Letter to the editor on “Evidence for dopaminergic denervation in classical galactosemia”

Abstract

We read with interest the report by Poisson and colleagues, concluding that rest tremor in classical galactosemia may be linked to dopaminergic denervation. 1 The authors describe a galactosemia patient who in his mid-50s was found to have a parkinsonian phenotype and a striatal reduction in 123 I-FP-CIT DAT uptake. 1 Based on our own "new observation," reported below, we concur that striatal dopaminergic denervation may indeed be present in the late-onset tremor seen in galactosemia, although in our case the tremor was of the more typical postural and kinetic type than the predominantly rest tremor described by Poisson. 1,2 A 40-year old right-handed woman was referred to our center for consideration of deep brain stimulation for treatment of tremor that had reached a severity rendering her no longer able to feed, wash, or dress herself. Tremor of the head and tongue was causing progressive swallowing difficulties. She had been born after a normal pregnancy from nonconsanguineous parents and was diagnosed with classical galactosemia at 10 days of age after staphylococcal septicemia. Despite dietary restriction, she exhibited psychomotor developmental delay and ovarian failure. Since the age of 30 she had suffered progressively worsening dystonia and tremor. In addition to generalized dystonic posturing, clinical examination revealed a severe, low-frequency, wideamplitude, flexion-extension, asymmetric, rest, postural, and kinetic tremor involving the upper more than the lower limbs. The limb tremor involved both the proximal and the distal segments and had an added element of intention tremor. The head tremor disappeared with full head support. There was a mild degree of rigidity in both upper limbs but no bradykinesia.Given that the tremor phenomenologically most resembled Holmes tremor, for which L-dopa is known to be partially effective, 3 a trial of dispersible L-dopa 1 benserazide was initiated. Immediate benefit was observed even on low starting doses (L-dopa 150 mg per day), with complete resolution of the head and tongue tremor and 75% improvement of limb action tremor on L-dopa 450 mg per day. After 3 months, the patient developed wearing-off phenomena with breakthrough tremor at the end of each dosing period, necessitating an additional fourth dose. On one occasion when she attended clinic, her latest L-dopa dose had not yet kicked in, and she was exhibiting the same severe postural and kinetic tremor. Thirty minutes later as she switched "on," she demonstrated brief oromandibular dystonia, following which her head tremor entirely resolved and the limb tremor was markedly improved (see video).It is worth noting that although the case presented by Poisson showed evidence of presynaptic dopaminergic degeneration, indicating nigrostriatal dysfunction, they saw only a minimal response to L-dopa. 1 However, our patient with a tremor phenotype more suggestive of Holmes tremor 3 is likely to have involvement of the cerebellothalamocortical and/or dentaterubro-olivary pathways as well as the nigrostriatal trac...

Brain function in classic galactosemia, a galactosemia network (GalNet) members review

“…Although the aforementioned abnormalities could help explain the neurocognitive profile, the possibility of a coexistent disorder should always be considered, especially in case of unexpected symptoms ( Papachristoforou et al, 2014 ; Neville et al, 2016 ; Boca and Whone, 2017 ; Rossi-Espagnet et al, 2021 ).…”