Endocrine Abstracts

Introduction: Thyroid gland pathology ranks first among endocrine diseases in children in Ukraine, and a similar trend has been observed over the last 20 years. In 2018y the prevalence of diffuse goiter was 277,708 patients (36.47 per 1000 population), nodular goiter - 2,311 patients (0.30:1000), diffuse toxic goiter - 341 patients (0.04:1000) and 129 cases of thyroid cancer (1.7:100,000). However, the Allan-Herndon-Dudley Syndrome is extremely rare and has not been previously diagnosed.

Case presentation: The child first visited an endocrinologist at 2y 4 months of age with complaints on tetraparesis, spasticity, mental retardation, developmental delay, vomiting and bilateral inguinal cryptorchidism. TSH was normal, but fT4 was low 0.48 ng/dl (N 1.1-2.0) and 25 mg of L-thyroxine was prescribed. At the age of 3, he still had low fT4 level (0.9 ng/dl), but elevated fT3 (6.8 pg/ml (N 2.7-5.2)). Based on the low fT4 L-thyroxine dosage was increased to 37.5 mg/day. Thereafter fT4 remained low (0.6 ng/dl), but fT3 increased to 9.3 pg/ml. Brain MRI revealed signs of periventricular leukomalacia, impaired myelination of the brain, internal and external non-occlusive hydrocephalus, hypoplasia of the corpus callosum, enlargement of the cistern magna and Dandy-Walker malformation. At 6 y.o. his height was normal, but weight was 12,8 kg (<5 p.c.). Genetic testing (tNGS panels) identified hemizygous pathogenic SLC16A2 c.940C>T (p.Arg314*) and KIF7 c.877dup (p.Gln293Profs*170)/c.2344C>G (p.Arg782Gly), inherited from unaffected parents. Following these results T3 analogue, Triac therapy was initiated, and after 9 months of dose titration normalization of T3/fT3 occurred. This therapy also resulted in a decrease in fT4 (0.22 ng/dl) and T4 to 1.57 mg/ml (N 7.6-13.7), however despite this, the patient had no symptoms of hypothyroidism, vomiting stopped, heart rate and BP normalized, and also weight gain occurred (+6 kg over 10 months of therapy), but there was no improvement in neurological status.

Conclusion: Despite the SLC16A2 gene is associated with X-linked SLC16A2-specific thyroid hormone cell transporter deficiency, also known as hereditary spastic paraplegia 22 and Allan-Herndon-Dudley syndrome causing severe neurological impairment, specific changes in thyroid hormones and poor prognosis, requiring Triac initiation therapy as early as possible, advanced genetic diagnostics is also necessary to identify a potential double hit that may exacerbate the underlying disease.