Table 1.
Summary of patient clinical features
| Subject 1 | Subject 2 | |
|---|---|---|
| ISCA2 variant (NM_194279.2) | c.229G>A p.Gly77Ser | c.229G>A p.Gly77Ser |
| Gender | Male | Female |
| Age of onset | 3 m | 6 m |
| Current age | 3 y 5 m | Deceased |
| Age at last clinic visit | 1 y 9 m | 9 m |
| Age at death | N/A | 9 m |
| Growth | ||
| Poor growth | + | + |
| Poor weight gain | + | − |
| Head circumference | 50th centile | Relative macrocephaly |
| Ophthalmologic | ||
| Optic nerve pallor | + | + |
| Visual impairment | + | + |
| Dysmorphic features | ||
| Low set ears | + | − |
| Broad nasal bridge | + | − |
| Respiratory | ||
| Frequent infections | − | − |
| Tracheostomy | − | − |
| Gastrointestinal | ||
| Feeding difficulties/aspiration | +/− | +/+ |
| Constipation | − | + |
| Nasogastric tube | + | − |
| Skeletal | ||
| Joint laxity | − | + |
| Short fourth metacarpals | − | + |
| Cutaneous toe syndactyly | − | + |
| Neurological | ||
| Development delays | + | + |
| Developmental regression | +, 6 m | +, 6 m |
| Expressive language | − | − |
| Hypotonia | +, truncal | +, truncal |
| Spasticity | + | + |
| Abnormal movements | − | − |
| Ambulation | − | − |
| Seizure | − | − |
| Radiological | ||
| Leukodystrophy | + | + |
| MRS | Elevated lactate peak | Elevated lactate peak |
| T1/T2 signal abnormalities | Increased T2 in WM of SUF, PVWM extending into PLIC, PB, and SP of CC and CP. | Diffuse T1 and T2 in WM of FP, OC, and both CBH |
| Abnormal signal DTT, ICP, and CWM | ||
| Abnormal T2 in CCJ to T11 cord | ||
| Metabolic | N/A | |
| CSF | ||
| Glycine | 43.0 μmol/l (1.9–10) | |
| Glutamate | 18 μmol/l (0–3.9) | |
| 5‐MET | 46 nmol/l (72–305) | |
| Lactate | 6.69 mmol/l (1.1–2.2) | |
| Plasma | ||
| Glycine | Normal | |
| Glutamate | Normal | |
| Other PAA | Normal | |
| Lactate | 1.84 mmol/l (0.7–2.1) | |
| Chitotriosidase | 500 nmol/hr/ml (0–150) | |
| Palmitoyl thioesterase | 12 nmol/hr/mg (17–139) | |
| B‐glucosidase | 143 nmol/hr/mg (163–378) | |
| Arylsulfatase A | 17 nmol/hr/mg (22–103) | |
| Urine | ||
| Glycine | 2,393 μmol/l (92–760) | |
| Glutamate | 54 μmol/l (0–32) |
m, months; y, years; N/A, not applicable; MRS; functional magnetic resonance spectrometry; WM, white matter; SUF, subcortical U fibers; PVWM, periventricular white matter; PLIC, posterior limb of the internal capsule; PB, posterior body; SP, splenium; CC, corpus callosum; CP, cerebral peduncles; DTT, dorsal tegmental tracts; ICP, inferior cerebellar peduncles; CWM, cerebellar white matter; CCJ, craniocervical junction; FP, frontoparietal; OC, occipital; CBH, cerebellar hemispheres; CSF, cerebrospinal fluid; 5‐MET, 5‐methyltetrahydrofolate; PAA, plasma amino acids.