A 7-month-old boy was referred with developmental delay and axial hypotonia (video 1). Screening for inborn errors of metabolism was negative and single nucleotide polymorphism array was normal (46,XY). Myotonic dystrophy (type 1) and spinal muscular atrophy were excluded. Whole exome sequencing yielded biallelic mutations in the tyrosine hydroxylase gene (c.698 G>A, p.Arg233His and c.1211C>T, p.Thr404Met). Subsequent CSF analysis revealed a significantly lowered homovanillic acid/5-hydroxyindoleacetic acid ratio, confirming tyrosine hydroxylase deficiency.1 Treatment with monotherapy levodopa resulted in profoundly improved motor development (video 1). After several weeks of treatment, the patient developed levodopa-induced dyskinesias (video 1),2 insomnia, and hyperactive behavior. All symptoms ameliorated with levodopa reduction.
Video 1
Improvement in motor development after start of levodopa in tyrosine hydroxylase deficiency. Part 1 shows a lack of antigravity movements and myoclonias of the legs during crying. Parts 2 and 3 are shortly after commencing treatment with levodopa at the age of 1 year (levodopa doses ±1.5 and ±2.5 mg/kg/d). Part 2 demonstrates opisthotonic posturing and limb dystonia. Part 3 shows bradykinesia with increased antigravity movements and chorea of abdominal muscles. Part 4 shows the patient at 16 months old; note the generalized dyskinesias (levodopa dose ±3.5 mg/kg/d). At this time the parents also reported insomnia and excessive sweating. Part 5 shows the patient on high-dose levodopa (±5.7 mg/kg/d), with very active, unsteady gait and dyskinesias.Download Supplementary Video 1 via http://dx.doi.org/10.1212/011757_Video_1
Study Funding
No targeted funding reported.
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Acknowledgment
The authors thank the parents for their cooperation.
Appendix Authors
Footnotes
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Teaching slides links.lww.com/WNL/B343
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