Table 1.
Presenting features of all four children with mucopolysaccharidosis type II
| Patient | 1 | 2 | 3 | 4 |
|---|---|---|---|---|
| Presenting features | Macrocephaly, abdominal distension, coarse facial features, macroglossia, cardiac murmur | Speech delay, coarse facial features, recurrent respiratory tract infections | Coarse facial features, hepatomegaly, macrocephaly, hydrocephalus | Macrocephaly, developmental delay, enlarged adenoids and tonsils, cardiac murmur, coarse facial features |
| Age at presentation | 3 years 6 months | 3 years | 8 months | 3 years 8 months |
| Age at diagnosis | 3 years 6 months | 3 years | 8 months | 4 years 7 months |
| IDS enzyme activity (pmol/min/mg protein: normal range 10–88) | 1.8 | 0.26 | 0.03 | 0.4 |
| Genotype | c. 692C>G p. Pro231Arg |
c. 1327C>T p. A rg443* |
c. 57del p. Val20Ser |
c. 257C>T p. Pro86Leu |
| Predicted effect on IDS | Deleterious missense (highly conserved residue in the sulfatase protein domain) | Premature stop codon | Frameshift mutation | Activates multiple cryptic splice sites, resulting in aberrantly spliced transcripts |
| Height (centile) | 25th–50th | 95th | 50th | 60th |
| Weight (centile) | 75th–90th | 90th | 95th | 90th |
| Head circumference (centile) | >99th | 75th | 90th | >95th |
| Liver size (cm) | 14 | 14.3 | 6 | 10 |
| MRI brain | “Innumerable dilated perivascular spaces…honeycombed like appearance of the cerebral white matter” | Not performed | “Extensive but mild prominence of the perivascular spaces throughout the white matter,” abnormal high white matter signal in occipital lobes, age-appropriate myelination | “Extensive white matter changes in the left frontal lobe with multiple cyst-like spaces involving the subcortical white matter. Enlarged perivascular spaces in the white matter, especially the corpus calIosum. White matter volume slightly reduced but normal signal return” |
| Seep study | Not performed | Apnea-hypopnea index 24.5 events/h, minimum oxygen saturation 93% | Apnea-hypopnea index 9.9 events/h, minimum oxygen saturation 85% | Infrequent brief desaturations, otherwise normal |
| Previous operations | Hypospadias repair | Adenoidectomy, insertion of grommets | Left inguinal hernia repair | Tonsillectomy, adenoidectomy, grommet insertions (twice) |