A Case Report of Riboflavin Treatment and Cochlear Implants in a 4-Year-Old Girl with Progressive Hearing Loss and Delayed Speech Development: Brown-Vialetto-Van Laere Syndrome.

BACKGROUND Brown-Vialetto-Van Laere (BVVL) syndrome is a rare autosomal recessive disorder caused by mutations in intestinal riboflavin transporter genes, resulting in a motor neuron disorder of childhood, which can be associated with sensorineural deafness. This report describes a 4-year-old Polish girl with progressive hearing loss and delayed speech development diagnosed with Brown-Vialetto-Van Laere syndrome who was treated with riboflavin (vitamin B2) and cochlear implants. CASE REPORT The case report concerns a girl from Poland who, at the age of 2 years 10 months, developed progressive atypical neurological symptoms of unknown etiology: ataxia of the upper and lower limbs, gait abnormalities, generalized muscle weakness, visual and hearing problems, and regression of speech development. A karyotype study (whole-exome sequencing) revealed alterations within SLC52A2, leading to the diagnosis of Brown-Vialetto-Van Laere syndrome and initiation of high-dose riboflavin treatment. As a 4-year-old child, she presented to the Institute of Physiology and Pathology of Hearing - World Hearing Center in Poland with progressive hearing loss and speech regression. Hearing tests revealed bilateral profound sensorineural hearing loss with auditory neuropathy. Surgical treatment was applied in the form of bilateral cochlear implantation. CONCLUSIONS This report shows the importance of genetic testing in infants who present with atypical symptoms or signs. In this case, the diagnosis of Brown-Vialetto-Van Laere syndrome resulted in timely correction of the genetic riboflavin (vitamin B2) deficiency and improved hearing following the use of cochlear implants.

Acute Thyrotoxic Myopathy Combined with Neck Pain: A Case Report.

INTRODUCTION: Acute thyrotoxic myopathy (ATM) is a rare and potentially lethal complication of thyrotoxicosis. The typical clinical symptoms of ATM are characterized by bulbar paralysis. Reports of the successful treatment of ATM are sporadic due to its low incidence. However, no English literature has reported Chinese patients with ATM and neck pain. Here, we report for the first time a Chinese patient with ATM and neck pain who recovered through large doses of systemic glucocorticoids and one intrathyroidal steroid injection. CASE REPORT: A 23-year-old woman visited our hospital with a two-year history of progressive weakness of her bulbar muscles, hoarseness, cough when swallowing, dysphagia, and a one-month history of recurrent painful swelling of the thyroid gland. She was diagnosed with ATM, chronic thyrotoxic myopathy (CTM), and Graves' ophthalmopathy (GO) due to Graves' disease (GD). After she was treated with a combination of low-dose glucocorticoids, antithyroid drugs (ATDs), propranolol, and ultrasound-guided percutaneous intrathyroidal injection of glucocorticoids, her bulbar paralysis, proximal myopathy, and neck pain simultaneously improved without recurrence during follow-up. To our knowledge, this is the first case report of a patient with ATM, CTM, GD, GO and neck pain treated by administering a combination of low-dose glucocorticoids, one intrathyroidal steroid injection and antithyroid agents. CONCLUSIONS: Clinicians should consider ATM and intervene with aggressive glucocorticoid therapy, and this is the key to reversing the progression of ATM when a patient has bulbar paralysis and thyrotoxic symptoms. Our case report references the clinical diagnosis and treatment of such cases.

An Analysis of Respiratory Muscle Paralysis of Adult Patients in Guillain-Barré Syndrome: A Retrospective Analysis.

Respiratory muscle paralysis is known as a very common complication of Guillain-Barré syndrome (GBS). However, most research has focused on its later stages rather than its earlier stages, including the prognosis of patients with this condition, or factors that act as early predictors of risk. Therefore, our study aimed to identify early predictors of respiratory muscle paralysis in patients with GBS and determine the short-term prognosis of such patients. We recruited 455 GBS patients (age ≥ 18) who had been hospitalized in the First Affiliated Hospital of Harbin Medical University between 2016 and 2021, retrospectively. We recorded clinical and laboratory data and used linear and logistic regression analysis to investigate the relationship between early clinical, examination results, and subsequent respiratory muscle paralysis. Among the 455 patients, 129 were assigned to a respiratory muscle paralysis group and 326 were assigned to a non-respiratory muscle paralysis group. Compared with the non-affected group, the time from onset to admission was shorter (p = 0.0003), and the Medical Research Council (MRC) score at admission and discharge was smaller in the affected group (p < 0.0001). Compared with the non-affected group, the affected group had higher Hughes and Erasmus GBS Respiratory Insufficiency Score (EGRIS) scores at admission and longer hospital stays (p < 0.0001). Patients in the affected group were more likely to have bulbar palsy and lung infections (p < 0.0001). To conclude, bulbar palsy, a higher EGRIS score and Hughes score at admission, a lower MRC score, and a shorter time between onset and admission, are all predictive risk factors for respiratory muscle paralysis in patients with GBS. An increase in any of these factors increases the risk of muscle paralysis. Patients with respiratory muscle paralysis have a poorer short-term prognosis than those without respiratory muscle paralysis. Therefore, we should attempt to identify patients with one or more of these characteristics in the early stages of admission, provide ventilation management, and administer IMV treatment if necessary.

Anti-GT1a and anti-GQ1b immunoglobulin G antibody positivity with overlapping Miller Fisher/Guillain-Barré syndromes and prominent headache: a case report.

Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) are acute immune-mediated peripheral neuropathies. In addition to their classic presentations, a variety of other signs and symptoms have been reported; however, headache appears to be relatively uncommon. We describe a 53-year-old woman who presented with acute bulbar palsy as the first symptom of overlapping MFS/GBS accompanied by severe headache. The first important clinical impairment of the patient was acute bulbar palsy along with prominent headache, without limb weakness. Although her initial diagnosis was acute bulbar palsy plus, she subsequently developed lower limb diffuse weakness, and her final clinical diagnosis was overlapping MFS/GBS. Anti-ganglioside antibodies were positive for anti-GQ1b and anti-GT1a immunoglobulin G. The patient received intravenous immunoglobulin on day 2 of admission. Early identification of these overlapping syndromes is important for the management of patients, to avoid respiratory failure or severe weakness with axonal degeneration. We therefore remind clinicians of the importance of further examination in patients with headache and acute bulbar palsy of unknown origin.

Cochlear Implant in Brown-Vialetto-Van Laere Syndrome Patient.

The Brown-Vialetto-Van Laere syndrome or the riboflavin transporter deficiency syndrome is a neurodegenerative disorder initially reported by Brown in 1894, by Vialetto in 1936, and by Van Laere in 1966. The syndrome has been described in more than 100 patients since then. Hearing loss is the most common symptom of the syndrome, as most individuals have it through the development of the disease. Although there is a variation between the onset of hearing loss and the other possible symptoms, hearing loss usually begins in early childhood. Nevertheless, there are some cases describing hearing loss starting in adults. Hereby, we present a case report of a patient who started having the symptoms at the age of 14 and who had a mutation in the SLC52A3 gene, presenting with sensorineural hearing loss associated with cerebellar ataxia, who also underwent successful cochlear implant surgery.

Clinical predictors and electrodiagnostic characteristics in patients with Guillain-Barré syndrome with respiratory failure: a retrospective, matched case-control study.

BACKGROUND: Respiratory failure is a common complication of Guillain-Barré syndrome (GBS). This study aimed to determine the clinical predictors and electrodiagnostic (EDx) characteristics in patients with Guillain-Barré syndrome (GBS) with respiratory failure. METHODS: The retrospective study included 29 confirmed GBS cases with respiratory failure and age- (±5 years) and sex-matched controls (1:1). The dependent t-test and McNemar-Bowker test were used to analyse the continuous and categorical data, respectively. In addition, a multiple logistic regression analysis was used to analyse the predictive factors for respiratory failure. RESULTS: Among both cases and controls, the majority were male (72.4%), and the average age was 50.9 years. The data showed that patients with respiratory failure had higher GBS disability scores, lower motor power (≤3) of the hip flexors and ankle dorsiflexors, and experienced facial and bulbar palsy. In the multivariate analysis, the significant predictive factors were bulbar palsy (AOR 10.4 [95% CI [2.6-41.4]) and motor power of hip flexors ≤ 3 (AOR 31.4 [95% CI [3.1-314.5]). Patients with respiratory failure had lower compound muscle action potential amplitude of the ulnar and tibial nerves. The median, ulnar, and tibial nerve conduction studies were more likely to reflect inexcitability. The GBS subtypes in GBS patients with and without respiratory failure were not significantly different. CONCLUSIONS: Bulbar palsy and motor power of the hip flexors ≤ 3 were significant predictors for respiratory failure. The GBS subtypes in patients with and without respiratory failure were not significantly different.

Isolated bulbar palsy and dysphagia in children with respiratory symptoms.

Oropharyngeal dysphagia can cause chronic aspiration leading to significant respiratory symptoms. When dysphagia is diagnosed, an underlying cause is sought. We present a case series of 15 children diagnosed aged 6 months to 5 years (mean 2y 5mo; 11 males, four females) over a 6-year period, who were found to have an isolated bulbar palsy on genioglossus electromyography, with no accompanying neurological or neurodevelopmental disorder. Eight children had dysphagia but a normal EMG. In those with isolated bulbar palsy, management included thickened fluids (n=13), cooled boiled water (n=1), and nasogastric tube feeding (n=1). Follow-up over 1 to 8 years (mean 5y) showed complete resolution in six children, improvement in four children, and no improvement in five children (including two requiring fluids via a gastrostomy). Eight children no longer had any respiratory symptoms. Isolated bulbar palsy is under-recognized and has not been reported previously as a cause of significant dysphagia in children.

Acute Bulbar Palsy and Ophtalmoplegia Associated With Anti-GT1a IgG Antibodies.

INTRODUCTION: Although several variants of Guillain-Barré syndrome (GBS) have been described, they are uncommon, and the atypical clinical presentation of patients makes the diagnosis challenging. This article reports a case of acute bulbar palsy plus (ABPp) syndrome. CASE REPORT: A 18-year-old patient was admitted to our hospital because of difficulty swallowing, slurred speech, tingling of the extremities of the 4 limbs, and diplopia. He reported abdominal pain and diarrhea 2 weeks earlier. Physical examination showed a low-pitched voice, palsy elevation of the soft palate and complete palsy of the abduction of the left eye. Electromyography and cerebrospinal fluid examination were unremarkable, but Campylobacter jejuni serology was positive, and we found an isolated immunoglobulin G (IgG) anti-GT1a antibodies positivity. A diagnosis of ABPp was finally made, and the patient fully recovered early after receiving polyvalent immunoglobulins infusion. CONCLUSIONS: ABPp is classified as subtype of GBS. The most frequent clinical signs of ABPp are ophthalmoplegia, facial palsy, and ataxia. IgG anti-GT1a and/or anti-GQ1b are positive in a majority of patients with ABPp; however, these antibodies are not specific and can found in other subtypes of GBS.

The audiovestibular profile of Brown-Vialetto-Van Laere syndrome.

BACKGROUND: Brown-Vialetto-Van Laere syndrome, a rare disorder associated with motor, sensory and cranial nerve neuropathy, is caused by mutations in riboflavin transporter genes SLC52A2 and SLC52A3. Hearing loss is a characteristic feature of Brown-Vialetto-Van Laere syndrome and has been shown in recent studies to be characterised by auditory neuropathy spectrum disorder. METHOD: This study reports the detailed audiovestibular profiles of four cases of Brown-Vialetto-Van Laere syndrome with SLC52A2 and SLC52A3 mutations. All of these patients had auditory neuropathy spectrum disorder. RESULTS: There was significant heterogeneity in vestibular function and in the benefit gained from cochlear implantation. The audiological response to riboflavin therapy was also variable, in contrast to generalised improvement in motor function. CONCLUSION: We suggest that comprehensive testing of vestibular function should be conducted in Brown-Vialetto-Van Laere syndrome, in addition to serial behavioural audiometry as part of the systematic examination of the effects of riboflavin.

Clinical Profile and Predictors of Mechanical Ventilation in Guillain-Barre Syndrome in North Indian Children.

OBJECTIVE: To describe the clinical-laboratory profile of pediatric Guillain-Barre syndrome and delineate features associated with need of mechanical ventilation. METHODS: In a prospective observational study at tertiary care hospital, clinical-laboratory assessment and nerve conduction studies were documented in consecutive children hospitalized with Guillain-Barre syndrome according to Brighton criteria. Clinical-laboratory features were compared between ventilated and nonventilated patients using univariate and multivariate analysis. RESULTS: Forty-six children (27 boys) with a mean age of 69.1±35.2 months were enrolled. History of preceding infection was present in 47.8%, bulbar palsy in 43.5%, feeble voice in 41.3%, sensory involvement in 13%, and autonomic involvement in 39.5%. Tetraparesis was noted in 87% of cases. Hughes disability scale >3 was noted in 44 children at admission and 39 (84.7%) at discharge. The most common electrophysiological type was acute motor axonal neuropathy (46.5%) followed by acute motor sensory axonal neuropathy (39.5%), acute inflammatory demyelinating polyneuropathy (7%), and inexcitable nerves (7%). Nine (19.7%) children were ventilated, 3 (6.5%) died or were lost, and 43 were discharged. Factors associated with need of mechanical ventilation on univariate analysis were older age, hypertension, bulbar palsy, feeble voice, lower Medical Research Council (MRC) sum, raised total leucocyte count, and history of preceding infection. Logistic regression revealed older age, history of predisposing illness, lower MRC sum at presentation, and bulbar palsy as independent predictors of mechanical ventilation. CONCLUSIONS: The most common electrophysiological subtype in northern Indian children is acute motor axonal neuropathy. Older age, preceding infection, low MRC sum, and bulbar palsy are predictors of mechanical ventilation in pediatric Guillain-Barre syndrome.

The Clinical Journey of Patients with Riboflavin Transporter Deficiency Type 2.

PURPOSE: To identify symptoms and health care interactions with patients with riboflavin transporter deficiency (RTD) type 2 prior to diagnosis. METHODS: Parents of children with riboflavin transporter deficiency type 2 (n = 10) were interviewed to collect data on the patient's clinical journey. RESULTS: The average diagnostic delay was 27.6 months. Neurologists were the most commonly visited clinician (90%). Common symptoms during the first year of the patient's clinical journey included abnormal gait and/or ataxia (70%), nystagmus (50%), and upper body muscle weakness (40%). Prior to diagnosis, optic atrophy, sleep apnea, breath-holding spells, and dysphagia were commonly observed. Hearing loss was only reported in 40% of subjects prior to diagnosis. Riboflavin responsive megaloblastic anemia is reported for the first time. Mitochondrial disease was the most common suspected diagnosis (30%). CONCLUSION: Despite clinical variability, common early symptoms of riboflavin transporter deficiency type 2 exist that can better allow clinicians to more rapidly identify riboflavin transporter deficiency type 2.

Relationship between oral transit time and functional performance in motor neuron disease.

Oral phase swallowing impairment in motor neuron disease (MND) is caused by tongue weakness, fasciculation and atrophy, which may compromise oral transit time and total feeding time. OBJECTIVE To describe and correlate total oral transit time (TOTT) with functional performance in MND using different food consistencies. METHODS The study was conducted on 20 patients with MND, regardless of type or duration of the disease, of whom nine were excluded due to issues on the videofluoroscopic swallowing images. The remaining 11 patients (nine men and two women) ranged from 31 to 87 years of age (mean: 57 years) with scores on the Penetration Aspiration Scale ranging from ≤ 2 to ≤ 4. The Amyotrophic Lateral Sclerosis Functional Rating Scale - revised questionnaire was applied to classify individuals according to global, bulbar and bulbar/respiratory parameters. Videofluoroscopy of swallowing using 5ml of different consistencies was performed and a quantitative temporal analysis of the TOTT was carried out with the aid of specific software. RESULTS There was a wide variation in the TOTT within the same food consistency among MND patients. There was a correlation between the TOTT and overall functional performance for the thickened liquid consistency (r = -0.691) and between the TOTT and bulbar performance for the pureed consistency (r = -0.859). CONCLUSION Total oral transit time in MND varies within the same food consistency and the longer the TOTT, regardless of food consistency, the lower the functional performance in MND.

Relationship between oral transit time and functional performance in motor neuron disease / Relação entre tempo de trânsito oral e desempenho funcional na doença do neurônio motor

ABSTRACT Oral phase swallowing impairment in motor neuron disease (MND) is caused by tongue weakness, fasciculation and atrophy, which may compromise oral transit time and total feeding time. Objective: To describe and correlate total oral transit time (TOTT) with functional performance in MND using different food consistencies. Methods: The study was conducted on 20 patients with MND, regardless of type or duration of the disease, of whom nine were excluded due to issues on the videofluoroscopic swallowing images. The remaining 11 patients (nine men and two women) ranged from 31 to 87 years of age (mean: 57 years) with scores on the Penetration Aspiration Scale ranging from ≤ 2 to ≤ 4. The Amyotrophic Lateral Sclerosis Functional Rating Scale - revised questionnaire was applied to classify individuals according to global, bulbar and bulbar/respiratory parameters. Videofluoroscopy of swallowing using 5ml of different consistencies was performed and a quantitative temporal analysis of the TOTT was carried out with the aid of specific software. Results: There was a wide variation in the TOTT within the same food consistency among MND patients. There was a correlation between the TOTT and overall functional performance for the thickened liquid consistency (r = −0.691) and between the TOTT and bulbar performance for the pureed consistency (r = −0.859). Conclusion: Total oral transit time in MND varies within the same food consistency and the longer the TOTT, regardless of food consistency, the lower the functional performance in MND.

RESUMO O comprometimento na fase oral da deglutição na doença do neurônio motor (DNM) é ocasionado por fraqueza, fasciculação e atrofia de língua, podendo comprometer o tempo de trânsito oral (TTO) e o tempo total de alimentação. Objetivo: Descrever e relacionar o tempo de trânsito oral total (TTOT) com o desempenho funcional na DNM em distintas consistências de alimento. Métodos: Participaram 20 indivíduos com DNM, independente do tipo ou tempo de doença. Foram incluídos 11 indivíduos, nove homens e duas mulheres, faixa etária de 31 a 87 anos (média de idade de 57 anos) e com Penetration Aspiration Scale (Rosenbek et al., 1996) de ≤ 2 a ≤ 4. Foram excluídos nove indivíduos por questões técnicas relacionadas às imagens videofluoroscópicas de deglutição. Aplicado o questionário Amyotrophic Lateral Sclerosis Functional Rating Scale - revised para classificação dos indivíduos de acordo com parâmetros Global, Bulbar e Bulbar/Respiratório. Realizada videofluoroscopia da deglutição com diferentes consistências de alimento no volume de cinco ml e análise quantitativa do TTOT por meio de software específico. Resultados: Houve ampla variação no TTOT dentro da mesma consistência de alimento na DNM. Houve correlação entre o TTOT e o desempenho funcional global na consistência líquida espessada (r = −0,691) e para o TTOT e o desempenho bulbar na pastosa (r = −0,859). Conclusão: O tempo de trânsito oral total na DNM varia dentro da mesma consistência de alimento e quanto mais longo o TTOT, independente da consistência do alimento, menor foi o desempenho funcional na DNM.

Cochlear implantation in children with auditory neuropathy: Lessons from Brown-Vialetto-Van Laere syndrome.

OBJECTIVE: Brown-Vialetto-Van Laere syndrome (BVVL) is a rare neurodegenerative disorder associated with auditory neuropathy (AN). The decision process for CI in AN is evolving with increasing evidence of efficacy. We evaluated the benefit of CI in children with BVVL syndrome. METHODS: A retrospective study reviewed the pre- and post-operative hearing outcomes of three patients with BVVL who presented for CI. A fourth patient with BVVL who was not suitable for CI is also discussed. The primary outcomes were hearing thresholds and auditory perception. Outcome measurement instruments included visual reinforcement audiometry (VRA) or Play Audiometry (PA), Categories of Auditory Performance (CAP) and Auditory Speech Sound Evaluation (ASSE). Secondary outcomes were parental report (BAPP questionnaire), the perception of our SaLT and compliance. RESULTS: Patient 1 had ASSE levels of 40-45 dB HL 1 year post-operatively, and CAP score had improved from 2 to 5. At 2-year review, aided thresholds were 40 dB at 2-4 kHz. Three months following CI, the CAP score of Patient 2 had improved from 3 to 5. At 6 months, thresholds were 25-30 dB at 2-4 kHz. Single words/phrases are used by both patients and benefit is reported by both families. Patient 3 has recently undergone CI, having been previously rejected at another centre. Three months following CI, his thresholds were 35-40 dB at 2-4 kHz and increased use of sign and vocalization is reported. CONCLUSION: CI in children with AN complicating BVVL has a variable, but a positive effect. Other manifestations of BVVL make measuring benefit challenging, in the absence of a 'bespoke' measurement instrument for children with complex needs. This study provides further evidence for the benefit of CI in children with AN.

Brown-Vialetto-Van Laere syndrome: a novel diagnosis to a common presentation.

Brown-Vialetto-Van Laere syndrome (BVVLS) or riboflavin transporter deficiency (OMIM 211530) is a rare treatable autosomal recessive neurodegenerative disorder. This condition is associated with progressive pontobulbar palsy. We describe the clinical course of a 16-month-old boy with BVVLS and a novel homozygous mutation from Pakistan. Our patient presented with stridor and respiratory insufficiency. Hearing loss which is the most common sign of this condition was absent, making it an unusual presentation of BVVLS. His examination revealed ptosis and tongue fasciculation. His riboflavin receptor mutational analysis showed the homozygous mutation in the SLC52A3 gene. Per oral riboflavin was administered, and subsequently, he was able to be weaned off the ventilator. Now the child is improving and attaining developmental milestones.

Bulbar paralysis associated with Miller-Fisher syndrome and its overlaps in Chinese patients.

The study aimed to determine the incidence and the onset time of bulbar paralysis (BP) associated with Miller-Fisher syndrome (MFS) and its overlaps, to better understand the clinical characteristics among patients with MFS and its overlaps. Medical records from 48 patients with MFS and its overlaps were divided into two groups based on the presence (MFS-BP+) or absence (MFS-BP-) of BP. Their clinical features, laboratory and electrophysiological findings, neuroimaging data, and treatment plan were analyzed and compared between two groups. The incidence of BP associated with MFS and its overlaps was 48%. Eighty-two percent of the patients developed BP within 1 week after the onset of MFS and its overlaps. The cerebrospinal fluid (CSF) protein level in patients was higher in MFS-BP+ than in MFS-BP- group (67.69 ± 26.59 vs. 50.15 ± 20.44 mg/dl; P < 0.05). Frequencies of severe limb weakness, hypoglossal paralysis, disturbance of consciousness, and tracheal intubation required were also significantly higher in MFS-BP+ than in MFS-BP- group. Positive results of anti-GQ1b and anti-GT1b antibodies were all found in MFS-BP+ group. The prevalence of BP in MFS and its overlap was higher, the majority of BP occurred within 7 days after the onset of the disease, and early diagnosis of BP concurrence is helpful to decide the treatment plan.

Exome sequencing establishes a gelsolin mutation as the cause of inherited bulbar-onset neuropathy.

INTRODUCTION: Progressive bulbar motor neuropathy is primarily caused by bulbar-onset ALS. Hereditary amyloidosis type IV also presents with a bulbar neuropathy that mimics motor neuron disease. The disease is prevalent in Finland only and is not commonly included in the differential diagnosis of ALS. METHODS: We studied 18 members of a family in which some had bulbar motor neuropathy, and we performed exome sequencing. RESULTS: Five affected family members were found to have a D187Y substitution in the GSN gene known to cause hereditary amyloidosis type IV. CONCLUSIONS: This American family presented with progressive bulbar neuropathy due to a gelsolin mutation not found in Finland. Hereditary amyloidosis type IV presents with bulbar motor neuropathy and not with peripheral neuropathy as occurs with common forms of amyloidosis. This report demonstrates the power of exome sequencing to determine the cause of rare hereditary diseases with incomplete or atypical phenotypes. Muscle Nerve 56: 1001-1005, 2017.

Auditory neuropathy in Brown-Vialetto-Van Laere syndrome due to riboflavin transporter RFVT2 deficiency.

AIM: Mutations in the genes encoding the riboflavin transporters RFVT2 and RFVT3 have been identified in Brown-Vialetto-Van Laere syndrome, a neurodegenerative disorder characterized by hearing loss and pontobulbar palsy. Treatment with riboflavin has been shown to benefit individuals with the phenotype of RFVT2 deficiency. Understanding the characteristics of hearing loss in riboflavin transporter deficiency would enable early diagnosis and therapy. METHOD: We performed hearing assessments in seven children (from four families) with RFVT2 deficiency and reviewed results from previous assessments. Assessments were repeated after 12 months and 24 months of riboflavin therapy and after cochlear implantation in one individual. RESULTS: Hearing loss in these individuals was due to auditory neuropathy spectrum disorder (ANSD). Hearing loss was identified between 3 years and 8 years of age and progressed rapidly. Hearing aids were not beneficial. Riboflavin therapy resulted in improvement of hearing thresholds during the first year of treatment in those with recent-onset hearing loss. Cochlear implantation resulted in a significant improvement in speech perception in one individual. INTERPRETATION: Riboflavin transporter deficiency should be considered in all children presenting with an auditory neuropathy. Speech perception in children with ANSD due to RFVT2 deficiency may be significantly improved by cochlear implantation.

Chiari malformation, syringomyelia and bulbar palsy in X linked hypophosphataemia.

X linked hypophosphataemia (XLH) is a rare condition with numerous musculoskeletal complications. It may mimic other more familiar conditions, such as vitamin D deficiency, ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis. We describe two cases with Chiari type 1 malformations and syringomyelia, neither of which is well recognised in XLH. The first presented late with the additional complications of spinal cord compression, pseudofracture, renal stones and gross femoroacetabular impingement requiring hip replacement. The second also had bulbar palsy; the first case to be described in this condition, to the best of our knowledge. We wish to raise awareness of the important neurological complications of syringomyelia, Chiari malformation, spinal cord compression and bulbar palsy when treating these patients. We also wish to draw attention to the utility of family history and genetic testing when making the diagnosis of this rare but potentially treatable condition.