Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Riboflavin and ubiquinone (Coenzyme Q(10), CoQ(10)) deficiencies are heterogeneous groups of autosomal recessive conditions affecting both children and adults. Riboflavin (vitamin B(2))-derived cofactors are essential for the function of numerous dehydrogenases. Genetic defects of the riboflavin transport have been detected in Brown-Vialetto-Van Laere and Fazio-Londe syndromes (C20orf54), and haploinsufficiency of GPR172B has been proposed in one patient to cause persistent riboflavin deficiency. Mutations in the electron tranferring fravoprotein genes (ETFA/ETFB) and its dehydrogenase (ETFDH) are causative for multiple acyl-CoA dehydrogenase deficiency. Mutations in ACAD9, encoding the acyl-CoA dehydrogenase 9 protein were recently reported in mitochondrial disease with respiratory chain complex I deficiency. All these conditions may respond to riboflavin therapy. CoQ(10) is a lipid-soluble component of the cell membranes, where it functions as a mobile electron and proton carrier, but also participates in other cellular processes as a potent antioxidant, and by influencing pyrimidine metabolism. The increasing number of molecular defects in enzymes of the CoQ(10) biosynthetic pathways (PDSS1, PDSS2, COQ2, COQ6, COQ9, CABC1/ADCK3) underlies the importance of these conditions. The clinical heterogeneity may reflect blocks at different levels in the complex biosynthetic pathway. Despite the identification of several primary CoQ(10) deficiency genes, the number of reported patients is still low, and no true genotype-phenotype correlations are known which makes the genetic diagnosis still difficult. Additionally to primary CoQ(10) deficiencies, where the mutation impairs a protein directly involved in CoQ(10) biosynthesis, we can differentiate secondary deficiencies. CoQ(10) supplementation may be beneficial in both primary and secondary deficiencies and therefore the early recognition of these diseases is of utmost importance.
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PMID:Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ 10). 2223 80

Brown-Vialetto-Van Laere syndrome (Online Mendelian Inheritance in Man number 211530) is a neurodegenerative disorder characterized by pontobulbar palsy affecting cranial nerves (mainly VII-XII). Sensorineural deafness is often the leading sign, followed by other neurologic signs. Inheritance is often autosomal recessive, with mutations in the C20orf54 gene (Online Mendelian Inheritance in Man number 613350). Three previous patients with mutations in the C20orf54 gene and clinical signs of Brown-Vialetto-Van Laere or Fazio-Londe syndrome revealed a metabolic profile suggesting a multiple acyl-coenzyme A dehydrogenase defect. They benefited from riboflavin. We describe a 3-year-old girl with early-onset Brown-Vialetto-Van Laere syndrome and a novel mutation in the C20orf54 gene (c.989G>T). On T(2)-weighted imaging, increased signal intensity of the vestibular nuclei bilaterally, the pedunculus cerebellaris superior and the central tegmental tract were observed during acute clinical deterioration. Her metabolic profile was normal. Trials with steroids, immunoglobulins, and riboflavin produced no effect. The patient recovered slowly during subsequent months, with residual deficits. Brown-Vialetto-Van Laere syndrome should be considered in patients with sensorineural hearing loss and pontobulbar palsy. Patients should be screened for riboflavin deficiency and a therapy with riboflavin may provide effective treatment in some affected patients.
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PMID:Brown-Vialetto-Van Laere syndrome: a riboflavin-unresponsive patient with a novel mutation in the C20orf54 gene. 2263 41

Brown-Vialetto-Van Laere syndrome was first described in 1894 as a rare neurodegenerative disorder characterized by progressive sensorineural deafness in combination with childhood amyotrophic lateral sclerosis. Mutations in the gene, SLC52A3 (formerly C20orf54), one of three known riboflavin transporter genes, have recently been shown to underlie a number of severe cases of Brown-Vialetto-Van Laere syndrome; however, cases and families with this disease exist that do not appear to be caused by SLC52A3 mutations. We used a combination of linkage and exome sequencing to identify the disease causing mutation in an extended Lebanese Brown-Vialetto-Van Laere kindred, whose affected members were negative for SLC52A3 mutations. We identified a novel mutation in a second member of the riboflavin transporter gene family (gene symbol: SLC52A2) as the cause of disease in this family. The same mutation was identified in one additional subject, from 44 screened. Within this group of 44 patients, we also identified two additional cases with SLC52A3 mutations, but none with mutations in the remaining member of this gene family, SLC52A1. We believe this strongly supports the notion that defective riboflavin transport plays an important role in Brown-Vialetto-Van Laere syndrome. Initial work has indicated that patients with SLC52A3 defects respond to riboflavin treatment clinically and biochemically. Clearly, this makes an excellent candidate therapy for the SLC52A2 mutation-positive patients identified here. Initial riboflavin treatment of one of these patients shows promising results.
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PMID:Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease. 2274 May 98

Brown-Vialetto-van Laere (BVVL) and Fazio-Londe (FL) are rare and clinically overlapping motor neurons syndromes. Recently BVVL has been associated with mutations in C20orf54/hRFT2 and defective riboflavin transport. We compared clinical and laboratory features of 6 patients (age range 11-17 years), with features of BVVL and FL overlap syndromes. Patients were assessed as following: blood levels of riboflavin and redox status, electrophysiological, neuroradiological and pulmonary studies, ALS functional rating scale and molecular genetic analysis. Two patients manifested deafness at ages of 3 and 10 years, and developed later subacute progressive ponto-bulbar palsy. A third patient markedly improved after intravenous immunoglobulins (IVIG), but then relapsed remaining unresponsive to treatment; he was not deaf although had abnormal auditory evoked responses (BAERs). The remaining 3 patients had no deafness, although likewise manifested subacute progressive ponto-bulbar palsy. We found hRFT2 mutations in 3/6 patients manifesting deafness or abnormal BAERs. No patient had reduced riboflavin blood levels. However, on riboflavin supplementation (10mg/kg/day) the most severely affected BVVL patient stopped progression of symptoms following 8 months of treatment. BVVL and FL are severe progressive diseases with overlapping symptoms although only hRFT2 mutated patients manifest deafness. Riboflavin supplementation seems to stabilize and improve progression of the disease.
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PMID:Brown-Vialetto-van Laere and Fazio-Londe overlap syndromes: a clinical, biochemical and genetic study. 2282 38