Objective: To describe the phenomenology of tremor in infantile parkinsonism due to dopamine deficiency.

Background: Parkinsonism in childhood is usually caused by genetic abnormality, including primary neurotransmitter (NT) disorders and neurodegenerative conditions. Early diagnosis is crucial since primary NT disorders have an etiological therapy, with higher efficacy when begun early. While clinical criteria for Parkinson’s Disease in adulthood are well established, there is no consensus in childhood. This is critical for ages 0-3, when disease phenomenology may be difficult to identify in the context of more broad abnormalities in the developing motor system. Hypotonia, lack of postural development, global delay, hypokinesia, tremor, and dystonia are core signs of NT deficiency. Tremor phenomenology have been poorly explored.

Methods: We report 5 patients with NT deficiency presenting with jerky tremor in the first months. Tremor was the most concerning symptom for parents prompting medical evaluation. All patients underwent extensive work up including measurement of plasma prolactin and cerebrospinal fluid NT metabolite and pterin levels (4/5 pts) and genetic study. All had significant reduction of homovanillic acid and a variable degree of prolactin increase. The diagnosis included: Tyrosine Hydroxylase Deficiency (3), Sepiapterin Reductase Deficiency (1), and a likely pathogenic de novo mutation in CHRNA6 gene (1). Tremor was videoed before starting L-dopa and videos evaluated by four independent pediatric movement disorder experts.

Results: A bilateral high amplitude low frequency (3-5 Hz) upper limb rest and action tremor, eventually spreading to the whole body onset between 2 and 8 months and resolved after 2 to 6 months. The tremor was paroxysmal or continuous and in two cases was interruptible by voluntary movement or contact. The occurrence was age specific and in some cases subsided spontaneously before treatment. In others it rapidly responded to L-dopa. Other motor features included dystonia, hypo- and bradykinesia and motor delay.

Conclusions: Regardless of etiology, early dopamine defects may present with an age-specific low frequency, high amplitude tremor that may be self-limited. Tremor disappearance may be influenced by the maturation of descending motor pathways. This feature may act as an early marker for this group of disorders, facilitating diagnosis and enabling provision of timely and proper treatment.

References: Grattan‐Smith, P. J., Wevers, R. A., Steenbergen‐Spanjers, G. C., Fung, V. S., Earl, J., & Wilcken, B. (2002). Tyrosine hydroxylase deficiency: clinical manifestations of catecholamine insufficiency in infancy. Movement disorders, 17(2), 354-359. Kurian, M. A., Gissen, P., Smith, M., Heales, S. J., & Clayton, P. T. (2011). The monoamine neurotransmitter disorders: an expanding range of neurological syndromes. The Lancet Neurology, 10(8), 721-733.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/high-amplitude-jerky-tremor-in-developmental-dopamine-deficiency/