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

Abstract

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.

Cerebral imaging in paediatric mitochondrial disorders

“…99,110,112 Bilateral symmetric calcifications have also been found in a girl with NARP syndrome due to the mutation m.8729G>A resulting in complex-I and complex-IV deficiency. 18 In an infantile male and female sibling with combined complex-I/IV defect, ultrasonography of the brain revealed multifocal cerebral calcifications in one of them. 31 The most common locations of calcifications in MELAS are the caudate nucleus, putamen, globus pallidus, and the thalamus.…”

“…11 In a girl with NARP syndrome due to the mutation m.8729G>A resulting in complex-I and complex-IV deficiency, and onset in childhood, cerebral MRI showed marked atrophy of the cerebellum and the brainstem. 18 In patients carrying mutations in the AIFM1 gene, which encodes a mitochondrial flavoprotein involved in NADH oxidoreductase activity and apoptosis, isolated atrophy of the cerebellar vermis has been reported. 103 Cerebellar ataxia in these patients responded favourably to high-dose riboflavin.…”

“…Calcifications of the cerebral parenchyma or the cerebral arteries have been repeatedly reported in paediatric MIDs. 18 Calcifications may occur uni- or bilaterally and can be most elegantly visualised by CCT. 111 MRI is less apt to visualise cerebral calcifications.…”

“…111 MRI is less apt to visualise cerebral calcifications. Most frequently CNS calcifications have been described in the basal ganglia, 18 and less frequently in the dentate nuclei or the cerebellum. 110 Basal ganglia calcification is not restricted to a particular MID but may occur with most of the known syndromes, most frequently, however, with MELAS and KSS.…”

“…137 In a girl with NARP due to the mutation m.8729G>A, 99 mT-SPECT revealed hypoperfusion of the brainstem and the cerebellum. 18 7.6.4 Cerebral bleeding. Cerebral bleeding has been reported only rarely in paediatric MID patients.…”