Parkin Disease

Abstract

Importance Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss. Objective To investigate whether parkin -linked parkinsonism is a different clinicopathologic entity to Parkinson disease (PD). Design, Setting, and Participants We describe the clinical, genetic, and neuropathologic findings of 5 unrelated cases of parkin disease and compare them with 5 pathologically confirmed PD cases and 4 control subjects. The PD control cases and normal control subjects were matched first for age at death then disease duration (PD only) for comparison. Results Presenting signs in the parkin disease cases were hand or leg tremor often combined with dystonia. Mean age at onset was 34 years; all cases were compound heterozygous for mutations of parkin. Freezing of gait, postural deformity, and motor fluctuations were common late features. No patients had any evidence of cognitive impairment or dementia. Neuronal counts in the substantia nigra pars compacta revealed that neuronal loss in the parkin cases was as severe as that seen in PD, but relative preservation of the dorsal tier was seen in comparison with PD (P = .04). Mild neuronal loss was identified in the locus coeruleus and dorsal motor nucleus of the vagus, but not in the nucleus basalis of Meynert, raphe nucleus, or other brain regions. Sparse Lewy bodies were identified in 2 cases (brainstem and cortex). Conclusions and Relevance These findings support the notion that parkin disease is characterized by a more restricted morphologic abnormality than is found in PD, with predominantly ventral nigral degeneration and absent or rare Lewy bodies.

A Peruvian family with a novel PARK2 mutation: Clinical and pathological characteristics

“…[10-20] Common pathologic features have included severe neuronal loss in the substantia nigra (SN), variable neuronal loss in the locus coeruleus (LC), and relatively rare Lewy body pathology. [20]…”

Olfaction in Parkin carriers in Chinese patients with Parkinson disease

“…Parkin related PD had clinical and pathologic features that might show varying degrees of difference with idiopathic PD (Doherty et al., 2013). Young onset age, more symmetric involvement, dystonia at presentation, brisk deep tendon reflexes, a good response to levodopa therapy (Lohmann et al., 2003; Lucking et al., 2000), and more symmetric and more marked reduction of dopamine uptake on 123I FP‐CIT SPECT scan (DaTSCAN) were found in Parkin ‐related disease (McNeill et al., 2013).…”

“…In PD, degeneration of the olfactory nucleus with impairment of smell starts early in Braak stageI(Braak et al., 2003) and was thought to be specific for Lewy body‐type neurodegeneration. The PD ‐Parkin patients had less extensive distribution of Lewy bodies neuropathology, that might not follow Braak staging and spares olfactory structures (Doherty et al., 2013; Gouider‐Khouja et al., 2003), and might explain their preserved olfaction. The absence of Lewy bodies in patients with Parkin mutations suggested that Parkin might be required for the formation of Lewy bodies.…”

“…Based on the special clinical and pathological features, Parkin mutation causing Parkinsonism has been postulated as a different disease entity compared to idiopathic PD (Doherty et al., 2013; Khan et al., 2004). While impaired olfaction was frequently associated with PD, olfactory identification was reported to be better among patients with Parkin mutations (Alcalay et al., 2011; Malek et al., 2016).…”

“…While impaired olfaction was frequently associated with PD, olfactory identification was reported to be better among patients with Parkin mutations (Alcalay et al., 2011; Malek et al., 2016). This was in line with pathologic findings in PD patients that Parkin mutation carriers showed less extensive distribution of Lewy bodies, which might not follow Braak staging and spares olfactory structures (Doherty et al., 2013; Gouider‐Khouja et al., 2003; Hayashi et al., 2000). …”