Rescue of Infants With MCT8 Deficiency

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Rescue of Infants With MCT8 Deficiency Under Emergency Use Single Patient Expanded Access Treatment

Conditions
-----------------
Mct8 (Slc16A2)-Specific Thyroid Hormone Cell Transporter Deficiency

Intervention / Treatment
-----------------
* Drug: Diiodothyropropionic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 3 Days
Maximum Age: 3 Days

Sexes Eligible for Study
-----------------
Male

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Diiodothyropropionic acid|Drug Administration|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |