Sensory Ataxia Research Articles

The New Entity of Paranodopathies: A Target Structure with Therapeutic Consequences

AbstractAutoimmune neuropathies with autoantibodies against paranodal proteins have been described in the last few years. They comprise a subgroup of inflammatory neuropathies with IgG4 autoantibodies against the paranodal proteins neurofascin-155, contactin-1 and caspr-1. Although this subtype of autoimmune neuropathy represents less than 10% of all patients diagnosed with CIDP, it is of high interest as they show a different response to treatment. Even though there are no therapeutic studies available due to the limited number of patients identified so far, all case reports published so far report an excellent response to treatment with rituximab, and in most cases no response to treatment with IVIG, the standard therapy of CIDP. The typical clinical picture of patients with autoantibodies against paranodal proteins is characterized by an acute onset of a severe predominantly motor neuropathy, often accompanied by action tremor and sensory ataxia, with demyelinating features in the nerve conduction studies but an axonal histological phenotype. The latter may be explained by the pathogenetic concept of a paranodopathy/nodopathy, a disease of the paranode/node of Ranvier.

Association of Helicobacter pylori infection with megaloblastic anemia: a single centre experience

Background: Histopathological changes due to Helicobacter pylori infection are well characterized but clinical and pathological outcome resulting from the infection are incompletely described and many studies are available from western countries but few data are available from Indian population. Objective: The study has been conducted to observe whether H. pylori infection is associated with gastric atrophy leading to the development of megaloblastic anemia. Material and methods: It was a cross-sectional study with one year duration. Total 30 patients who were suspected to have megaloblastic anemia underwent upper endoscopy, with simultaneous test by Urease test to screen for H. pylori infection. Biopsies were taken, one from antrum and body and another from fundus. These biopsies were studied for H. pylori infection, as well as the level of gastritis and gastric atrophy. Statistical analysis was done by using percentage proportion. Result: Out of 30 patients, 25 were male and 5 were female. Mean age of the study was 33.03±5.85 years. Age group 51–60 years had maximum i.e. 30% of patients. Out of 30 patients, 17 patients had knuckle pigmentation, 7 patients had gray hair, 2 patients had sensory ataxia and 4 patients had normal clinical findings. All the patients of the study had macrocytosis on peripheral smear. Six patients had thrombocytopenia and 5 patients had hypersegmented neutrophils. Out of 30 patients, 10, 2, and 4 patients had mild, moderate, and severe gastritis, respectively on histopathological examination. Five patients had chronic gastritis and 3 had superficial gastritis. Four patients had normal biopsy and 2 patients had pure atrophy. Only one patient came positive for H. pylorus and rest 29 patients were negative for H. pylori. Conclusion: Incidence of H. pylori in the study population of 30 megaloblastic patients was found to be 3%. H. pylori are not associated with gastric atrophy.

HEMATOLOGIC MANIFESTATIONS OF CROHN'S DISEASE: TWO CLINICAL CASES

Inflammatory bowel diseases (IBD) are commonly associated with extraintestinal manifestations, hematological disorders being the most special among them. In some cases, they dominate the clinical picture masking the intestinal manifestations of the underlying disease. Aplastic anemia is an extremely rare extraintestinal IBD manifestation. There are only two clinical cases of aplastic anemia associated with ulcerative colitis and non with Crohn's disease reported in the literature. Combination of Crohn's disease and В₁₂-deficient anemia is more prevalent, but is seen usually only after more than 20 cm of the ileus has been resected. The first clinical case presented in this paper is a combination of severe fistula-forming Crohn's disease with a constriction in the terminal part of the ileus and profound pancytopenia as an outcome of aplastic anemia. This profound pancytopenia is associated with an extremely high risk of life-threatening complications both of surgical treatment, as well as of several chemotherapeutic agents, which made the management of this patient difficult. The second clinical case demonstrates the manifestation of Crohn's disease as ileocolitis starting from the symptoms of cobalamin deficiency: severe В₁₂-deficient anemia, funicular myelosis and sensory ataxia, with blunted intestinal symptoms. This made the initial diagnosis and timely treatment difficult. Replacement therapy with cobalamin injections and treatment with glucocorticoids and antibacterials led to endoscopically confirmed remission of Crohn's disease and normalization of hematological parameters, with persistent polyneuropathy. Thus, management of patients with Crohn's disease should be multidisciplinary. In the case of anemia, leucopenia and/or thrombocytopenia in IBD patients it is necessary to exclude potential myelodysplasia and bone marrow aplasia. In the event of megaloblastic anemia and/or progressive polyneuropathy one should bear in mind potential cobalamin deficiency. However, in severe anemia it is important to perform diagnostic assessment for IBD, first of all, for Crohn's disease, especially, if any intestinal symptoms are present.

A Case Report of Nonvasculitic Autoimmune Inflammatory Meningoencephalitis with Sensory Ganglionopathy: A Rare Presentation of Sjögren Syndrome

A 68-year-old Caucasian female was admitted to the emergency department with a progressive history of behavioural symptoms and anxiety followed by visual and auditory hallucinations, forgetfulness, and impaired gait in the previous 3 months. On examination she was psychotic and had a postural and rest tremor of the upper limbs, cogwheel rigidity of the four limbs, retropulsion on standing position, and inability to walk. During the following 2 weeks she developed xerostomia and unilateral parotiditis that improved with steroids. A simultaneous improvement of the cognitive abilities allowed for the detection of sensory ataxia of the lower limbs. Sensory ganglionopathy was then detected with electrophysiological studies. A diagnosis of Sjögren syndrome was suspected and confirmed by salivary gland scintigraphy, Schirmer's test, and submaxillary gland biopsy. We report a case of Sjögren syndrome associated with central and peripheral nervous system involvement, without sicca symptoms preceding the neurological clinical picture. The coexistence of ganglionopathy and a favourable response to immunosuppression are key features that can lead to the correct diagnosis in cases with atypical CNS symptoms, mimicking a rapidly progressive dementia.

Pathophysiology of Ataxia in Fisher Syndrome

Fisher syndrome is regarded as a peculiar inflammatory neuropathy associated with ophthalmoplegia, ataxia, and areflexia. The disorder is associated with preceding infection, cerebrospinal fluid albumino-cytological dissociation, and spontaneous recovery, and regarded as a variant of Guillain-Barré syndrome. The discovery of anti-GQ1b IgG antibodies led to dramatic advances in understanding the pathophysiology of Fisher syndrome. The lesions in Fisher syndrome are determined by expression of ganglioside GQ1b in the human nervous system. This review article focuses on the pathophysiology of ataxia in Fisher syndrome. Current evidence suggests that antibody attack on Group Ia neurons in the dorsal root ganglia is mainly responsible for the sensory ataxia. Involvement of the muscle spindles might also contribute to the development of ataxia.

Unusual presentation Of Sjögren-associated neuropathy with plasma cell-rich infiltrate.

Sjögren syndrome is thought to be a lymphocyte-driven process. Peripheral nervous system involvement occurs in about 20%-25% of patients. A sensory-predominant, large-fiber peripheral neuropathy is most common, and it is usually associated with a subacute to chronic presentation. We report a rare case of an acute Sjögren-associated, sensory predominant, length-dependent peripheral neuropathy mimicking Guillain-Barré syndrome. The patient presented with sensory ataxia preceded by fever and polyarthralgia. She gave a history of years of dry eyes and dry mouth. She had a positive Shirmer test, abnormal salivary gland scan, and positive SS-A and SS-B antibodies. A sural nerve biopsy showed an unusual, dense, non-IgG4, polyclonal, plasma-cell perivascular infiltrate. The patient responded to treatment with weekly pulse intravenous methylprednisolone. Sjögren syndrome can present with acute-onset, sensory predominant peripheral neuropathy. The role of plasma cells in Sjögren syndrome is unexplored and deserves further study. Muscle Nerve 55: 605-608, 2017.

POLG2 deficiency causes adult-onset syndromic sensory neuropathy, ataxia and parkinsonism.

ObjectiveMitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative disorders such as ataxia and Parkinson's disease. We describe an extended Belgian pedigree where seven individuals presented with adult‐onset cerebellar ataxia, axonal peripheral ataxic neuropathy, and tremor, in variable combination with parkinsonism, seizures, cognitive decline, and ophthalmoplegia. We sought to identify the underlying molecular etiology and characterize the mitochondrial pathophysiology of this neurological syndrome.MethodsClinical, neurophysiological, and neuroradiological evaluations were conducted. Patient muscle and cultured fibroblasts underwent extensive analyses to assess mitochondrial function. Genetic studies including genome‐wide sequencing were conducted.ResultsHallmarks of mitochondrial dysfunction were present in patients’ tissues including ultrastructural anomalies of mitochondria, mosaic cytochrome c oxidase deficiency, and multiple mtDNA deletions. We identified a splice acceptor variant in POLG2, c.970‐1G>C, segregating with disease in this family and associated with a concomitant decrease in levels of POLG2 protein in patient cells.InterpretationThis work extends the clinical spectrum of POLG2 deficiency to include an overwhelming, adult‐onset neurological syndrome that includes cerebellar syndrome, peripheral neuropathy, tremor, and parkinsonism. We therefore suggest to include POLG2 sequencing in the evaluation of ataxia and sensory neuropathy in adults, especially when it is accompanied by tremor or parkinsonism with white matter disease. The demonstration that deletions of mtDNA resulting from autosomal‐dominant POLG2 variant lead to a monogenic neurodegenerative multicomponent syndrome provides further evidence for a major role of mitochondrial dysfunction in the pathomechanism of nonsyndromic forms of the component neurodegenerative disorders.

Posterior Spinal Artery Infarction Presenting as a Sensory Ataxia

Posterior Spinal Artery Infarction Presenting as a Sensory Ataxia

Gait disorders in adults and the elderly : Aclinical guide.

SummaryHuman gait depends on a complex interplay of major parts of the nervous, musculoskeletal and cardiorespiratory systems. The individual gait pattern is influenced by age, personality, mood and sociocultural factors. The preferred walking speed in older adults is a sensitive marker of general health and survival. Safe walking requires intact cognition and executive control. Gait disorders lead to a loss of personal freedom, falls and injuries and result in a marked reduction in the quality of life. Acute onset of a gait disorder may indicate a cerebrovascular or other acute lesion in the nervous system but also systemic diseases or adverse effects of medication, in particular polypharmacy including sedatives. The prevalence of gait disorders increases from 10 % in people aged 60–69 years to more than 60 % in community dwelling subjects aged over 80 years. Sensory ataxia due to polyneuropathy, parkinsonism and frontal gait disorders due to subcortical vascular encephalopathy or disorders associated with dementia are among the most common neurological causes. Hip and knee osteoarthritis are common non-neurological causes of gait disorders. With advancing age the proportion of patients with multiple causes or combinations of neurological and non-neurological gait disorders increases. Thorough clinical observation of gait, taking a focused patient history and physical, neurological and orthopedic examinations are basic steps in the categorization of gait disorders and serve as a guide for ancillary investigations and therapeutic interventions. This clinically oriented review provides an overview on the phenotypic spectrum, work-up and treatment of gait disorders.

P.387 - Riboflavin transporter deficiency diagnosed 30 years after onset of symptoms

Mutations in the riboflavin transporter genes SLC52A2 and SLC52A3 cause a neurodegenerative disorder formerly known as Brown–Vialetto–van Laere (BVVL) syndrome, now renamed to riboflavin transporter deficiency. We present a patient who developed hypotonia, respiratory problems and feeding problems at the age of 8 months. His respiratory problems necessitated mechanical ventilation for 8 months. During follow up global developmental delay, bilateral sensorineural deafness and profound sensory ataxia were diagnosed. Extensive additional investigations (MRI, EMG, metabolic workup, CSF analysis and muscle biopsy) in infancy did not reveal any abnormalities apart from raised ethylmalonic acid. As a mitochondrial disorder was suspected he was treated with thiamine, riboflavin, biotin and carnitine. In the ensuing years these supplements were discontinued twice. Each time parents noticed worsening of his clinical condition. A second muscle biopsy performed at the age of 15 years showed central cores. Sequencing of RYR1 gene revealed one missense mutation, which was also present in the asymptomatic mother. Whole exome sequencing performed at the age of 30 years revealed a homozygous mutation in SLC52A3 gene (c.1128C > G(p.(Tyr376*)), which led to the diagnosis of Brown–Vialetto–van Laere syndrome. Riboflavin transporter deficiencies formerly known as Brown–Vialetto–van Laere syndrome present with cranial nerve deficits including hearing loss, weakness, sensory symptoms including sensory ataxia, feeding difficulties and respiratory difficulties which are caused by a progressive axonal sensory and motor peripheral neuropathy and a cranial neuropathy. Diagnosis can only be made through molecular analysis of all genes. Treatment with oral supplementation of riboflavin is lifesaving.

A novel path to chronic proprioceptive disability with oxaliplatin: Distortion of sensory encoding

Persistent neurotoxic side effects of oxaliplatin (OX) chemotherapy, including sensory ataxia, limit the efficacy of treatment and significantly diminish patient quality of life. The common explanation for neurotoxicity is neuropathy, however the degree of neuropathy varies greatly among patients and appears insufficient in some cases to fully account for disability. We recently identified an additional mechanism that might contribute to sensory ataxia following OX treatment. In the present study, we tested whether that mechanism, selective modification of sensory signaling by muscle proprioceptors might result in behavioral deficits in rats. OX was administered once per week for seven weeks (cumulative dose i.p. 70mg/kg) to adult female Wistar rats. Throughout and for three weeks following treatment, behavioral analysis was performed daily on OX and sham control rats. Compared to controls, OX rats demonstrated errors in placing their hind feet securely and/or correctly during a horizontal ladder rung task. These behavioral deficits occurred together with modification of proprioceptor signaling that eliminated sensory encoding of static muscle position while having little effect on encoding of dynamic changes in muscle length. Selective inability to sustain repetitive firing in response to static muscle stretch led us to hypothesize that OX treatment impairs specific ionic currents, possibly the persistent inward Na currents (NaPIC) that are known to support repetitive firing during static stimulation in several neuron types, including the class of large diameter dorsal root ganglion cells that includes muscle proprioceptors. We tested this hypothesis by determining whether the chronic effects of OX on the firing behavior of muscle proprioceptors in vivo were mimicked by acute injection of NaPIC antagonists. Both riluzole and phenytoin, each having multiple drug actions but having only antagonist action on NaPIC in common, reproduced selective modification of proprioceptor signaling observed in OX rats. Taken together, these findings lead us to propose that OX chemotherapy contributes to movement disability by modifying sensory encoding, possibly via a chronic neurotoxic effect on NaPIC in the sensory terminals of muscle proprioceptors.

Can vitamin B12 deficiency manifest with acute posterolateral or posterior cord syndrome?

Vitamin B12 deficiency can cause varied neurological manifestations which are subacute to chronic in onset. Subacute combined degeneration of spinal cord is one such characteristic neurological manifestation of vitamin B12 deficiency. We report a case series of five patients who presented with acute onset (<15 days) neurological manifestations due to vitamin B12 deficiency. Detailed history and clinical examination along with appropriate relevant investigations were done in all patients. Out of the five, two cases were of useless hand syndrome due to involvement of posterior column of the cervical spinal cord, another two patients presented with acute posterolateral cord syndrome causing gait ataxia and one acute posterior cord syndrome presented with acute sensory gait ataxia. Laboratory investigations were compatible with the diagnosis of cobalamin deficiency in all cases. All cases improved after parenteral vitamin B12 supplementation. Vitamin B12 deficiency can present with acute neurological manifestations.

Arsenic poisoning and Mees' lines.

A 40-year-old male presented with 4 weeks’ history of numbness with painful paraesthesias in limbs. The paraesthesias (tingling and gnawing pain) and numbness started distally in hands and feet, almost simultaneously, and reached up till wrists and mid legs over 2 weeks. At this time, he noticed imbalance on walking which worsened in dark and some difficulty in gripping objects Examination revealed mild hand grip weakness, generalized areflexia, pansensory loss in glove and stocking distribution and sensory ataxia. He had antecedent fever, loose stools, transaminitis, right pleural effusion 2 weeks before the …

P.039 New association of anti-Hu positive limbic encephalitis and sensory ganglionopathy with small cell gastric tumour

Background: While anti-Hu antibody associated encephalitis has been well-documented in association with a variety of neoplastic processes, paraneoplastic limbic encephalitis and sensory ganglionopathy with positive anti-Hu antibodies has not previously been linked in the literature with a neuroendocrine gastric tumour of advanced stage. Methods: Case report Results: We present the case of an 86-year old woman who developed behavioural changes, paroxysmal anxiety attacks and poor balance several months after being diagnosed with poorly differentiated gastric small cell tumour in a clinical setting of weight loss and anemia. Anti-Hu antibodies were present. MRI showed signal abnormalities in the right mesial temporal lobe with contrast enhancement. Paroxysmal lateralized EEG changes were recorded and EMG/NCS showed absent sensory nerve responses. Behavioural symptoms stabilized under treatment with intravenous immunoglobulins, but sensory ataxia continued to worsen. The patient declined further therapy and deceased two months after transfer to palliative care. Conclusions: To our knowledge, this is the first report linking small cell gastric tumour with limbic encephalitis, sensory ganglionopathy-associated ataxia and anti-Hu antibodies. This description further broadens the clinical spectrum of anti-Hu syndrome.

Genotype–phenotype correlation of Charcot-Marie-Tooth type 1E patients with PMP22 mutations

Charcot-Marie-Tooth disease type 1E (CMT1E) is a demyelinating motor and sensory neuropathy with peripheral myelin protein 22 (PMP22) point mutations. The objective of this study was to identify genetic causes and determine genotype–phenotype correlation in two Korean demyelinating CMT patients based on whole exome sequencing (WES), histological examination of distal sural nerve, and magnetic resonance imaging (MRI) of leg. WES revealed two de novo PMP22 mutations in the two demyelinating CMT patients, including one novel p.Leu82Pro (c.245T>A) mutation in one patient and one previously reported p.Ser72Leu (c.215C>T) mutation in the other patient. Both mutation sites were located in the well conserved second transmembrane domain. No control had the same mutations. The affected individual with the novel p.Leu82Pro mutation showed early onset, scoliosis, and sensory ataxia with ability to walk without assistance. Histopathological examination showed severe damage of myelin and axons. No compound muscle action potentials (CMAPs) were evoked in the upper or lower limb nerves. Leg MRIs revealed mild fatty infiltration of the bilateral peronei muscles consistent with clinical manifestations. The patient with the p.Ser72Leu mutation showed developmental delay in infancy. No CMAPs were elicited. However, she was also able to walk without assistance. In spite of markedly severe electrophysiological defects, leg MRIs showed almost normal findings except slight muscle atrophies of the lower legs. Both patients presented similar clinical features including no CMAPs in electrophysiological tests and mild fatty replacement in the lower leg MRI. Therefore, there was a good genotype–phenotype correlation in both cases.

54. Prevention of Sensory Ataxia in a Novel Mouse Model of Friedreich Ataxia Using Gene Therapy Approach

Friedreich's ataxia (FRDA), the most common autosomal recessive ataxia, is characterized by a sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy and increase incidence of diabetes. FRDA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Impaired mitochondrial oxidative phosphorylation, bioenergetics imbalance, deficit of Fe-S cluster enzymes and mitochondrial iron overload occur in individuals with FRDA. Proprioceptive neurons within the dorsal root ganglia (DRG) and cardiomyocytes are the most affected tissues in FRDA patients. To date there are not effective treatment for FRDA. We have previously established the primary proof-of-concept for developing gene therapy of FRDA cardiomyopathy and showed that adeno-associated virus (AAV) rh. 10 vector expressing human FXN injected intravenously not only prevented the onset of the cardiac disease in a faithful FRDA cardiac mouse model, but also, when administered at the time of heart failure, rapidly and completely reversed the cardiac disease. To date, there were unfortunately no adequate neuronal mouse model to address the possibility of gene therapy for the neuronal aspects of FRDA. We therefore recently generated a novel mouse model that recapitulates faithfully the sensory ataxia associated to FRDA using the conditional approach to delete frataxin specifically in the proprioceptive neurons of the DRG. By behavioural analysis, the mice exhibit an ataxic phenotype beginning at 3 weeks of age, which is rapidly progressive. Electrophysiological studies reveal a significant decrease of sensory wave already at 4.5 weeks and almost a complete loss at 8 weeks of age. A significant loss of sensory neurons within dorsal root ganglia is observed at 17.5 weeks of age compare to age matched controls. Ultrastructural analysis of sciatic and saphenous nerves showed abnormalities at early time points. Using this mouse model, we have developed an AAV gene therapy approach based on an intravenous delivery of AAV9-CAG-hFXN-HA vector at an early symptomatic stage of the disease. Mice displayed a complete prevention of the ataxic phenotype and electrophysiological analysis showed maintenance of the sensory wave in the treated animals. Histological studies revealed a complete prevention of neuronal loss in the DRG as well as a normal ultrastructure of saphenous and sciatic nerve. As results are encouraging, we plan to evaluate the potential therapeutical effect at a more advanced stage of the disease.

The difficulties with vitamin B12

A 22-year-old woman presented with progressive sensory ataxia and optic neuropathy. Previous investigation by her general practitioner had found a low serum vitamin B12, which had been corrected with oral...

Clinical presentation and outcome of riboflavin transporter deficiency: mini review after five years of experience.

IntroductionRiboflavin (vitamin B2) is absorbed in the small intestine by the human riboflavin transporters RFVT1 and RFVT3. A third riboflavin transporter (RFVT2) is expressed in the brain. In 2010 it was demonstrated that mutations in the riboflavin transporter genes SLC52A2 (coding for RFVT2) and SLC52A3 (coding for RFVT3) cause a neurodegenerative disorder formerly known as Brown-Vialetto-Van Laere (BVVL) syndrome, now renamed to riboflavin transporter deficiency. Five years after the diagnosis of the first patient we performed a review of the literature to study the presentation, treatment and outcome of patients with a molecularly confirmed diagnosis of a riboflavin transporter deficiency.MethodA search was performed in Medline, Pubmed using the search terms ‘Brown-Vialetto-Van Laere syndrome’ and ‘riboflavin transporter’ and articles were screened for case reports of patients with a molecular diagnosis of a riboflavin transporter deficiency.ResultsReports on a total of 70 patients with a molecular diagnosis of a RFVT2 or RTVT3 deficiency were retrieved. The riboflavin transporter deficiencies present with weakness, cranial nerve deficits including hearing loss, sensory symptoms including sensory ataxia, feeding difficulties and respiratory difficulties which are caused by a sensorimotor axonal neuropathy and cranial neuropathy. Biochemical abnormalities may be absent and the diagnosis can only be made or rejected by molecular analysis of all genes. Treatment with oral supplementation of riboflavin is lifesaving. Therefore, if a riboflavin transporter deficiency is suspected, treatment must be started immediately without first awaiting the results of molecular diagnostics.

31. Sensory peripheral neuropathy in a novel mutation of FLVCR1

Posterior Column Ataxia and Retinitis Pigmentosa (PCARP) is an autosomal-recessive neurodegenerative syndrome. Standard phenotype expected: areflexia and retinitis pigmentosa in infancy; night blindness and peripheral visual field loss in late childhood; evaluation to sensory ataxia secondary to degeneration of the posterior columns of the spinal cord. We reported a case of 3 yrs old children with PCARP secondary to FLVCR1 mutation and atypical phenotype. Our patient have a congenital and progressive acro-osteolysis of fingers and precocious ataxia with general hypotonia, and deep tendon reflex absent in the legs. No visual impairment was reported and the fundus oculi was normal. ERG was normal. Nerve conduction study showed sensory peripheral neuropathy. Median-nerve SEPs were not recordable for sensitive neuropathy. Brain and total spinal cord MRI was normal. Genetic study showed a truncated FLVCR1 protein by mother and new potentially pathogenetic mutation by father. Sensory peripheral neuropathy was reported in only few cases of PCARP.

DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies.