Table 1. Clinical and biochemical studies for patients 1-3.
| Patient 1 (GC15080) | Patient 2 (GC19954) | Patient 3 | |
|---|---|---|---|
| Sex, ethnicity | Male, Asian Pakistani | Female, Caucasian | Male, Caucasian |
| SUMF1 genotype | c. 290G>T; p.(Gly97Val) c.293T>A ; p.(Val98Glu) Homozygous for both variants | c.866A>G ; p.(Tyr289Cys) Homozygous | c.866A>G ; p.(Tyr289Cys) c.726-1G>C Compound heterozygous |
| Presenting symptom (age, y) | Reduced central vision (13) | Reduced reading vision (40s) | Multisystem (childhood) |
| Age at last examination (y) | 37 | 58 | 13 |
| Ocular features | |||
| BCVA (Snellen) | HM both eyes | 3/60 both eyes | 6/7.5 both eyes |
| Cornea | Clear | Endothelial guttata | Clear |
| Lens | Clear | Mild cataracts | Clear |
| Fundus | Central macular atrophy | Mild pigmentary changes at the central macula | Mild RPE mottling at posterior pole |
| Auto-fluorescence | Posterior pole hyper autofluorescence with central mottled hypo autofluorescence | Posterior pole hyper autofluorescence with central mottled hypo autofluorescence | Narrow perimacularring of hyperautofluorescence |
| OCT | Outer retinal disruption | Outer retinal disruption | Perifoveal loss of outer segment structure with a “bulls-ey” appearance |
| ERG | Severe generalised rod photoreceptor dysfunction with mild cone system involvement and severe macular involvement. Reduced DA3 & DA10 ERG b:a ratios (additional inner retinal rod system dysfunction) |
Severe generalised rod/cone photoreceptor dysfunction with severe macular involvement. Reduced DA3, DA10 and LA3 ERG b:a ratios and (additional inner retinal dysfunction) |
LA ERGs normal. DA10 ERG a-wave borderline. Reduced DA3 & DA10 ERG b:a ratios (inner retinal rod system dysfunction) |
| Other | - | Glaucoma, FCED | - |
| Non-ocular features | |||
| Cardiac evaluation | Not available | Echocardiography: LVH with normal systolic function, grade 1 diastolic dysfunction | Normal echocardiography |
| Abdominal evaluation | No organomegaly | Mild fatty liver and gallstones | Small kidneys, mildly enlarged liver with no intrahepatic lesions |
| Skeletal survey | No dysostosis multiplex | No dysostosis multiplex | Scoliosis and subtle thoracolumbar kyphosis. No dysostosis multiplex |
| Neuroimaging | No leukodystrophy, incidental pituitary microadenoma under investigation | Small vessel disease | Mild prominence of perivascular spaces and mild ventriculomegaly involving the lateral ventricles. No emergent features of MSD |
| Other features | - | - | Autism, oral aversion and feeding difficulties, short stature, recurrent ear and throat infections, mild OSA, hypermobility and POTS (EDS type 3) |
| Biochemical testing | |||
| Arylsulphatase A | ↓ ↓ | ↓ ↓ | ↓ ↓ |
| Heparin Sulphamidase | ↓ | ↓ | ↓ ↓ |
| Iduronate Sulphatase |
↓ | Normal | Normal |
| Galactose-6-sulphatase | Normal | Normal | Normal |
| N-acetyl glucosamine-6-sulphatase | Not available | Not available | ↓ ↓ |
| Urinary glycosaminoglycan | Presence of chondroitin sulphate, heparan sulphate and trace dermatan sulphate | Normal | Presence of chondroitin sulphate, heparan sulphate and dermatan sulphate |
Abbreviations: BCVA, best corrected visual acuity; DA, dark-adapted; ECG, electrocardiogram; EDS, Ehlers-Danlos syndrome; ERG, electroretinogram; FCED, Fuchs corneal endothelial dystrophy; LA, light-adapted; LVH, left ventricular hypertrophy; MSD, multiple sulfatase deficiency; OCT, optical coherence tomography, OSA, obstructive sleep apnoea, POTS, postural orthostatic hypotension syndrome, RPE, retinal pigment epithelium; y, year; ↓, reduced ; ↓↓, significantly reduced