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IEMbase 0099: TH-related tyrosine hydroxylase deficiency

Scope

Field Value
IEMbase ID 99
Nosology 23.1.01.01
Gene TH
External IDs OMIM:191290
Generated mapping AMBIGUOUS
Candidate DisMech targets Autosomal_Recessive_Dopa_Responsive_Dystonia.yaml; Disorder_of_Catecholamine_Synthesis.yaml#Tyrosine hydroxylase deficiency; Dopa_Responsive_Dystonia.yaml#AR-DRD
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive TH-related tyrosine hydroxylase deficiency, with alternate labels L-dopa responsive dystonia and TH. Treatability is marked yes.

The characteristic biochemical rows are CSF MHPG, CSF HVA/5-HIAA ratio, and CSF homovanillic acid. The wider panel also includes CSF 5-HIAA, urinary dopamine, urinary homovanillic acid, urinary norepinephrine, urinary VMA, and plasma prolactin.

The characteristic clinical rows include bradykinesia, dystonia, hypokinesia, hypotonia, intellectual disability, oculogyric crisis, ptosis, rigidity, tremor, feeding difficulties, drooling, irritability and lethargy crises, sweating, temperature instability, sleep disturbance, growth retardation, epileptic seizures, and complicated perinatal course.

Treatment is L-dopa plus carbidopa.

DisMech phenotype coverage

The generated AMBIGUOUS status is understandable, but the canonical local target should be Autosomal_Recessive_Dopa_Responsive_Dystonia.yaml.

That file has the exact MONDO concept for TH-deficient dopa-responsive dystonia, TH biallelic pathogenic variants, tyrosine hydroxylase enzymatic deficiency, central dopamine biosynthesis impairment, infantile parkinsonism and progressive infantile encephalopathy subtypes, low CSF homovanillic acid, bradykinesia, hypokinesia, hypotonia, oculogyric crises, ptosis, rigidity, tremor, feeding difficulties, drooling/excessive salivation, sweating/night sweats, and levodopa with a decarboxylase inhibitor.

Dopa_Responsive_Dystonia.yaml#AR-DRD is useful group-level context. Disorder_of_Catecholamine_Synthesis.yaml#Tyrosine hydroxylase deficiency is useful pathway-umbrella context. Neither is as specific as the standalone TH-deficient AR DRD entry.

Concordance and completeness

Judgement: ambiguous generated mapping with high local disease-level coverage once the specific target is selected.

IEMbase is richer for neurotransmitter-panel detail, especially MHPG, HVA/5-HIAA ratio, urinary catecholamines, VMA, and prolactin. DisMech is richer for disease scope, subtype structure, pathophysiology, genetic evidence, and levodopa-response rationale.

Curation actions

  • Resolve this record to Autosomal_Recessive_Dopa_Responsive_Dystonia.yaml as the canonical target.
  • Keep Dopa_Responsive_Dystonia.yaml#AR-DRD and Disorder_of_Catecholamine_Synthesis.yaml#Tyrosine hydroxylase deficiency as secondary umbrella contexts.
  • Consider adding additional neurotransmitter biomarkers from IEMbase if the TH entry is expanded.