To explore the clinical, examination characteristics, treatment and prognosis of hepatolenticular degeneration patients with atypical manifestation. Methods: Three cases of hepatolenticular degeneration were reported and the relevant literature were reviewed. Results: All three patients were concealed from middle age and worsened progressively and slowly. The neurological manifestations were different from each other. Case 1 presented with weight gain, cognitive impairment, dysarthria and limb weakness gradually. Case 2 showed progressive dysarthria. Case 3 presented with tremor and dysarthria. All the three patients presented with widespread cortical, pyramidal tract and extrapyramidal impairment with the development of the disease. The Kayser-Fleischer rings were detected in all of the patients, which had been discovered by slit-lamp in one patient. All of them had the hepatic impairment and low ceruloplasmin concentrations compared to the normal range (＜ 0.8 g/L). A patient showed abnormal coagulation function obviously. MRI abnormalities were multiple and bilateral symmetry, presented in basal ganglia and brainstem. The T1 weighted image revealed hypointensities and the T2/FLAIR weighted image also showed hyperintensities. The clinical symptoms of all the patients were significantly improved by low copper diet and penicillium and zinc sulfate.We collected data of 662 cases of hepatolenticular degeneration from the MEDLINE. Eight initial manifestations and four major clinical symptoms were summarized. And the causes of misdiagnosis were analyzed. Conclusion: Hepatolenticular degeneration progressive insidiously and slowly. Neuro-multisystem damage was common. Symmetrical abnormal signal was often found in brainstem and basal ganglia in MRI. To further clarify the diagnosis, Kayser-Fleischer rings, abdominal ultrasound and serum ceruloplasmin should be examined. Patients who received early diagnosis and treatment have a good clinical prognosis.