Product information and disease description Place of product in therapy Disease description

Diagnosis

9 evidence topics · 11 sources

Guideline recommendations for diagnostic evaluation and SLC16A2 sequencing

“When considering a diagnosis of MCT8 deficiency, we recommend a full clinical assessment to determine whether the patient exhibits any recognized clinical phenotypes and a physical examination, including neurological assessment” (opens the source at this quote in a new tab)
“If MCT8 deficiency is suspected, we recommend additional investigations including (but not limited to) serum (free) T3, (free) T4, reverse T3 (rT3) and TSH concentrations (interpreting results in the context of age-specific reference intervals)” (opens the source at this quote in a new tab)
“We recommend that SLC16A2 sequencing be performed in any male patient with: the following ‘major criteria’; typical biochemical profile (TSH within normal range or mildly raised, low or low-normal (F)T4, raised (F)T3, low reverse T3, and/or elevated (F)T3/(F)T4 or T3/rT3 ratio) in combination with either global developmental delay, hypomyelination on MRI, clinical signs of movement disorder (e.g. dystonia, bradykinesia), persistent primitive reflexes, or a positive family history for MCT8 deficiency” (opens the source at this quote in a new tab)
“Definitive diagnosis of MCT8 deficiency requires identification of a known pathogenic mutation, either by reliable in silico prediction and/or functional studies of novel variants in transfected cells or patient-derived cells.” (opens the source at this quote in a new tab)

Diagnostic and genetic criteria

“The diagnosis of AHDS is established in a male proband with suggestive findings and a hemizygous SLC16A2 pathogenic variant identified by molecular genetic testing, and in a female proband by identification of a heterozygous pathogenic variant in SLC16A2.” (opens the source at this quote in a new tab)
“All males with SLC16A2 pathogenic variants had high serum T3 concentration and, when obtained, low serum rT3 concentration.” (opens the source at this quote in a new tab)

Free T3 to free T4 ratio as a screening biomarker: Japanese nationwide survey

“The significantly higher value of the free T3/free T4 (fT3/fT4) ratio found in our study can be a simple and useful diagnostic biomarker (Our value 11.60 ± 4.14 vs control 3.03 ± 0.38).” (opens the source at this quote in a new tab)
“We created a receiver operating characteristic (ROC) curve from our data (27 genetically diagnosed cases) and Oto et al.’s data (129 controls) and confirmed that the sensitivity was 96.2 % and the false positive rate was 0 at cutoff values of 4, 4.5 and 5.” (opens the source at this quote in a new tab)

Free T3 to free T4 ratio as a screening biomarker: Turkish multicentre cohort

“In this multicenter, retrospective, cross-sectional study, the genetic characteristics and clinical data of twenty-one cases of genetically confirmed MCT8 deficiency were evaluated. The median age at the diagnosis was 2.4 (1.29; 5.9) years, which ranged from 0.5 to 14.0 years.” (opens the source at this quote in a new tab)
“In this study, with the exception of three cases with fT3/fT4 ratios of 4.95, 3.58, and 4.52, all cases exhibited fT3/fT4 ratios higher than five (9.9 (7.9; 12.0)).” (opens the source at this quote in a new tab)

Free T3 to free T4 ratio threshold in a monitoring guideline

“Calculating the free (F)T3/FT4 ratio is a readily accessible, cost-effective, and rapid test; a value exceeding 0.75 or above the 97th percentile strongly suggests MCT8 deficiency” (opens the source at this quote in a new tab)

Newborn screening and neonatal biomarkers

“Newborn screening, which is established to detect congenital hypothyroidism, is typically based on TSH concentration and does not currently include measurement of FT3. However, TSH is often within the reference range in newborns with MCT8 deficiency.” (opens the source at this quote in a new tab)
“Low reverse T3 (rT3) and a high T3/rT3 ratio have been identified in newborns with MCT8 deficiency, but this test is neither routinely offered in clinical practice nor regularly performed” (opens the source at this quote in a new tab)

Dried blood spot reverse T3 at birth

“Contrary to characteristic iodothyronine abnormalities of MCT8 deficiency during later life, T3 and T4 values were not discriminatory from those of other study groups. In contrast, rT3 was significantly lower.” (opens the source at this quote in a new tab)
“rT3 and T3/rT3 ratio in DBS samples obtained from neonates can serve as biomarkers to detect MCT8 deficiency at birth.” (opens the source at this quote in a new tab)

Diagnostic delay: international natural-history cohort

“Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0).” (opens the source at this quote in a new tab)

Diagnostic delay and alternative diagnoses: international parent registry

“The median reported age of onset of symptoms was 4 months (range, 1-13 months; Supplementary Fig. S5) (11), whereas the median age of diagnosis was 18 months (range, 4-312 months), indicating a median diagnostic delay of 14 months (range, 0-311 months).” (opens the source at this quote in a new tab)
“Median diagnostic delay was significantly shorter in patients born in or after 2017 vs before 2017 (8 vs 19 months, P < .0001).” (opens the source at this quote in a new tab)
“Reported alternative diagnoses (total n = 6) were cerebral palsy (n = 4), Pelizaeus-Merzbacher (like) disease (n = 1) and mitochondrial disease (not otherwise specified, n = 1).” (opens the source at this quote in a new tab)