We followed a patient with manganese transporter deficiency due to homozygous SLC30A10 mutations from age 14 years until his death at age 38 years and present the first postmortem findings of this disorder. The basal ganglia showed neuronal loss, rhodanine-positive deposits, astrocytosis, myelin loss, and spongiosis. SLC30A10 protein was reduced in residual basal ganglia neurons. Depigmentation of the substantia nigra and other brainstem nuclei was present. Manganese content of basal ganglia and liver was increased 16-fold and 9-fold, respectively. Our study provides a pathological foundation for further investigation of central nervous system toxicity secondary to deregulation of manganese metabolism.

A debilitating late-onset disorder of the premutation in the FMR1 gene is the neurodegenerative disorder fragile X-associated tremor ataxia syndrome (FXTAS). We report two patients with FXTAS who have a history of substance abuse (opiates, alcohol, and cocaine) which may have exacerbated their rapid neurological deterioration with FXTAS. There has been no case report regarding the role of substance abuse in onset, progression, and severity of FXTAS symptoms. However, research has shown that substance abuse can have a negative impact on several neurodegenerative diseases, and we propose that in these cases, substance abuse contributed to a faster progression of FXTAS as well as exacerbated white matter disease.

The fragile X-associated tremor ataxia syndrome (FXTAS) is caused by the premutation in FMR1 gene. Recent reports of environmental toxins appear to worsen the progression of FXTAS. Here we present a case of male adult with FXTAS and a long history of methadone use. The patient shows a faster progression in both symptoms of disease and MRI changes compared to what is typically seen in FXTAS. There has been no research regarding the role of narcotics in onset, progression, and severity of FXTAS symptoms. However, research has shown that narcotics can have a negative impact on several neurodegenerative diseases, and we hypothesize that in this particular case, methadone may have contributed to a faster progression of FXTAS as well as exacerbating white matter disease through RNA toxicity seen in premutation carriers.

No abstract