A Brazilian family with Brown-Vialetto-van Laere syndrome with autosomal recessive inheritance

Malheiros, José Augusto; Camargos, Sarah Teixeira; Oliveira, José Teotônio de; Cardoso, Francisco

doi:10.1590/s0004-282x2007000100008

Cited by 10 publications

(13 citation statements)

References 18 publications

(23 reference statements)

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“…This finding is in contrast to reports of hyperintensity of brainstem nuclei (Koul et al , 2006; Malheiros et al , 2007), atrophy of the brainstem (Francis et al , 1993; Koc et al , 2003; Malheiros et al , 2007) and atrophy of the cerebellum (Francis et al , 1993; Koc et al , 2003) in genetically undifferentiated cohorts of patients with Brown-Vialetto-Van Laere syndrome.…”

Section: Resultscontrasting

confidence: 99%

Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2

Foley

Menezes

Pandraud

et al. 2013

Brain

146

219

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Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss and respiratory insufficiency. There has been no treatment for this progressive neurodegenerative disorder, which leads to respiratory failure and usually death during childhood. We recently reported the identification of SLC52A2, encoding riboflavin transporter RFVT2, as a new causative gene for Brown-Vialetto-Van Laere syndrome. We used both exome and Sanger sequencing to identify SLC52A2 mutations in patients presenting with cranial neuropathies and sensorimotor neuropathy with or without respiratory insufficiency. We undertook clinical, neurophysiological and biochemical characterization of patients with mutations in SLC52A2, functionally analysed the most prevalent mutations and initiated a regimen of high-dose oral riboflavin. We identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy (manifesting with sensory ataxia, severe weakness of the upper limbs and axial muscles with distinctly preserved strength of the lower limbs), hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression, and we report the response to high-dose oral riboflavin therapy in patients with SLC52A2 mutations, including significant and sustained clinical and biochemical improvements in two patients and preliminary clinical response data in 13 patients with associated biochemical improvements in 10 patients. The clinical and biochemical responses of this SLC52A2-specific cohort suggest that riboflavin supplementation can ameliorate the progression of this neurodegenerative condition, particularly when initiated soon after the onset of symptoms.

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Section: Resultscontrasting

confidence: 99%

Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2

Foley

Menezes

Pandraud

et al. 2013

Brain

146

219

View full text Add to dashboard Cite

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“…Investigations are usually done to exclude other causes or confirm the clinical signs of the patients. Neurophysiological studies show changes consistent with chronic [ 5 , 7 , 9 , 11 - 14 , 16 , 21 , 22 , 25 , 28 , 33 ] or active [ 6 - 8 , 15 , 19 , 20 , 24 , 26 , 27 , 29 , 33 ] denervation in muscles. Motor nerve conduction velocities are usually normal.…”

Section: Diagnosismentioning

confidence: 96%

“…Several other neurological features have been seen in patients with BVVL. Abnormalities of the fundi that have been reported include optic atrophy [ 5 , 13 , 20 , 21 , 27 ], retinitis pigmentosa [ 22 ] and macular hyperpigmentation [ 25 ]. Autonomic dysfunction [ 2 , 13 , 28 , 29 ], epilepsy [ 2 , 18 ], mental retardation [ 1 , 2 , 25 ], reduced horizontal eye movements [ 6 ] and tremor [ 9 , 25 ] have also been associated with BVVL.…”

Section: Clinical Descriptionmentioning

confidence: 99%

“…Of the non-neurological features, respiratory compromise is the most common in BVVL [ 4 - 13 , 15 , 17 , 19 - 21 , 24 , 27 - 33 ]. Other non-neurological features that have been reported include auditory hallucinations [ 2 ], behavioral changes [ 27 ], color blindness [ 20 ], diabetes insipidus [ 1 ], delayed puberty and hypogonadism [ 16 ], dysmorphic features [ 25 ], gynecomastia [ 16 ] and hypertension [ 11 , 33 ]. In some cases, no other associated non-neurological features were reported [ 34 - 38 ].…”

Section: Clinical Descriptionmentioning

confidence: 99%

“…Visual evoked potentials performed in 15 cases showed normal values in seven patients [ 9 , 14 , 25 , 28 , 32 , 33 ] and prolonged latencies in the rest [ 5 , 7 , 10 , 12 , 13 , 15 , 19 , 21 , 29 ]. Brainstem auditory evoked potentials were abnormal when performed in 17 cases [ 4 , 5 , 8 , 10 , 12 - 15 , 21 , 25 , 27 , 32 , 33 ]. When carried out, audiometry universally showed sensorineural deafness.…”

Section: Diagnosismentioning

confidence: 99%

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