Rescue of Infants With MCT8 Deficiency
Rescue of Infants With MCT8 Deficiency
MCT8 deficiency (that is also known as Allan-Herndon-Dudley syndrome) is a rare X-linked
 inherited disorder of brain development that causes severe intellectual disability and
 problems with movement.
MCT8 deficiency (that is also known as Allan-Herndon-Dudley syndrome) is a rare X-linked
 inherited disorder of brain development that causes severe intellectual disability and
 problems with movement. This condition, which occurs almost exclusively in males, disrupts
 development from before birth. There is no sucking reflex and the child has marked hypotonia.
 Developmentally, unlike normal infants, affected males are unable to turn over from belly to
 back. Individuals with identical mutations have identical phenotypes and all individuals,
 regardless of the phenotype have severe neuropsychological impairment. Diagnosis is confirmed
 by demonstration of a mutation in the MCT8 gene (1,2).

 MCT8-specific thyroid hormone cell-membrane transporter deficiency is characterized by severe
 cognitive deficiency, infantile hypotonia, diminished muscle mass and generalized muscle
 weakness, progressive spastic quadriplegia, joint contractures, and dystonic and/or athetoid
 movement with characteristic paroxysms or kinesigenic dyskinesias. Seizures occur in about
 25% of cases. Most affected males never sit or walk independently or lose these abilities
 over time; most never speak or have severely dysarthric speech (1). Brain MRI obtained in the
 first few years of life shows transient delayed myelination, which improves by age four years
 (3). Although psychomotor findings observed in affected males do not occur in heterozygous
 females, the latter often have thyroid test abnormalities intermediate between affected and
 normal individuals.
Inclusion Criteria:

 -  After confirmation of MCT8 gene mutation of the male fetus

 -  A child or children previously born with severe, typical phenotype and MCT8 gene
 mutation identical to that of the fetus to be treated in the mother or a sister who
 has a relative with known MCT8 defect

 -  Parental refusal to terminate the pregnancy

 Exclusion Criteria:

 -  Twin Pregnancy

 -  Election to terminate pregnancy

 -  Maternal hyperthyroidism requiring treatment

 -  Patient with significant liver or kidney insufficiency

 -  Congestive heart failure

 -  Hyperemesis unresponsive to treatment

 -  Significant maternal cardiac-related conditions (atrial fibrillation, other
 arrhythmia's, unstable angina coronary heart disease

 -  sympathomimetic therapy

 -  Anticoagulant therapy

 -  Patients taking Cytochrome P450 2C9 (CYP2C9) inhibitors with narrow therapeutic index