E449X mutation in the thyroid hormone receptor beta associated with autoimmune thyroid disease and severe neuropsychomotor involvement.
OBJECTIVE
To report the clinical and molecular aspects of a patient with a diagnosis of Resistance to Thyroid Hormone (RTH) harboring the E449X mutation associated with autoimmune thyroid disease and severe neuropsychomotor retardation.


METHODS
We present a case report including clinical and laboratory findings, and molecular analysis of a Brazilian patient with RTH.


RESULTS
A 23-year old male presented hyperactivity disorder, attention deficit, delayed neuropsychomotor development, and goiter. Since the age of 1 year and 8 months, his mother had sought medical care for her son for the investigation of delayed neuropsychomotor development associated with irritability, aggressiveness, recurrent headache, profuse sudoresis, intermittent diarrhea, polyphagia, goiter, and low weight. Laboratory tests revealed normal TSH, increased T3, T4, antithyroglobulin and antimicrosomal antibody titers. Increasing doses of levothyroxine were prescribed, reaching 200 microg/day, without significant changes in his clinical-laboratory picture. Increasing doses of tiratricol were introduced, with a clear clinical improvement of aggressiveness, hyperactivity, tremor of the extremities, and greater weight gain. Molecular study revealed a nonsense mutation in exon 10, in which a substitution of a guanine to tyrosine in nucleotide 1345 (codon 449) generates the stop codon TAA, confirming the diagnosis of RTH.


CONCLUSIONS
This patient has severe neuropsychomotor retardation not observed in a single previous report with the same mutation. This may reflect the lack of a genotype-phenotype correlation in affected cases with this syndrome, suggesting that genetic variability of factors other than beta receptor of thyroid hormone (TRbeta) might modulate the phenotype of RTH.
Gurgel
Maria Helane Costa
MH
Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Montenegro Junior
Renan M
RM
Magalhaes
Rejane Araujo
RA
Lima
Grayce Ellen da C Paiva
GE
Montenegro
Renan Magalhães
RM
Magalhães
Patricia Kunzle Ribeiro
PK
Maciel
Lea Maria Zanini
LM
D001327:Autoimmune Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype; D011595:Psychomotor Agitation / Q000175:diagnosis* / Q000188:drug therapy; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D018382:Thyroid Hormone Resistance Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D013963:Thyroid Hormones / Q000378:metabolism; D055815:Young Adult
D018389:Codon, Nonsense; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones