[Retinal vasculopathy with cerebral leukoencephalopathy carrying TREX1 mutation diagnosed by the intracranial calcification: a case report].

A 40-year-old woman with renal dysfunction for 2 years was admitted to our hospital suffering from a headache. Family history revealed that her mother had a headache, renal dysfunction, and brain infarction in younger age. She had a retinal hemorrhage, a retinal atrophy, pitting edema in her lower extremities. Her neurological findings were unremarkable. Brain imaging showed multiple white matter lesions accompanied with calcifications and slightly enhancement. Kidney biopsy showed the thrombotic microangiopathy, Gene analysis demonstrated a causative mutation in three-prime repair exonuclease-1 (TREX1) gene, c.703_704insG (p.Val235GlyfsX6), thereby we diagnosed her as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is an autosomal dominant condition caused by C-terminal frame-shift mutation in TREX1. TREX1 protein is a major 3' to 5' DNA exonuclease, which are important in DNA repair. While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. There are no treatments based evidences in RVCL. We administered cilostazol to protect endothelial function, and her brain lesions and renal function have not become worse for 10 months after. It is necessary to consider RVCL associated with TREX1 mutation if a patient has retinal lesions, white matter lesions accompanied with calcifications, and multiple organ dysfunction.

[A case of neurologic muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome with a novel mitochondrial mutation m.8729 G>A].

We report a patient having classical clinical feature of neurologic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and a novel mutation, m.8729 G>A in mitochondria DNA. The patient was referred to our hospital because of progressive ataxia in her limbs and trunk. She had a history of incapability of running long distances from childhood. Neurological examination revealed cerebellar ataxia, distal dominant muscle weakness in the limbs, hyporeflexia, hypoesthesia, myoclonus, sensorineural deafness, and retinitis pigmentosa. Magnetic resonance imaging (MRI) showed atrophy of brain stem and cerebellum as well as calcification of basal ganglia. In both serum and cerebrospinal fluid, lactate and pyruvate levels were elevated. Histological examination of biopsied muscle revealed chronic neurogenic changes without ragged red fibers. Genetic analysis of mitochondrial DNA (mtDNA) of the muscle revealed a heteroplasmic mutation, m.8729 G>A. Chemical analysis of the respiratory chain complexes in her muscle specimen demonstrated lower activities of complexes I and V. In our case, novel mutation of m.8729 G>A in mtDNA was indicated as the cause of NARP syndrome.

[A case of juvenile parkinsonism with expanded SCA8 CTA/CTG repeats].

A 31-year-old man was referred to our hospital because of progressive tremor and clumsiness in his limbs and trunk. His symptoms were started in the right leg then gradually spread to all extremities as well as his trunk for 2 years. Neurological examinations revealed muscle rigidity with resting tremor predominantly right limbs. Akinesia and retropulsion were positive. Neither pyramidal tract sign nor cerebellar ataxia was detected. Genetic testing showed the expansion of SCA8 CTA/CTG repeats as 28/141 repeats. Though moderate expansion (less than 92) of SCA8 repeats has been reported in healthy subjects and patients with various diseases, the extraordinary long expansion of CTA/CTG repeats in SCA8 gene in our patient could be significantly pathological. 600 mg/day of L-DOPA clearly improved his symptoms. Dedicate follow up of the clinical course of our patient and the accumulation of the further cases is essential.