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Indian Journal of Clinical Biochemistry... Oct 2023Glutaric aciduria type II, also known as Multiple acyl-CoA Dehydrogenase Deficiency, results from a defect in the mitochondrial electron transport chain resulting in an...
Glutaric aciduria type II, also known as Multiple acyl-CoA Dehydrogenase Deficiency, results from a defect in the mitochondrial electron transport chain resulting in an inability to break down fatty-acids and amino acids. There are three phenotypes- type 1 and 2 are of neonatal onset and severe form, with and without congenital anomalies, respectively, and presents with acidosis, severe hypotonia, cardiomyopathy, hepatomegaly, and non-ketotic hypoglycemia. Type 3 or late-onset Multiple acyl-CoA Dehydrogenase Deficiency usually presents in the adolescent or adult age group with phenotype ranging from mild forms of myopathy and exercise intolerance to severe forms of acute metabolic decompensation on its chronic course. Type 3 Multiple acyl-CoA Dehydrogenase Deficiency rarely presents in infancy and in liver failure. We present a five-month-old developmentally normal female child with acute encephalopathy, hypotonia, non-ketotic hypoglycemia, metabolic acidosis, and liver failure, with a history of sibling death of suspected inborn error of metabolism. The blood acyl-carnitine levels in Tandem Mass Spectrometry and urinary organic acid analysis through Gas Chromatography-Mass Spectrometry were unremarkable. The patient initially responded to riboflavin, CoQ, and supportive management but ultimately succumbed to sepsis with shock and multi-organ dysfunction. The clinical exome sequencing reported a homozygous missense variation in exon 11 of the gene (chr4:g.158706270C > T) that resulted in the amino acid substitution of Leucine for Proline at codon 456 (p.Pro456Leu) suggestive of Glutaric aciduria type IIc (OMIM#231,680).
PubMed: 37746538
DOI: 10.1007/s12291-021-01007-7 -
The American Journal of Case Reports Oct 2023BACKGROUND Brown-Vialetto-Van Laere (BVVL) syndrome is a rare autosomal recessive disorder caused by mutations in intestinal riboflavin transporter genes, resulting in a...
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.
Topics: Female; Infant; Humans; Child, Preschool; Cochlear Implantation; Cochlear Implants; Speech; Hearing Loss, Sensorineural; Bulbar Palsy, Progressive; Riboflavin; Deafness
PubMed: 37786244
DOI: 10.12659/AJCR.940439 -
Journal of Clinical Neuromuscular... Mar 2024Neuromuscular disorders could have respiratory involvement early or late into illness. Rarely, patients may present with a hypercapnic respiratory failure (with minimal... (Review)
Review
OBJECTIVES
Neuromuscular disorders could have respiratory involvement early or late into illness. Rarely, patients may present with a hypercapnic respiratory failure (with minimal motor signs) unmasking an underlying disease. There are hardly any studies which have addressed the spectrum and challenges involved in management of this subset, especially in the real-world scenario.
METHODS
A retrospective study comprising consecutive patients hospitalized with hypercapnic respiratory failure as the sole/dominant manifestation. The clinical-electrophysiological spectrum, phrenic conductions, diaphragm thickness, and outcomes were analyzed.
RESULTS
Twenty-seven patients were included, the mean age was 47.29 (SD 15.22) years, and the median duration of respiratory symptoms was 2 months (interquartile range [IQR] 1-4). Orthopnea was present in 23 patients (85.2%) and encephalopathy in 8 patients (29.6%). Phrenic nerve latencies and amplitudes were abnormal in 83.3% and 95.6%, respectively. Abnormal diaphragm thickness was noted in 78.5%. Based on a comprehensive electrophysiological strategy and paraclinical tests, an etiology was established in all. Reversible etiologies were identified in 17 patients (62.9%). These included myasthenia gravis (anti-AChR and MuSK), inflammatory myopathy, riboflavin transporter deficiency neuronopathy, Pompe disease, bilateral phrenic neuritis, and thyrotoxicosis. Respiratory onset motor neuron disease was diagnosed in 8 patients (29.6%). Despite diaphragmatic involvement, a functional respiratory recovery was noted at discharge (45%) and last follow-up (60%). Predictors for good outcomes included female sex, normal nerve conductions, and recent-onset respiratory symptoms.
DISCUSSION
A good functional recovery was noted in most of the patients including respiratory onset motor neuron disease. A systematic algorithmic approach helps in proper triaging, early diagnosis, and treatment. Clinical and electrodiagnostic challenges and observations from a tertiary care referral center are discussed.
Topics: Humans; Female; Middle Aged; Tertiary Care Centers; Retrospective Studies; Neuromuscular Diseases; Respiratory Insufficiency; Bulbar Palsy, Progressive
PubMed: 38441928
DOI: 10.1097/CND.0000000000000465 -
Journal of Human Genetics Apr 2024Lipid storage myopathy (LSM) is a heterogeneous group of lipid metabolism disorders predominantly affecting skeletal muscle by triglyceride accumulation in muscle...
Lipid storage myopathy (LSM) is a heterogeneous group of lipid metabolism disorders predominantly affecting skeletal muscle by triglyceride accumulation in muscle fibers. Riboflavin therapy has been shown to ameliorate symptoms in some LSM patients who are essentially concerned with multiple acyl-CoA dehydrogenation deficiency (MADD). It is proved that riboflavin responsive LSM caused by MADD is mainly due to ETFDH gene variant (ETFDH-RRMADD). We described here a case with riboflavin responsive LSM and MADD resulting from FLAD1 gene variants (c.1588 C > T p.Arg530Cys and c.1589 G > C p.Arg530Pro, FLAD1-RRMADD). And we compared our patient together with 9 FLAD1-RRMADD cases from literature to 106 ETFDH-RRMADD cases in our neuromuscular center on clinical history, laboratory investigations and pathological features. Furthermore, the transcriptomics study on FLAD1-RRMADD and ETFDH-RRMADD were carried out. On muscle pathology, both FLAD1-RRMADD and ETFDH-RRMADD were proved with lipid storage myopathy in which atypical ragged red fibers were more frequent in ETFDH-RRMADD, while fibers with faint COX staining were more common in FLAD1-RRMADD. Molecular study revealed that the expression of GDF15 gene in muscle and GDF15 protein in both serum and muscle was significantly increased in FLAD1-RRMADD and ETFDH-RRMADD groups. Our data revealed that FLAD1-RRMADD (p.Arg530) has similar clinical, biochemical, and fatty acid metabolism changes to ETFDH-RRMADD except for muscle pathological features.
Topics: Humans; Acyl Coenzyme A; Electron-Transferring Flavoproteins; Iron-Sulfur Proteins; Lipid Metabolism, Inborn Errors; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Muscular Dystrophies; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Riboflavin
PubMed: 38228875
DOI: 10.1038/s10038-023-01216-3 -
Plant Physiology and Biochemistry : PPB May 2024Riboflavins are secreted under iron deficiency as a part of the iron acquisition Strategy I, mainly when the external pH is acidic. In plants growing under Fe-deficiency...
Riboflavins are secreted under iron deficiency as a part of the iron acquisition Strategy I, mainly when the external pH is acidic. In plants growing under Fe-deficiency and alkaline conditions, riboflavins have been reported to accumulate inside the roots, with very low or negligible secretion. However, the fact that riboflavins may undergo hydrolysis under alkaline conditions has been so far disregarded. In this paper, we report the presence of riboflavin derivatives and products of their alkaline hydrolysis (lumichrome, lumiflavin and carboxymethylflavin) in nutrient solutions of Cucumis sativus plants grown under different iron regimes (soluble Fe-EDDHA in the nutrient solution, total absence of iron in the nutrient solution, or two different doses of FeSO supplied as a foliar spray), either cultivated in slightly acidic (pH 6) or alkaline (pH 8.8, 10 mM bicarbonate) nutrient solutions. The results show that root synthesis and exudation of riboflavins is controlled by shoot iron status, and that exuded riboflavins undergo hydrolysis, especially at alkaline pH, with lumichrome being the main product of hydrolysis.
Topics: Plant Roots; Hydrolysis; Cucumis sativus; Iron Deficiencies; Riboflavin; Hydrogen-Ion Concentration; Stress, Physiological; Iron; Plant Exudates
PubMed: 38569423
DOI: 10.1016/j.plaphy.2024.108573 -
Molecular Genetics and Metabolism Jun 2024Glutaric aciduria type II (GAII) is a heterogeneous genetic disorder affecting mitochondrial fatty acid, amino acid and choline oxidation. Clinical manifestations vary...
Glutaric aciduria type II (GAII) is a heterogeneous genetic disorder affecting mitochondrial fatty acid, amino acid and choline oxidation. Clinical manifestations vary across the lifespan and onset may occur at any time from the early neonatal period to advanced adulthood. Historically, some patients, in particular those with late onset disease, have experienced significant benefit from riboflavin supplementation. GAII has been considered an autosomal recessive condition caused by pathogenic variants in the gene encoding electron-transfer flavoprotein ubiquinone-oxidoreductase (ETFDH) or in the genes encoding electron-transfer flavoprotein subunits A and B (ETFA and ETFB respectively). Variants in genes involved in riboflavin metabolism have also been reported. However, in some patients, molecular analysis has failed to reveal diagnostic molecular results. In this study, we report the outcome of molecular analysis in 28 Australian patients across the lifespan, 10 paediatric and 18 adult, who had a diagnosis of glutaric aciduria type II based on both clinical and biochemical parameters. Whole genome sequencing was performed on 26 of the patients and two neonatal onset patients had targeted sequencing of candidate genes. The two patients who had targeted sequencing had biallelic pathogenic variants (in ETFA and ETFDH). None of the 26 patients whose whole genome was sequenced had biallelic variants in any of the primary candidate genes. Interestingly, nine of these patients (34.6%) had a monoallelic pathogenic or likely pathogenic variant in a single primary candidate gene and one patient (3.9%) had a monoallelic pathogenic or likely pathogenic variant in two separate genes within the same pathway. The frequencies of the damaging variants within ETFDH and FAD transporter gene SLC25A32 were significantly higher than expected when compared to the corresponding allele frequencies in the general population. The remaining 16 patients (61.5%) had no pathogenic or likely pathogenic variants in the candidate genes. Ten (56%) of the 18 adult patients were taking the selective serotonin reuptake inhibitor antidepressant sertraline, which has been shown to produce a GAII phenotype, and another two adults (11%) were taking a serotonin-norepinephrine reuptake inhibitor antidepressant, venlafaxine or duloxetine, which have a mechanism of action overlapping that of sertraline. Riboflavin deficiency can also mimic both the clinical and biochemical phenotype of GAII. Several patients on these antidepressants showed an initial response to riboflavin but then that response waned. These results suggest that the GAII phenotype can result from a complex interaction between monoallelic variants and the cellular environment. Whole genome or targeted gene panel analysis may not provide a clear molecular diagnosis.
PubMed: 38941880
DOI: 10.1016/j.ymgme.2024.108516 -
Genes & Diseases Jul 2024
PubMed: 38515939
DOI: 10.1016/j.gendis.2023.06.038 -
Bioelectrochemistry (Amsterdam,... Jun 2024The primary objective of this study is to elucidate the synergistic effect of an exogenous redox mediator and carbon starvation on the microbiologically influenced...
The primary objective of this study is to elucidate the synergistic effect of an exogenous redox mediator and carbon starvation on the microbiologically influenced corrosion (MIC) of metal nickel (Ni) by nitrate reducing Pseudomonas aeruginosa. Carbon source (CS) starvation markedly accelerates Ni MIC by P. aeruginosa. Moreover, the addition of exogenous riboflavin significantly decreases the corrosion resistance of Ni. The MIC rate of Ni (based on corrosion loss volume) is ranked as: 10 % CS level + riboflavin > 100 % CS level + riboflavin > 10 % CS level > 100 % CS level. Notably, starved P. aeruginosa biofilm demonstrates greater aggressiveness in contributing to the initiation of surface pitting on Ni. Under CS deficiency (10 % CS level) in the presence of riboflavin, the deepest Ni pits reach a maximum depth of 11.2 μm, and the corrosion current density (i) peak at approximately 1.35 × 10 A·cm, representing a 2.6-fold increase compared to the full-strength media (5.25 × 10 A·cm). For the 10 % CS and 100 % CS media, the addition of exogenous riboflavin increases the Ni MIC rate by 3.5-fold and 2.9-fold, respectively. Riboflavin has been found to significantly accelerate corrosion, with its augmentation effect on Ni MIC increasing as the CS level decreases. Overall, riboflavin promotes electron transfer from Ni to P. aeruginosa, thus accelerating Ni MIC.
Topics: Pseudomonas aeruginosa; Nickel; Corrosion; Carbon; Riboflavin; Biofilms
PubMed: 38471411
DOI: 10.1016/j.bioelechem.2024.108679 -
Maternal & Child Nutrition Jan 2024Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and...
Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRac and ThDP. Other risk factors for women were lower BMI, mid-upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron-containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDP and alpha-1-acid-glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic, dietary and health care-seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children.
Topics: Adult; Female; Humans; Male; Pregnancy; Young Adult; Anemia; Anemia, Iron-Deficiency; Ferritins; Hemoglobins; Laos; Prevalence; Risk Factors; Thiamine Deficiency
PubMed: 37803889
DOI: 10.1111/mcn.13565 -
Frontiers in Pediatrics 2024Riboflavin transporter deficiency (RTD) is a rare genetic disorder that affects riboflavin transport, leading to impaired red blood cell production and resulting in pure...
INTRODUCTION
Riboflavin transporter deficiency (RTD) is a rare genetic disorder that affects riboflavin transport, leading to impaired red blood cell production and resulting in pure red cell aplasia. Recognizing and understanding its clinical manifestations, diagnosis, and management is important.
CASE PRESENTATION
A 2-year-old patient presented with pure red cell aplasia as the primary symptom of RTD. After confirming the diagnosis, rapid reversal of anemia was achieved after high-dose riboflavin treatment.
CONCLUSION
RTD often has an insidious onset, and neurological symptoms appear gradually as the disease progresses, making it prone to misdiagnosis. Genetic testing and bone marrow biopsy can confirm the diagnosis.
PubMed: 38694724
DOI: 10.3389/fped.2024.1391245