Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

Resultados do tratamento da ambliopia com levodopa combinada à oclusão / Results of amblyopia treatment with levodopa associated with occlusion therapy

OBJETIVO: Verificar a melhora da acuidade visual com levodopa/benzerazida combinada à oclusão parcial e seguida por oclusão total, em pacientes com ambliopia considerada irreversível. MÉTODOS: Realizou-se estudo experimental aberto, envolvendo 37 pacientes entre 7 e 40 anos de idade, com ambliopia por estrabismo ou anisometropia, durante 9 semanas. Todos os pacientes foram tratados com levodopa (0,70 mg/kg/dia) e benzerazida 25 por cento associada à oclusão de 4 horas/dia do olho dominante por 5 semanas e, nas 4 semanas seguintes foi realizada somente a oclusão total (24 h) do olho dominante. A acuidade visual foi medida na tabela do ETDR (Early Treatment Diabetic Retinopathy) com escala logMAR (logaritmo do mínimo ângulo de resolução) antes de iniciar o tratamento e após 1, 3, 5 e 9 semanas de tratamento. As adesões ao tratamento de oclusão e a ingesta do me-dicamento foram verificadas por meio de questionário e pela contagem das cápsulas. Os efeitos adversos foram avaliados por exame clínico e questionário. RESULTADOS: Após 9 semanas de tratamento, a acuidade visual média melhorou em logMAR de 0,58 ± 0,16 para 0,23 ± 0,16 (melhora de 4 linhas na tabela ETDR). CONCLUSAO: Levodopa, na dose de 0,70 mg/kg/dia, é bem tolerada e associada à oclusão produz melhora significativa na acuidade visual de pacientes com ambliopia considerada irreversível.

Un nuevo preparado de levodopa benserazida en parkinsonianos con fluctuaciones motoras refractarias a tratamientos con L-dopa standard / [A new levodopa benserazide preparation for Parkinson’s disease with motor fluctuations refractory to standard L-dopa]

As Parkinson’s disease worsens, many patients develop motor fluctuations which usually correlate directly or indirectly with L-dopa plasma levels. A new L-dopa-benserazide HBS preparation (Madopar) a control release pharmaceutical formulation which is activated when it contacts gastric fluid thus providing more stable L-dopa plasma levels, was assayed. Ten patients with a diagnosis of idiopathic Parkinson’s disease and motor fluctuations otherwise unresponsive to conventional therapy were selected. The average age was 62 years and the duration of the disease 9 years. The motor status was evaluated on an hourly basis with the King’s College Parkinson’s disease rating scale; in addition, a nocturnal disability scale (Lees) was used. Out of the 10 patients, 2 dropped out within the first month due to worsening of parkinsonian signs, while 7 of the remainders preferred HBS preparation to the previous treatment. The number of off hours in this group was reduced by 58

and motor fluctuation became less severe. In only 3 cases was it possible to use HBS as monotherapy while in the rest standard L-dopa had to be added, specially as morning doses. The average L-dopa daily dose was increased by 36

. Unwanted effects included psychiatric disturbances in two (in one L-dopa dose had to be reduced) and epigastralgia in one. Our findings suggest that this L-dopa-benserazide control release may be considered an able therapeutic formulation in the control of motor fluctuations in Parkinson’s disease.