Dopa‐responsive dystonia (Segawa disease)‐like disease accompanied by mental retardation: A case report

The patient was a 20-year-old woman with no family history of neurological disorders. She was born without any abnormal developmental features. At the age of 2 years, she could speak only two words, and at the age of 3 years, her family noticed her mental retardation. Afterward, her posture gradually became stooped and all her movements slowed. At the age of 20 years, she was admitted to the hospital, because the aforementioned symptoms were continuing to worsen. She was initially diagnosed as having juvenile Parkinson disease. A physical examination did not reveal any abnormalities, except for her stooped posture. During a neurological examination, however, a lead-pipe rigidity throughout her entire body and extreme bradykinesia was observed. Her voice was too soft for her words to be understood. She did not exhibit tremor or other involuntary movements, and her symptoms had no diurnal fluctuation. Her general blood data were normal. A brain MRI showed no abnormal findings. WAIS-R test revealed an IQ of 44. HDS-R scores were 22 points. MMSE scores were 23 points. The level of neopterin in her cerebrospinal fluid (CSF) was extremely low (less than 1 nM). The levels of serum neopterin, biopterin, GTP cyclohydrolase I (GTPCH-I) activity, and serotonin were also low, compared with healthy controls (Table 1). 1 These data indicated a revised diagnosis of hereditary progressive dystonia with marked diurnal fluctuations/dopa-responsive dystonia (HPD/DRD; Segawa disease). 1–3 However, a genetic analysis to determine the cause of her Parkinsonism revealed no abnormalities (GTPCH-I and sepiapterin reductase genes). After treatment with low-dose levodopa (L-dopa) (20 mg/kg), her symptoms (stooped posture, rigidity, bradykinesia, and low voice) were clearly ameliorated, but no change in her mental retardation was observed. In many cases, HPD/DRD is inherited in a manner consistent with an autosomal dominant disorder with sex-related, reduced penetrance. This characteristic is caused by a mutation in the (GTPCH-I gene, the enzyme which catalyzes the first step in the biosynthesis of BH4.4 BH4 is a natural cofactor for three aromatic amino acid hydroxylases (tyrosine hydroxylase, tryptophan hydroxylase, and phenylalanine hydroxylase) and nitric oxide synthase. However, some HPD/DRD cases have not exhibited any abnormalities in their genetic backgrounds.1 The symptoms of HPD/DRD are thought to be caused by the dysfunction of nigrostriatal dopaminergic neurons, leading to symptoms resembling those of Parkinson disease.5 A BH4 deficiency can cause the diminished production of dopamine and serotonin, resulting in the symptoms of dopamine and serotonin deficiencies. The depletion of serotonin causes a brain development such as synaptogenesis. Consequently, disorders of learning such as autism and mental retardation occur.6 In fact, the plasma serotonin level in this patient was low, compared with that in healthy controls. However, previous reports have not yet revealed that HPD/DRD can be accompanied by mental retardation. This case report is the first mention of a case with HPD/DRD and mental retardation. The possibility of HPD/DRD-like patient should be considered and CSF neopterin levels measured, when a patient with mental retardation and juvenile Parkinson disease-like symptoms is encountered.