We report a 66-year-old woman who developed
mental deterioration in her school days, and progressive gait disturbance,
dysarthria and
bradykinesia in her 40 s. Her parents were consanguineous, and the two of her brothers were suspected to have the allied disorder. On physical examination, she was short-statured and high-arched palate was observed. Neurological examination revealed
dementia, abnormal eye movement,
dysarthria, spastic paraparesis with
hyperreflexia, bilateral Babinski signs,
cerebellar ataxia and
dysuria. Brain MRI showed marked hypoplasia of corpus callosum with dilatation of lateral ventricles and cerebral sulci and significant cerebellar
atrophy.
Amino acid analyses showed significant elevation of
glycine without
ketosis in serum, cerebrospinal fluid, and urine, which lead us to the diagnosis of late-onset
nonketotic hyperglycinemia(NKH). NKH is known to be a rare autosomal recessive metabolic disorder primarily caused by deficient activity of various components of the mitochondrial
glycine cleavage system. Onset of the disease occurs most often in early infancy, however, later-onset variants have been described. Usually, late-onset NKH only manifests mild
mental deterioration, character change, seizure,
ataxia or
spastic paraparesis, which sometimes makes difficulty in differentiating this disease from other hereditary
cerebellar ataxia or
spastic paraparesis. In addition, many structural brain abnormalities have been reported accompanied with NKH, and especially, agenesis or hypoplasia of corpus callosum is the most characteristic feature in this disease. Therefore, we emphasized that
amino acid analyses should be considered in any patients who have
cerebellar ataxia or
spastic paraparesis of unknown cause with these neuroradiological findings.