Guillaume-Benjamin-Amand Duchenne de Boulogne once remarked that he found neurology "a sprawling infant of unknown parentage, which he succored to lusty youth." He was born in the Boulogne-sur-Mer region of France in1806. He studied medicine in Paris from 1826 to 1831 and later established a practice in Boulogne. In 1835, he observed isolated muscular contractions produced by electropuncture and began investigating the electrical excitation of muscle. In 1842, he left Boulogne for Paris to continue medical research, often visiting hospitals with his electrical equipment to examine unusual cases. He was an inventive investigator who developed several technical innovations, including electrodiagnosis, electrotherapy, needle muscle biopsy, and medical photography. He enumerated his major discoveries in "L'Electrisation Localisee," which included descriptions of progressive muscular atrophy (now called spinal muscular atrophy), atrophic paralysis of childhood (poliomyelitis), progressive locomotor ataxia (tabes dorsalis), glosso-labio-laryngeal paralysis (progressive bulbar palsy), and pseudohypertrophic paralysis (Duchenne muscular dystrophy). Based on Duchenne's intensive investigations, Jean-Martin Charcot refined his medical concepts and established nosological disease entities, calling Duchenne "mon maître en neurologie" (my master in neurology). Duchenne never held a hospital or university position. He died of cerebrovascular disease on September 17, 1875.

Brown-Vialetto-Van Laere syndrome (BVVLS) is an extremely rare genetic neurological disorder caused by riboflavin transport deficiency, an autosomal recessive condition mostly associated with mutations in the SLC52A2 and SLC52A3 genes. It follows a progressive course, typically characterized by sensorineural deafness, facial weakness, ponto-bulbar palsy, ataxia, and peripheral sensory-motor neuropathy. This disease is often associated with childhood mortality if left untreated. We report the case of a 68-year-old woman who first noticed a mild hearing loss at the age of 12. This was followed by a slowly progressive onset of bilateral facial paresis, dysarthro-dysphonia, stridor, and tongue atrophy with fasciculations. At 63 years of age, genetic testing revealed a single heterozygous variant in the SLC52A3 gene. Although typically autosomal recessive, some individuals with classic symptoms and even response to riboflavin therapy have been found to carry only a single mutation in either the SLC52A2 or SLC52A3 gene. Therefore, given the compatible clinical presentation, a diagnosis of BVVLS was considered after discussion with a center of expertise. Consequently, 10 mg/kg/day of riboflavin supplementation was prescribed for three years, but no significant clinical improvement was observed. Currently, at age 68, the patient is on nocturnal non-invasive mechanical ventilation (NIV) and uses assisted airway clearance techniques, including air-stacking maneuvers and mechanical insufflation-exsufflation on demand, due to respiratory compromise secondary to diaphragmatic weakness and vocal cord paralysis. This unique presentation of slowly progressive symptoms and long survival may be related to the single heterozygous SLC52A3 variant found. Respiratory care in BVVLS is currently adapted from other neuromuscular disorders with stronger evidence bases. This case highlights the critical role of pulmonology in BVVLS care, including clinical and functional monitoring, early initiation of NIV, and the implementation of airway clearance techniques.

Riboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested. Treatment with oral riboflavin (vitamin B2) halts disease progression and can be lifesaving. We hypothesized that patients may have been left unrecognized at the time of presentation and therefore we performed a datamining study to detect undiagnosed RTD patients in a tertiary referral hospital. A systematic search in Electronic Health Records (EHR) of all patients visiting the Amsterdam University Medical Centers between January 2004 and July 2021 was performed by a medical data text-mining tool. Pseudonymized patient records, matching pre-defined search terms (hearing loss or auditory neuropathy spectrum disorders combined with key clinical symptoms or riboflavin) were screened and included if no definitive alternative diagnosis for symptoms indicating possible RTD was found. Included patients were offered genetic testing. We documented total number of patients with possible RTD, number of patients that underwent genetic testing for RTD and results of genetic testing. EHR of 2.288.901 patients were automatically screened. Thirteen patients with possible RTD were identified and offered genetic testing. Seven patients chose not to participate. Genetic testing was performed in 6 patients and was negative. The datamining did detect all previously known RTD patients in the hospital. By screening a large cohort of patients of all ages in a tertiary referral hospital in a period spanning 17 years, no new RTD patients were found. Although not all suspected patients underwent genetic testing, our findings suggest that the prevalence of RTD is low and the chance of having missed this diagnosis in a tertiary referral hospital is limited.

Riboflavin Transporter Deficiency (RTD) is a rare neurological disorder characterized by pontobulbar palsy, hearing loss, and motor cranial nerve involvement. SLC52A3 and SLC52A2 mutations are causes of RTD. SLC52A2 mutations are usually found in childhood onset cases. Fifteen Iranian RTD diagnosed patients without SLC52A2 mutations have been previously described. We aimed to identify causative mutations in two childhood cases. We recruited patients with diagnosis of BVVL. Comprehensive clinical evaluations were performed on the patients. SLC52A3 and SLC52A2 genes were PCR-amplified and Sanger sequenced. Candidate disease causing variations were screened for segregation with disease status in the respective families and control individuals. A novel homozygous SLC52A3 mutation (p.Met1Val) and a heterozygous SLC52A2 mutation (p.Ala288Val) were both observed in one proband with typical RTD presentations. The aggregate of presentations in the early stages of disease in the second patient that included weakness in the lower extremities, absence of bulbar or hearing defects, prominent sensory polyneuropathy as evidenced in electrodiagnostic studies, and absence of sensory symptoms including sensory ataxia did not prompt immediate RTD diagnosis. Dysarthria and decreased hearing manifested later in the disease course. A novel homozygous SLC52A2 (p.Val314Met) mutation was identified. A literature search found recent reports of other atypical RTD presentations. These include MRI findings, speech understanding difficulties accompanied by normal hearing, anemia, and left ventricular non-compaction. Knowledge of unusual presentations lessens the chance of misdiagnosis or delayed RTD diagnosis which, in light of favorable effects of riboflavin supplementation, is of immense importance.