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ObjectiveRiboflavin transporter deficiencies (RTDs), involving SLC52A3and SLC52A2genes, 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 SLC52A2patients). 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.

IMPORTANCE Mutations in the SQSTM1 gene, coding for p62, are a cause of Paget disease of bone and amyotrophic lateral sclerosis (ALS). Recently, SQSTM1 mutations were confirmed in ALS, and mutations were also identified in 3 patients with frontotemporal dementia (FTD), suggesting a role for SQSTM1 in FTD. OBJECTIVE To evaluate the exact contribution of SQSTM1 to FTD and FTD with ALS (FTD-ALS) in an independent cohort of patients. DESIGN A SQSTM1 mutation was first identified in a multiplex family with FTD by use of whole-exome sequencing. To evaluate the frequency of SQSTM1 mutations, we sequenced this gene in a cohort of patients with FTD or FTD-ALS, with no mutations in known FTD and ALS genes. SETTING Primary care or referral center. PARTICIPANTS An overall cohort of 188 French patients, including 132 probands with FTD and 56 probands with FTD-ALS. MAIN OUTCOMES AND MEASURES Frequency of SQSTM1 mutations in patients with FTD or FTD-ALS; description of associated phenotypes. RESULTS We identified 4 heterozygous missense mutations in 4 unrelated families with FTD; only 1 family had clinical symptoms of Paget disease of bone, and only 1 family had clinical symptoms of FTD-ALS, possibly owing to the low penetrance of some of the clinical manifestations. CONCLUSIONS AND RELEVANCE Although the frequency of the mutations is low in our series (4 of 188 patients [2%]), our results, similar to those already reported, support a direct pathogenic role of p62 in different types of FTD.

BACKGROUND Serine synthesis defects, characterized by developmental delay and seizures, have been described in children. OBJECTIVE To describe a case of serine synthesis defect due to 3-phosphoglycerate dehydrogenase deficiency in an adult with prominent chronic polyneuropathy. DESIGN Case report. SETTING Neurologic referral center. PATIENT A 31-year-old man with congenital cataracts, mild psychomotor retardation, slight cerebellar ataxia, and chronic axonal sensorimotor polyneuropathy. INTERVENTIONS Electrophysiologic, metabolic, and genetic testing and treatment with oral L-serine. MAIN OUTCOME MEASURES Serine values in plasma and cerebrospinal fluid and clinical examination. RESULTS Amino acid analysis showed low serine levels in plasma and cerebrospinal fluid, and genetic analysis revealed 2 heterozygous mutations in the PGDH gene. Treatment with high-dose serine resulted in normalization of plasma serine values and subjective functional improvement. CONCLUSIONS This case expands the phenotypic spectrum of 3-phosphoglycerate dehydrogenase deficiency. Plasma amino acid chromatography should be added to the list of investigations performed in patients with Charcot-Marie-Tooth–like polyneuropathy, especially if it is associated with psychomotor delay and congenital cataracts.

L’analyse de la littérature indique que près de 10 % des patients adressés à des centres de références de pathologie du motoneurone pour suspicion de sclérose latérale amyotrophique (SLA) vont présenter un diagnostic différentiel. Une grande majorité d’entre eux se situe dans le champ de neuropathies périphériques motrices. Ceci traduit bien la difficulté devant un tel tableau de discriminer la SLA d’autres neuropathies motrices périphériques qu’elles soient de cause hérédo-dégénérative, mécanique, toxique, infectieuse ou inflammatoire, certaines de ces pathologies étant marquées par un profil évolutif plus bénin que la SLA voire accessible à un traitement curatif. Sans chercher à dresser un catalogue exhaustif des causes de neuropathie à expression motrice le but de cet exposé sera d’établir quelques bases du raisonnement clinique et neurophysiologique visant à localiser un déficit moteur au niveau du neurone ou du nerf moteur et d’en appréhender la cause à partir de questionnements élémentaires portant sur la présentation et la répartition du trouble moteur, son site de début, son mode évolutif ou en fonction d’éventuelles manifestations associées.