can be found in MSD, incl central & peripheral demyelination & progressive neurologic deterioration | Absence of other systemic findings assoc w/MSD |
Mucolipidosis II (I-cell disease) | GNPTAB | AR | Severe infantile onset, progressive neurologic deterioration, skeletal deformities (incl dysostosis multiplex), postnatal growth restriction, cardiac involvement, skin thickening, recurrent ear infections | Severe contractures (although joint mobility issues may be seen in MSD) |
Krabbe disease | GALC | AR | Central & peripheral demyelination, progressive neurologic deterioration | Absence of: cardiac & ophthalmologic complications, skeletal involvement (incl dysostosis multiplex), ichthyosis, hydrocephalus, hepatosplenomegaly, oral & dental issues, hearing loss, recurrent ear infections, upper airway obstruction |
Alexander disease | GFAP | AD | Central demyelination & hydrocephalus, progressive neurologic deterioration | Absence of: cardiac & ophthalmologic complications, skeletal involvement (incl dysostosis multiplex), ichthyosis, hepatosplenomegaly, oral & dental issues, hearing loss, recurrent ear infections, upper airway obstruction |
Canavan disease | ASPA | AR | Central demyelination, progressive neurologic deterioration, macrocephaly | Absence of: cardiac & ophthalmologic complications, skeletal involvement (incl dysotosis multiplex), ichthyosis, hepatosplenomegaly, oral & dental issues, hearing loss, recurrent ear infections, upper airway obstruction |
Fucosidosis (OMIM 230000) | FUCA1 | AR | Progressive neurologic deterioration, dysostosis multiplex, coarse facial features | Absence of: cardiac & ophthalmologic complications, ichthyosis, hepatosplenomegaly, oral & dental issues, hearing loss, recurrent ear infections, upper airway obstruction |
MPS I 1 | IDUA | AR | DD, skeletal involvement, growth restriction, corneal clouding, cardiac involvement, hepatosplenomegaly, dysmorphic features | Facial dysmorphic features & cardiac involvement are more prominent in MPS I. |
MPS II (Hunter syndrome) | IDS | XL | DD, short stature, skeletal involvement, hepatosplenomegaly, dysmorphic features | Affected females are rare. Corneal clouding is not a typical feature. |
MPS III (Sanfilippo syndrome) (OMIM 252900, 252920, 252930, 252940) | GNS HGSNAT NAGLU SGSH | AR | Neurodegeneration, DD, hepatosplenomegaly (<50% of individuals w/Sanfilippo syndrome) | May have slower, more insidious course presenting mainly w/cognitive & neurologic signs & symptoms |
MPS IV (Morquio syndrome) (see MPS IVA, GLB1-Related Disorders) | GALNS GLB1 | AR | Skeletal involvement, hearing loss, facial dysmorphic features | More severe skeletal involvement; MPS IVA does not present w/ID. |
MPS VI (Maroteaux-Lamy syndrome) (OMIM 253200) | ARSB | AR | Dysmorphic features, hepatosplenomegaly, short stature, corneal clouding, skeletal involvement | More severe skeletal involvement; Absence of ID |
X-linked ichthyosis (OMIM 308100) | STS | XL | Corneal opacities, ichthyosis | Affected females are rare. Absence of DD & neurodegeneration |
Chondrodysplasia punctata 1, X-linked | ARSL (ARSE) | XLR | DD in 15%-20% of affected individuals, short stature, epiphyseal stippling, cataracts, hearing loss | Affected females are rare. Characteristic facial appearance; Absence of neurodegeneration |
Hexosaminidase A deficiency (Tay-Sachs disease) | HEXA | AR | Progressive neurodegeneration, DD, spasticity, blindness, death in infancy | Cherry red spot of the fovea 2; Absence of skeletal abnormalities & hepatomegaly |
Hexosaminidase A/B deficiency (Sandhoff disease) (OMIM 268800) | HEXB | AR | Progressive neurodegeneration, DD, spasticity, blindness, death in infancy | Cherry red spot & ↑ startle response 3; hepatomegaly & skeletal abnormalities are less common than in MSD |