{"id":22291,"date":"2022-08-31T08:16:29","date_gmt":"2022-08-31T08:16:29","guid":{"rendered":"https:\/\/catweb.ro\/babydetect\/?p=22291"},"modified":"2022-08-31T08:16:29","modified_gmt":"2022-08-31T08:16:29","slug":"segawa-syndrome-autosomal-recessive-th-gene","status":"publish","type":"post","link":"https:\/\/www.babydetect.be\/en\/segawa-syndrome-autosomal-recessive-th-gene\/","title":{"rendered":"Segawa syndrome, autosomal recessive – TH gene"},"content":{"rendered":"

Also known as<\/u><\/em>:<\/u> Parkinsonism, infantile, autosomal recessive; Dystonia, dopa-responsive, autosomal recessive; Dopa-responsive dystonia, autosomal recessive; Tyrosine hydroxylase deficiency; <\/em>DYT5b, DYT-TH<\/p>\n

OMIM#605407 https:\/\/omim.org\/entry\/605407<\/a><\/p>\n

1. The Disease:<\/h4>\n

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

2. The symptoms:<\/h4>\n

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.<\/em><\/p>\n

TH-deficient dopa-responsive dystonia<\/em><\/strong>. 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.<\/p>\n

TH-deficient infantile parkinsonism with motor delay<\/em><\/strong>. 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).<\/p>\n

TH-deficient progressive infantile encephalopathy. <\/em><\/strong>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.<\/p>\n

3. Actions to take in case of early diagnosis:<\/h4>\n

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.<\/p>\n

SS is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Neurology Center Management is provided by multidisciplinary team.<\/p>\n

All individuals with TH-deficient DRD demonstrate complete responsiveness to levodopa<\/u><\/em> (with a decarboxylase inhibitor).<\/p>\n

Individuals with TH-deficient infantile parkinsonism with motor delay demonstrate a marked response to levodopa.<\/u><\/em> 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).<\/p>\n

Individuals with TH-deficient progressive infantile encephalopathy are extremely sensitive to levodopa therapy<\/u><\/em>. In this very severe form, treatment with levodopa is often limited by intolerable dyskinesias.<\/p>\n

Agents\/circumstances to avoid:<\/u><\/em>\u00a0metoclopramide\u00a0and other related antidopaminergic agents.<\/p>\n

Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings.<\/p>\n

4. For more information:<\/h4>\n

Biblio :<\/strong><\/p>\n