Table 1.
Clinical Characteristics
| Proband | I | II | III | IV | V | VI | VII |
|---|---|---|---|---|---|---|---|
| Age at assessment, years | 7.5 | 7.5 | 4.6 | 10 | 18 | 9.9 | 4.1 |
| Variant | |||||||
| Long isoform (NP_006508.1) | p.(Val566*) | p.(Val566*) | p.(Leu602HisfsTer680) | p.(Pro609GlnfsTer676) | p.(Pro609GlnfsTer676) | p.(His575Arg) | p.(Asn599Ser) |
| Short isoform (NP_006508.2) | p.(Val492*) | p.(Val492*) | p.(Leu528HisfsTer606) | p.(Pro535GlnfsTer602) | p.(Pro535GlnfsTer602) | p.(His501Arg) | p.(Asn525Ser) |
| Birth weight in grams (percentiles) | NA | NA | NA (p15) | 3080 (NA) | 2820 (NA) | 2780 (p4) | 3895 (p98) |
| Neurocognitive features | |||||||
| Dystonia | ++ | ++ | + | + | + | - | - |
| Spasticity | + | + | +/- | + | + | - | - |
| Hypotonia | ++ | ++ | + | + | + | +/- | - |
| Head circumference, cm (SD) | 52.5 (−0.0) | 51 (−1.1) | 51 (0.3) | 54.5 (1.0) | 52 (−2.8) | 47.5 (−4.2) | 50 (0.8) |
| Speech development | Absent | Absent | Some words | No verbal speech | No verbal speech | Few words | Sentences (delayed) |
| Head control | - | - | + | +/- | + | + | + |
| Sitting independently | - | - | +/- | - | - | + (11 m) | + |
| Walking independently | - | - | - | - | - | + (4y6m) | + (22 m) |
| Delay in achieving motor milestones | Severe | Severe | Severe | Severe | Severe | Severe | Mild |
| GMFM-G88 score (%)1 | 7 | 8 | 29.7 | ND | ND | ND | ND |
| IQ score (test) | ND | ND | ND | ND | ND | ND | ND |
| Psychiatric symptoms | ND | ND | - | Irritability | Irritability, aggressive | - | - |
| EEG-proven seizures | - | - | - | + | + | + | - |
| Feeding problems | + | + | + | + | + | + | - |
| Brain MRI abnormalities | Delayed myelination | Delayed myelination | - | - | PV WMHI, choroid cyst | - | - |
| Biochemical features | |||||||
| Total T3 in nmol/L (NR) | 6.4 (2.0-3.3) | 4.38 (2.0-3.3) | 3.47 (1.61-3.20) # | 3.05 (1.6-3.0)* | 3.73 (2.0-3.3) ‡ | 2.44 (2.0-3.3) * | 2.26 (2.0-3.3) † |
| Total T4 in nmol/L (NR) | 54 (74-151) | 41 (74-151) | 42.5 (57.9-154.5) # | 79 (62-136)* | 57 (74-151) ‡ | 81 (74-151)* | 82 (74-151) † |
| Free T4 in pmol/L (NR) | 6.6 (13-26) | 6.4 (13-26) | 11.6 (11.6-18) # | 12.3 (12-24)* | 9.7 (13-26) ‡ | 15.6 (13-26) * | 17.6 (13-26) † |
| Total rT3 in nmol/L (NR) | 0.11 (0.2-0.5) | 0.10 (0.2-0.5) | 0.08 (0.12-0.38) # | 0.19 (0.2-0.5)* | 0.11 (0.2-0.5) ‡ | 0.37 (0.2-0.5)* | 0.24 (0.2-0.5) † |
| TSH in mU/L (NR) | 4.42 (0.6-5.6) | 5.19 (0.6-5.6) | 3.02 (0.5-4.3) # | 1.22 (0.6-5.2) * | 3.90 (0.6-5.6) ‡ | 0.94 (0.6-5.6)* | 2.47 (0.6-5.6) † |
| SHBG in nmol/L (NR) | 275 (40-140) | 282 (40-140) | 163 (40-140) # | ND | 214.6 (40-140)** | 149.9 (40-140)* | ND |
| Total cholesterol in mmol/L (NR) | 2.1 (2.8-5.4) | 2.7 (2.8-5.4) | ND | ND | ND | ND | 4.0 (2.8-5.4) † |
| Peripheral features | |||||||
| Tachycardia in rest | - | - | + | ND | ND | - | - |
| Body weight in kg (SD) | 21.2 (−1.5) | 22.0 (−1.2) | 14.5 (−1.6) | 25 (−1.5) | 26.5 (−8.5) | 19.5 (−3.2) | 17.8 (0.1) |
| Body height in cm (SD) | 115 (−2.6) | 115 (−2.6) | 109 (0.2) | 133.5 (−0.8) | 137 (−4.0) | 123.4 (−1.9) | 107.5 (0.3) |
| BMI in kg/m2 (SD) | 16.03 (0.5) | 16.64 (0.9) | 12.2 (−2.8) | 14.0 (−2.0) | 14.1 (<−3.0) | 12.8 (−2.7) | 15.4 (−0.1) |
| Increased perspiration | + | - | - | + | - | - | - |
| Diarrhea | - | - | - | - | - | - | - |
MCT8 variants are indicated based on the long isoform reference sequence (NP_006508.1), widely used in existing literature on MCT8 deficiency, and on the short isoform reference sequence (NP_006508.2), that is the novel approved reference sequence used in publicly available genetic databases.
Abbreviations: BMI, body mass index; NA, not available; ND, not determined; NR, normal range for age; PV WMH, periventricular white matter hyper-intensities; rT3, reverse triiodothyronine; SD, standard deviation; SHBG, sex hormone–binding globulin; T3, 3,3′,5-triiodothyronine; T4, thyroxine; TSH, thyrotropin (thyroid-stimulating hormone).
1 GMFM-G88 is Gross Motor Function Measure-G88 which assesses the gross motor function. Scores range from 0 to 100%, with higher scores indicating better motor function and where a 100% score is achieved by a healthy child of 4 years of age. Thyroid function tests at the age of 7.5 years (*), 5 years (†), 3 years (#) or 15 years (‡). SHBG at the age of 16 years (**). Z scores of anthropomorphic parameters are derived from national references growth curves.