Key characteristics of the three clinical forms of Gaucher disease
| Subtype . | Type I . | Type II . | Type III . | ||||
|---|---|---|---|---|---|---|---|
| Asymptomatic . | Symptomatic . | Neonatal . | Infantile . | IIIa . | IIIb . | IIIc . | |
| Common genotype | N370S/N370S or 2 mild mutations | N370S/other or 2 mild mutations | 2 null or recombinant mutations | 1 null and 1 severe mutations | None | L444P/L444P; 2 severe mutations | D409H/D409H |
| Ethnic predilection | Ashkenazi Jews | Ashkenazi Jews | None | None | None | Norbottnians; Asians; Arabs | Palestinian Arabs, Japanese |
| Common presenting features | None | Hepatosplenomegaly, hypersplenism, bleeding tendency, bone pains, growth retardation | Hydrops fetalis; ichthyosis | SNGP, strabismus opisthotonus, trismus | SNGP; myoclonic seizures; mild visceral involvement | SNGP; massive hepatosplenomegaly growth retardation | SNGP; cardiac valve calcifications; mild visceral involvement |
| Neurologic involvement | Early-onset parkinsonism or peripheral neuropathy (rarely) | Early-onset Parkinsonism or peripheral neuropathy (rarely) | Lethal | Severe | SNGP; slowly progressive neurologic deterioration | SNGP; gradual but progressive cognitive deterioration | SNGP; brachycephalus |
| Bone involvement | None | Mild to severe (variable) | None | None | Mild | Moderate to severe; kyphosis (gibbus) | Minimal in most; gibbus in the longest living |
| Lung involvement | None | None to (rarely) severe | Severe | Severe | Mild to moderate | Moderate to severe | Minimal |
| Life expectancy (if untreated) | Normal | Normal/near normal | Fetal/neonatal death | Death before 2 y | Death during childhood | Death in mid adulthood | Death in very early adulthood |
| Disease-specific treatment (2010) | None | ERT (or SRT if ERT unsuitable/not a therapeutic option) | None | Supportive (ERT not justified ethically) | ERT for visceral disease | ERT for visceral disease | Cardiac valve replacement if possible |
| Subtype . | Type I . | Type II . | Type III . | ||||
|---|---|---|---|---|---|---|---|
| Asymptomatic . | Symptomatic . | Neonatal . | Infantile . | IIIa . | IIIb . | IIIc . | |
| Common genotype | N370S/N370S or 2 mild mutations | N370S/other or 2 mild mutations | 2 null or recombinant mutations | 1 null and 1 severe mutations | None | L444P/L444P; 2 severe mutations | D409H/D409H |
| Ethnic predilection | Ashkenazi Jews | Ashkenazi Jews | None | None | None | Norbottnians; Asians; Arabs | Palestinian Arabs, Japanese |
| Common presenting features | None | Hepatosplenomegaly, hypersplenism, bleeding tendency, bone pains, growth retardation | Hydrops fetalis; ichthyosis | SNGP, strabismus opisthotonus, trismus | SNGP; myoclonic seizures; mild visceral involvement | SNGP; massive hepatosplenomegaly growth retardation | SNGP; cardiac valve calcifications; mild visceral involvement |
| Neurologic involvement | Early-onset parkinsonism or peripheral neuropathy (rarely) | Early-onset Parkinsonism or peripheral neuropathy (rarely) | Lethal | Severe | SNGP; slowly progressive neurologic deterioration | SNGP; gradual but progressive cognitive deterioration | SNGP; brachycephalus |
| Bone involvement | None | Mild to severe (variable) | None | None | Mild | Moderate to severe; kyphosis (gibbus) | Minimal in most; gibbus in the longest living |
| Lung involvement | None | None to (rarely) severe | Severe | Severe | Mild to moderate | Moderate to severe | Minimal |
| Life expectancy (if untreated) | Normal | Normal/near normal | Fetal/neonatal death | Death before 2 y | Death during childhood | Death in mid adulthood | Death in very early adulthood |
| Disease-specific treatment (2010) | None | ERT (or SRT if ERT unsuitable/not a therapeutic option) | None | Supportive (ERT not justified ethically) | ERT for visceral disease | ERT for visceral disease | Cardiac valve replacement if possible |
SNGP indicates supranuclear gaze palsy; ERT, enzyme replacement therapy; SRT, substrate reduction therapy; and PC, pharmacological chaperone.