INFORMATION SHEET

L-TYROSINE SUPPLEMENTATION

IN

NEMALINE MYOPATHY

Updated May 2013 by:

Dr Sarah Sandaradura, INMR
Initial document prepared by:
Prof K North, Honorary Consultant, INMR.

Corner Hawkesbury Road

and Hainsworth Street
Locked Bag 4001
Westmead NSW 2145
Sydney Australia
DX 8213 Parramatta
Tel +61 2 9845 0000
Fax +61 2 9845 3489
www.chw.edu.au
ABN 53 188 579 090

Nemaline myopathy usually presents in infancy or early childhood with weakness of the facial, bulbar,
proximal limb and respiratory muscles. Bulbar dysfunction in nemaline myopathy causes swallowing
difficulties and drooling, and may predispose to aspiration of oral secretions.
There is currently no curative treatment available for patients with nemaline myopathy. Treatment strategies
are largely empirical and symptomatic. Of interest is a case report of an 11 year old boy with nemaline
myopathy, in which L-tyrosine therapy lead to a dramatic and reproducible improvement in muscle strength,
appetite and weight gain. Within 48 hours of commencement of treatment there was a profound improvement
in pharyngeal secretions and drooling (Kalita 1989).
Based on this report we have given a number of patients with nemaline myopathy dietary supplementation
with L-tyrosine. Ryan et al recently reported outcome in five patients (four infants and one adolescent)
treated with L-tyrosine (Ryan et al. 2008). All four infants were reported to have an initial decrease in drooling
and secretions and an increase in energy levels. The adolescent showed improved strength and exercise
tolerance. No adverse effects of treatment were noted. These initial observations suggest that dietary
tyrosine supplementation may improve bulbar function, activity levels and exercise tolerance in nemaline
myopathy.
A recent study of a mouse model of nemaline myopathy (Acta1(H40Y) knock-in mice) suggested that use of
L-tyrosine may be beneficial in NM. In this mouse model, administration of L-tyrosine lead to improvements
in strength and mobility and fewer abnormalities on skeletal muscle biopsy (Nguyen et al, 2011),
Tyrosine is a non-essential amino acid that the body normally derives from two sources, diet and the
chemical breakdown of phenylalanine in the liver. Tyrosine is converted to L-dihyroxyphenylalanine (L-Dopa)
by tyrosine hydroxylase. This forms the rate-limiting step in the synthesis of the catecholamines dopamine,
norepinephrine and epinephrine. These compounds are important neurotransmitters and are involved in the
regulation of motor co-ordination, behaviour, learning, memory, sleep-wake cycle regulation endocrine and
visceral functions and arousal in adults. An exhaustive search of the medical literature has not revealed any
side effects related to treatment with L-tyrosine using doses up to 300mg/kg/day.
The reason for the clinical improvements in patients with nemaline myopathy treated with L-tyrosine is not
clear. It is possible that tyrosine directly dries up saliva to improve handling of oral secretions. It may act on
the brain to increase stamina or may act on the peripheral muscle motor unit response to improve the
efficiency of muscle function. Further studies in mouse models of nemaline myopathy may provide insight
into the mechanism of action. In the meantime, larger and placebo controlled clinical trials are needed to
establish that L-tyrosine is truly effective in the therapy of patients with nemaline myopathy.
In the children we treat in Australia, we perform plasma amino acid analysis prior to treatment to exclude a
coexisting disorder of tyrosine or phenylalanine metabolism. All children in the study reported by Ryan et al
underwent baseline and follow-up testing of liver function, plasma amino acid levels, serum ammonia and full
blood count. L-tyrosine was administered in powdered form or capsules (Musashi Australia). The optimal
dose of tyrosine is unknown. In the study by Ryan et al, initial dose in the four infants was 250mg-

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500mg/day or approximately 50mg/kg/day. In this study, dose was increased by 500mg at monthly intervals if
patients experienced a positive response with no side effects. In the single adolescent patient in this study,
dose was 1.5g twice daily. Doses greater than 250mg per day are usually given as twice daily doses (eg
500mg given as 250mg twice daily).
Suggested doses, based on this study and on experience with this medication, are as below:
<2 years of age starting dose 250-500mg/day, increase by 250-500mg after 2-4 weeks, depending on
response and side effects, to a total maximum dose of 1.5g per day
2-10 years of age - starting dose 250-500mg/day, increase by 250-500mg after 2-4 weeks, depending on
response and side effects, to a total maximum dose of 3g per day
>10 years of age starting dose 1g per day, increase by 500mg after 1-2 weeks, depending on response
and side effects, to a total maximum dose of 3g per day
Treatment should be monitored by the patients physician, and dose increases made only on the advice of
the treating physician.
For patients continuing to experience improving clinical effects at the maximum stated doses in the absence
of significant side effects, further dose increases above the stated maximum should be considered and dose
titrated to response and side effects.

References
Kalita D. A new treatment for congenital nonprogressive nemaline myopathy. Journal of Orthomolecular
Medicine 1989;2:70-74.
Nguyen MA, Joya JE, Kee AJ, Domazetovska A, Yang N, Hook JW, Lemckert FA, Kettle E, Valova VA,
Robinson PJ, North KN, Gunning PW, Mitchell CA, Hardeman EC. Hypertrophy and dietary tyrosine
ameliorate the phenotypes of a mouse model of severe nemaline myopathy. Brain 2011;134:3516-29.
Ryan MM, Sly C, Rudge S, Ellaway C, Ketteridge D, Roddick LG, Iannaccone ST, Kornberg AJ, North KN.
Dietary L-tyrosine supplementation in nemaline myopathy. J Child Neurology 2008 Jun;23(6):609-13.

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