PARK2 Patient Presenting with Dopa-Responsive Dystonia.

We report a 34-year-old female PARK2 patient presenting with dopa-responsive dystonia (DRD). She noticed difficulty in raising her foot while walking at the age of 24. Her lower limb symptoms were identified as dystonia later, and she was started on Menesit, which resulted in improvement of her symptoms. She was diagnosed as DRD and has been on continuous treatment since then. The specific binding ratio (SBR) of 123I FP-CIT SPECT was significantly lower than those of controls of the same age, but 123I-meta-iodobenzylguanidine myocardial scintigraphy showed a normal heart to mediastinum ratio. The Montreal Cognitive Assessment, Japanese version, was normal for her age. DRD is an inherited dystonia that typically begins during childhood and may be caused by mutations of the GCH1 (GTP cyclohydrolase), SPR (sepiapterin reductase), or TH (tyrosine hydroxylase) genes. Our patient was diagnosed as PARK2, known as autosomal-recessive juvenile Parkinson's disease, based on genetic analysis. Although there was no family history of the disease, the decrease in SBR of 123I FP-CIT SPECT enabled us to diagnose PARK2 and to differentiate this from DRD due to other genetic disorders.

Mutation analysis of the PINK1 gene in 391 patients with Parkinson disease.

OBJECTIVES: To determine the frequency, distribution, and clinical features of Parkinson disease (PD) with PINK1 mutations. DESIGN: Retrospective clinical and genetic review. SETTING: University hospital. PATIENTS: We performed extensive mutation analyses of PINK1 in 414 PD patients negative for parkin mutations (mean [SD] age at onset, 42.8 [14.3] years), including 391 unrelated patients (190 patients with sporadic PD and 201 probands of patients with familial PD) from 13 countries. RESULTS: We found 10 patients with PD from 9 families with PINK1 mutations and identified 7 novel mutations (2 homozygous mutations [p.D297MfsX22 and p.W437R] and 5 single heterozygous mutations [p.A78V, p.P196QfsX25, p.M342V, p.W437R, and p.N542S]). No compound heterozygous mutations were found. The frequency of homozygous mutations was 4.26% (2 of 47) in families with autosomal recessive PD and 0.53% (1 of 190) in patients with sporadic PD. The frequency of heterozygous mutations was 1.89% (2 of 106) in families with potential autosomal dominant PD and 1.05% (2 of 190) in patients with sporadic PD. The mean (SD) age at onset in patients with single heterozygous mutations (53.6 [11.1] years; range, 39-69 years) was higher than that in patients with homozygous mutations (34.0 [20.3] years; range, 10-55 years). Myocardial iodine-123 metaiodobenzylguanidine uptake was low in patients with heterozygous mutations but not in those with homozygous mutations. CONCLUSIONS: Our results suggest that homozygous PINK1 mutations tend to be diagnosed as the early-onset autosomal recessive form of PD. Single heterozygous mutations may contribute to the development of sporadic PD and also could be an additional genetic predisposition for developing familial PD. The reduced myocardial iodine-123 metaiodobenzylguanidine uptake observed in patients with single heterozygous PINK1 mutations is similar to that seen in patients with sporadic PD.

Parkinson's disease and fatigue.

Fatigue is one of the most common symptoms in patients with Parkinson's disease (PD), and its impact on the quality of life is substantial. However, its cause and treatment are not established. Fatigue in PD has two components, peripheral and central, which may be related to each other, but are more likely independent. Fatigue is partially associated with depression or sleep disorders, but patients with fatigue are not always depressed and do not necessarily have sleep problems. Anti-PD drugs may exacerbate or reduce fatigue. The impact of fatigue in PD is often underestimated by health-care providers.