Endokrinológia és anyagcserebetegségek (benne cukorbetegség, hormonok)
Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding
monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability
resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought
to systematically assess the phenotypic characteristics and natural history of patients
with MCT8 deficiency.We did an international, multicentre, cohort study, analysing
retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency
followed up in 47 hospitals in 22 countries globally. The key inclusion criterion
was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary
objective was to analyse the overall survival of patients with MCT8 deficiency and
document causes of death. We also compared survival between patients who did or did
not attain full head control by age 1·5 years and between patients who were or were
not underweight by age 1-3 years (defined as a bodyweight-for-age Z score <-2 SDs
or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive
function and outcomes, and clinical parameters including anthropometric characteristics,
biochemical markers, and neuroimaging findings.Between Oct 14, 2014, and Jan 17, 2020,
we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at
diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients
died; the main causes of mortality in these patients were pulmonary infection (six
[19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI
8·3-61·7). Individuals who did not attain head control by age 1·5 years had an increased
risk of death compared with patients who did attain head control (hazard ratio [HR]
3·46, 95% CI 1·76-8·34; log-rank test p=0·0041). Patients who were underweight during
age 1-3 years had an increased risk for death compared with patients who were of normal
bodyweight at this age (HR 4·71, 95% CI 1·26-17·58, p=0·021). The few motor and cognitive
abilities of patients did not improve with age, as evidenced by the absence of significant
correlations between biological age and scores on the Gross Motor Function Measure-88
and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were
above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine
concentrations were below the age-specific lower limit in 94 (89%) of 106 patients.
59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic
blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial
contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI
finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients.Our
description of characteristics of MCT8 deficiency in a large patient cohort reveals
poor survival with a high prevalence of treatable underlying risk factors, and provides
knowledge that might inform clinical management and future evaluation of therapies.Netherlands
Organisation for Health Research and Development, and the Sherman Foundation.
