Also known as: Parkinsonism, infantile, autosomal recessive; Dystonia, dopa-responsive, autosomal recessive; Dopa-responsive dystonia, autosomal recessive; Tyrosine hydroxylase deficiency; DYT5b, DYT-TH


1. The Disease:

A very rare neurometabolic disorder characterized by a spectrum of symptoms ranging from those seen in dopa-responsive dystonia (DRD) to progressive infantile encephalopathy.

2. The symptoms:

Segawa syndrome (SS) or Tyrosine hydroxylase (TH) deficiency is associated with a broad phenotypic spectrum. Based on severity of symptoms/signs as well as responsiveness to levodopa therapy and clinical phenotypes as: TH-deficient dopa-responsive dystonia (the mild form of TH deficiency), TH-deficient infantile parkinsonism with motor delay (the severe form), and TH-deficient progressive infantile encephalopathy (the very severe form). Lack of early signs or symptoms does not exclude the diagnosis.

TH-deficient dopa-responsive dystonia. Onset is between age 12 months and 12 years; initial symptoms are typically lower-limb dystonia and/or difficulty in walking. Diurnal fluctuation of symptoms (worsening of the symptoms toward the evening and their alleviation in the morning after sleep) may be present.

TH-deficient infantile parkinsonism with motor delay. Onset is between age three and 12 months. In contrast to TH-deficient DRD, motor milestones are overtly delayed in this severe form. Affected infants demonstrate truncal hypotonia and parkinsonian symptoms and signs (hypokinesia, rigidity of extremities, and/or tremor).

TH-deficient progressive infantile encephalopathy. Onset is before age three to six months. Foetal distress is reported in most. Affected individuals have marked delay in motor development, truncal hypotonia, severe hypokinesia, limb hypertonia (rigidity and/or spasticity), hyperreflexia, oculogyric crises, ptosis, intellectual disability, and paroxysmal periods of lethargy (with increased sweating and drooling) alternating with irritability.

3. Actions to take in case of early diagnosis:

Babies with a positive genetic test (having biallelic pathogenic variants in the TH gene) should be referred immediately to a paediatric neurologist for clinical evaluation.

SS is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Neurology Center Management is provided by multidisciplinary team.

All individuals with TH-deficient DRD demonstrate complete responsiveness to levodopa (with a decarboxylase inhibitor).

Individuals with TH-deficient infantile parkinsonism with motor delay demonstrate a marked response to levodopa. However, in contrast to TH-deficient DRD, the responsiveness is generally not complete and/or it takes several months or even years before the full effects of treatment become established. Some individuals are hypersensitive to levodopa and prone to side effects (i.e., dopa-induced dyskinesias which develop at initiation of levodopa treatment).

Individuals with TH-deficient progressive infantile encephalopathy are extremely sensitive to levodopa therapy. In this very severe form, treatment with levodopa is often limited by intolerable dyskinesias.

Agents/circumstances to avoid: metoclopramide and other related antidopaminergic agents.

Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information:

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