Late-onset riboflavin transporter deficiency: a treatable mimic of various motor neuropathy aetiologies

2020 ◽  
Vol 92 (1) ◽  
pp. 27-35
Author(s):  
Christophe Carreau ◽  
Charline Benoit ◽  
Guido Ahle ◽  
Cécile Cauquil ◽  
Agathe Roubertie ◽  
...  
Keyword(s):  
Late Onset ◽  
High Dose ◽  
Motor Neuropathy ◽  
Biochemical Tests ◽  
Oral Supplementation ◽  
Clinical Presentations ◽  
Hereditary Motor Neuropathy ◽  
Transporter Deficiency ◽  
Per Oral ◽  
Lateral Sclerosis

ObjectiveRiboflavin transporter deficiencies (RTDs), involving SLC52A3 and SLC52A2 genes, have recently been related to Brown-Vialetto-Van Laere (BVVL) syndrome, a hereditary paediatric condition associating motor neuropathy (MN) and deafness. BVVL/RTD has rarely been reported in adult patients, but is probably underdiagnosed due to poor knowledge and lack of awareness of this form of disease among neurologists. In this study, we aimed to investigate the phenotype and prognosis of RTD patients with late-onset MN.MethodsWe retrospectively collected clinical, biological and electrophysiological data from all French RTD patients with MN onset after 10 years of age (n=6) and extracted data from 19 other similar RTD patients from the literature.ResultsAdult RTD patients with MN had heterogeneous clinical presentations, potentially mimicking amyotrophic lateral sclerosis or distal hereditary motor neuropathy (56%), multinevritis with cranial nerve involvement (16%), Guillain-Barré syndrome (8%) and mixed motor and sensory neuronopathy syndromes (20%, only in SLC52A2 patients). Deafness was often diagnosed before MN (in 44%), but in some patients, onset began only with MN (16%). The pattern of weakness varied widely, and the classic pontobulbar palsy described in BVVL was not constant. Biochemical tests were often normal. The majority of patients improved under riboflavin supplementation (86%).InterpretationWhereas late-onset RTD may mimic different acquired or genetic causes of motor neuropathies, it is a diagnosis not to be missed since high-dose riboflavin per oral supplementation is often highly efficient.

Characterising the phenotype and mode of inheritance of patients with inherited peripheral neuropathies carrying MME mutations

2018 ◽  
Vol 55 (12) ◽  
pp. 814-823 ◽  
Author(s):  
Vincenzo Lupo ◽  
Marina Frasquet ◽  
Ana Sánchez-Monteagudo ◽  
Ana Lara Pelayo-Negro ◽  
Tania García-Sobrino ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Late Onset ◽  
Axonal Neuropathy ◽  
Genetic Diagnosis ◽  
Hereditary Neuropathy ◽  
Motor Neuropathy ◽  
Charcot Marie Tooth Disease ◽  
Hereditary Motor Neuropathy ◽  
Index Cases ◽  
Mode Of Inheritance

BackgroundMutations in the metalloendopeptidase (MME) gene were initially identified as a cause of autosomal recessive Charcot-Marie-Tooth disease type 2 (CMT2). Subsequently, variants in MME were linked to other late-onset autosomal dominant polyneuropathies. Thus, our goal was to define the phenotype and mode of inheritance of patients carrying changes in MME.MethodsWe screened 197 index cases with a hereditary neuropathy of the CMT type or distal hereditary motor neuropathy (dHMN) and 10 probands with familial amyotrophic lateral sclerosis (fALS) using a custom panel of 119 genes. In addition to the index case subjects, we also studied other clinically and/or genetically affected and unaffected family members.ResultsWe found 17 variants in MME in a total of 20 index cases, with biallelic MME mutations detected in 13 cases from nine families (three in homozygosis and six in compound heterozygosis) and heterozygous variants found in 11 families. All patients with biallelic variants had a similar phenotype, consistent with late-onset axonal neuropathy. Conversely, the phenotype of patients carrying heterozygous mutations was highly variable [CMT type 1 (CMT1), CMT2, dHMN and fALS] and mutations did not segregate with the disease.ConclusionMME mutations that segregate in an autosomal recessive pattern are associated with a late-onset CMT2 phenotype, yet we could not demonstrate that MME variants in heterozygosis cause neuropathy. Our data highlight the importance of establishing an accurate genetic diagnosis in patients carrying MME mutations, especially with a view to genetic counselling.

scholarly journals Late onset distal hereditary motor neuropathy type IIB (dHMN IIB) – case reports

2018 ◽  
Vol 18 (3) ◽  
pp. 144-147
Author(s):  
Mateusz Spławski ◽  
◽  
Katarzyna Broniarek ◽  
Robert Bonek ◽  
◽  
...  
Keyword(s):  
Late Onset ◽  
Case Reports ◽  
Motor Neuropathy ◽  
Hereditary Motor ◽  
Hereditary Motor Neuropathy

scholarly journals P.057 Distal hereditary motor neuropathy type I due to the GARS: c.1415A>G, p.His472Arg mutation

2016 ◽  
Vol 43 (S2) ◽  
pp. S34-S34
Author(s):  
AG Florendo-Cumbermack ◽  
K Kimpinski ◽  
S Venance
Keyword(s):  
Genetic Characterization ◽  
Case Reports ◽  
Treatment Options ◽  
Type I ◽  
Motor Neuropathy ◽  
Juvenile Onset ◽  
Hereditary Motor ◽  
Clinical Presentations ◽  
Hereditary Motor Neuropathy ◽  
Exon 11

Background: The distal hereditary motor neuropathies (dHMN) have been characterized through case reports and family studies. Their genetic characterization remains a work in progress. An appreciation of the genetic underpinnings may lead to treatment options in the future. Hence reports, like this one, which add to this understanding, remain extremely important. Methods: The clinical presentations, electrophysiology and genetics of two patients with the dHMN I phenotype are described. Results: A mother and son presented with slowly progressive distal weakness of the lower extremities with onset in the first and second decades. Distal weakness of the upper extremities developed later. Examination 20 and 50 years after onset revealed wasting and weakness of distal upper and lower extremity muscles with absent distal and preserved proximal deep tendon reflexes. Sensory examination was normal. Electrodiagnostic studies demonstrated a motor axonopathy. Genetics testing revealed a missense mutation on chromosome 7, exon 11 of the GARS gene: c.1415A>G (p.His472Arg). Conclusions: GARS mutations have been identified in patients with the dHMN I (juvenile onset distal weakness and wasting) and dHMN V (upper limb predominant) phenotypes. However, this mutation has not previously been directly linked to the dHMN I phenotype.

Liver Histological Improvement After Administration of High-Dose Vitamin C in Guinea Pig with Nonalcoholic Steatohepatitis

2018 ◽  
Vol 88 (5-6) ◽  
pp. 263-269
Author(s):  
Seong-Hoon Park ◽  
A Lum Han ◽  
Na-Hyung Kim ◽  
Sae-Ron Shin
Keyword(s):  
Liver Biopsy ◽  
Vitamin C ◽  
Nonalcoholic Steatohepatitis ◽  
Guinea Pigs ◽  
Normal Diet ◽  
High Dose ◽  
Biochemical Tests ◽  
Deficient Diet ◽  
Histological Improvement ◽  
Vit C

Abstract. Background: Vitamin C is a strong antioxidant, and the health effects of vitamin C megadoses have not been validated despite the apparent health benefits. Therefore, the present study sought to confirm the effects of vitamin C megadoses. Materials and Methods : Four groups of six guinea pigs were used. Each group was fed one of the following diets for three weeks: normal diet, methionine choline-deficient diet, methionine choline-deficient diet + vitamin C megadose (MCD + vit C 2.5 g/kg/day), and methionine-choline deficient diet + ursodeoxycholic acid (MCD + UDCA 30 mg/kg/day). The MCD diet was given to induce nonalcoholic steatohepatitis, and UDCA was used to treat nonalcoholic steatohepatitis. Three weeks after initial diet administration, the results of biochemical tests and liver biopsy were compared between the groups. Results: The cytoplasm state was similar in the MCD + vit C and MCD + UDCA groups, exhibiting clearing of the cytoplasm and ballooning degeneration. However, macrovesicular steatosis was not observed in the MCD + vit C group. Aspartate transaminase and alanine transaminase were elevated significantly following vitamin C administration. Conclusions: The present study confirmed that alone vitamin C megadoses are potential remedies for nonalcoholic steatohepatitis, based on the liver biopsy results of guinea pigs that were unable to synthesize vitamin C.

Neurofilament Proteins as Prognostic Biomarkers in Neurological Disorders

2020 ◽  
Vol 25 (43) ◽  
pp. 4560-4569 ◽  
Author(s):  
Yichen Lee ◽  
Bo H. Lee ◽  
William Yip ◽  
Pingchen Chou ◽  
Bak-Sau Yip
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Nervous System ◽  
Trinucleotide Repeat ◽  
Muscular Atrophy ◽  
Electric Signal ◽  
Motor Neuropathy ◽  
Post Translational Modification ◽  
Neurofilament Proteins ◽  
Type Iv ◽  
Lateral Sclerosis

Neurofilaments: light, medium, and heavy (abbreviated as NF-L, NF-M, and NF-H, respectively), which belong to Type IV intermediate filament family (IF), are neuron-specific cytoskeletal components. Neurofilaments are axonal structural components and integral components of synapses, which are important for neuronal electric signal transmissions along the axons and post-translational modification. Abnormal assembly of neurofilaments is found in several human neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), infantile spinal muscular atrophy (SMA), and hereditary sensory-motor neuropathy (HSMN). In addition, those pathological neurofilament accumulations are known in α-synuclein in Parkinson’s disease (PD), Aβ and tau in Alzheimer’s disease (AD), polyglutamine in CAG trinucleotide repeat disorders, superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP43), neuronal FUS proteins, optineurin (OPTN), ubiquilin 2 (UBQLN2), and dipeptide repeat protein (DRP) in amyotrophic lateral sclerosis (ALS). When axon damage occurs in central nervous disorders, neurofilament proteins are released and delivered into cerebrospinal fluid (CSF), which are then circulated into blood. New quantitative analyses and assay techniques are well-developed for the detection of neurofilament proteins, particularly NF-L and the phosphorylated NF-H (pNF-H) in CSF and serum. This review discusses the potential of using peripheral blood NF quantities and evaluating the severity of damage in the nervous system. Intermediate filaments could be promising biomarkers for evaluating disease progression in different nervous system disorders.

scholarly journals Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hai-Lin Dong ◽  
Jia-Qi Li ◽  
Gong-Lu Liu ◽  
Hao Yu ◽  
Zhi-Ying Wu
Keyword(s):  
Ex Vivo ◽  
Protein Solubility ◽  
Chinese Patients ◽  
Hereditary Neuropathy ◽  
Motor Neuropathy ◽  
Causative Gene ◽  
Hereditary Motor ◽  
Functional Studies ◽  
Hereditary Motor Neuropathy

AbstractSorbitol dehydrogenase gene (SORD) has been identified as a novel causative gene of recessive forms of hereditary neuropathy, including Charcot–Marie–Tooth disease type 2 and distal hereditary motor neuropathy (dHMN). Our findings reveal two novel variants (c.404 A > G and c.908 + 1 G > C) and one known variant (c.757delG) within SORD in four Chinese dHMN families. Ex vivo cDNA polymerase chain reaction confirmed that c.908 + 1 G > C variant was associated with impaired splicing of the SORD transcript. In vitro cell functional studies showed that c.404 A > G variant resulted in aggregate formation of SORD and low protein solubility, confirming the pathogenicity of SORD variants. We have provided more evidence to establish SORD as a causative gene for dHMN.

Distal hereditary motor neuropathy (DHMN): a new locus for an autosomal recessive form

2004 ◽  
Vol 9 (2) ◽  
pp. 122-123 ◽  
Author(s):  
ML Mostacciuolo ◽  
E Crestanello ◽  
F Boaretto ◽  
E Boscolo ◽  
M Liguori ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Motor Neuropathy ◽  
Hereditary Motor ◽  
Autosomal Recessive Form ◽  
Recessive Form ◽  
Hereditary Motor Neuropathy
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