Clinical analysis of nine infants with tyrosine hydroxylase deficiency / 中华神经科杂志

ABSTRACT

Objective:To explore the clinical characteristics of children with tyrosine hydroxylase deficiency (THD) in order to recognize this disease early as to optimize the treatment to improve the prognosis.Methods:A retrospective analysis was done on the clinical data of nine children with THD who were diagnosed at the Children′s Hospital of Fudan University from May 2018 to May 2020, including name, gender, age, age of onset, age of presentation, age of diagnosis, clinical manifestations, head imaging, tyrosine hydroxylase gene mutation, treatment, follow-up, and other results, which were classified according to Willemsen′s method, and the clinical characteristics were summarized and a literature review was carried out.Results:There were five males and four females with the age at onset ranged from newborn to two years and six months (median three months). The duration of diagnosis ranged from four months to five years and seven months (median nine months). The presenting symptom was motor retardation in seven cases. Clinical symptoms included hypokinesia in eight cases, limb dystonia in five cases, truncal hypotonia in four cases, dysphagia/dysarthria in four cases, oculogyric crises in four cases, tremor in three cases, rigidity in three cases, mask faces in three cases, bilateral ptosis in two cases, hypersalivation/sweating in two cases, diurnal fluctuation in two cases, myoclonic jerks in one case, and status dystonicus in one case. Cranial magnetic resonance imaging was normal in seven cases and non-specific in two cases (backward myelination in one case and bilateral ventricle enlargement and decreased white matter in another one). Eight tyrosine hydroxylase gene variants were found, including four missense variants, two frameshift variants, one shear variants and one nonsense variant, as well as three novel variants [c.1505_1518dup (p.R507Afs *23), c.1128_1138del (p.Q377Gfs *12), c.1058A>G(p.H353R)]. All patients were treated with levodopa and benserazide hydrochloride tables. The initial and maintenance doses of type A were 1.7-8.3 mg·kg -1·d -1 and 4.5-20.0 mg·kg -1·d -1, respectively. The initial and maintenance doses of type B were 1.7-12.5 mg·kg -1·d -1 and 4.6-12.0 mg·kg -1·d -1, respectively. In type A, four patients had dyskinesis which was relieved by decreasing the dose or maintaining the same dose of levodopa. One case of type B had dyskinesis which was self-resolving. Conclusions:Although the clinical manifestations of this disease are varied, the initial symptoms in children with onset within the first year of life are mostly hypokinesia, truncal hypotonia, and dystonia in limbs. It is recommended that children with THD, regardless of clinical type, should start at the minimum dose for easy segmentation in the range of 1.0-5.0 mg·kg -1·d -1, and the maintenance dose can be adjusted according to the individual response of the child. The incidence of dyskinesia of this disease is not low, but most can be treated by decreasing the initial dose and delaying the dosage rate.