Biotinidase biochemical and molecular analyses: Experience at a large reference laboratory.

BACKGROUND: Biotinidase deficiency is caused by absent activity of the biotinidase, encoded by the biotinidase gene (BTD). Affected individuals cannot recycle the biotin, leading to heterogeneous symptoms that are primarily neurological and cutaneous. Early treatment with biotin supplementation can prevent irreversible neurological damage and is recommended for patients with profound deficiency, defined as enzyme activity <10% mean normal (MN). Molecular testing has been utilized along with biochemical analysis for diagnosis and management. In this study, our objective was to correlate biochemical phenotype/enzyme activity to BTD genotype in patients for whom both enzyme and molecular testing were performed at our lab, and to review how the correlations inform on variant severity. METHODS: We analyzed results of biotinidase enzyme analysis and BTD gene sequencing in 407 patients where samples were submitted to our laboratory from 2008 to 2020. RESULTS: We identified 84 BTD variants; the most common was c.1330G>C, and 19/84 were novel BTD variants. A total of 36 patients had enzyme activity <10% of MN and the most common variant found in this group was c.528G>T. No variant was reported in one patient in the profound deficiency group. The most common variant found in patients with enzyme activity more than 10% MN was c.1330G>C. CONCLUSIONS: Although enzyme activity alone may be adequate for diagnosing profound biotinidase deficiency, molecular testing is necessary for accurate carrier screening and in cases where the enzyme activity falls in the range where partial deficiency and carrier status cannot be discriminated.

A new case of sodium-dependent multivitamin transporter defect occurring as a life-threatening condition responsive to early vitamin supplementation and literature review.

BACKGROUND: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms. METHODS: We describe a case report of a 5-month-old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium-dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation). RESULTS: We highlight the life-threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3-hydroxyisovaleric acid (3-HIA) as previously reported in this disease in literature. CONCLUSION: SMVT deficiency is a vitamin-responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening.

Strictosamide ameliorates LPS-induced acute lung injury by targeting ERK2 and mediating NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) ranks among the deadliest pulmonary diseases, significantly impacting mortality and morbidity. Presently, the primary treatment for ALI involves supportive therapy; however, its efficacy remains unsatisfactory. Strictosamide (STR), an indole alkaloid found in the Chinese herbal medicine Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Wutan), has been found to exhibit numerous pharmacological properties, particularly anti-inflammatory effects. AIM OF THE STUDY: This study aimes to systematically identify and validate the specific binding proteins targeted by STR and elucidate its anti-inflammatory mechanism in lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Biotin chemical modification, protein microarray analysis and network pharmacology were conducted to screen for potential STR-binding proteins. The binding affinity was assessed through surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and molecular docking, and the anti-inflammatory mechanism of STR in ALI treatment was assessed through in vivo and in vitro experiments. RESULTS: Biotin chemical modification, protein microarray and network pharmacology identified extracellular-signal-regulated kinase 2 (ERK2) as the most important binding proteins among 276 candidate STR-interacting proteins and nuclear factor-kappaB (NF-κB) pathway was one of the main inflammatory signal transduction pathways. Using SPR, CETSA, and molecular docking, we confirmed STR's affinity for ERK2. In vitro and in vivo experiments demonstrated that STR mitigated inflammation by targeting ERK2 to modulate the NF-κB signaling pathway in LPS-induced ALI. CONCLUSIONS: Our findings indicate that STR can inhibit the NF-κB signaling pathway to attenuate LPS-induced inflammation by targeting ERK2 and decreasing phosphorylation of ERK2, which could be a novel strategy for treating ALI.

Clinical Implications of Dietary Probiotic Supplement (Associated with L-Glutamine and Biotin) in Ulcerative Colitis Patients' Body Composition and Quality of Life.

Patients with ulcerative colitis (UC) are reported to have changes in body structure, with negative impact on the course of disease. This study explored the effects of a standardized nutritional supplement containing five bacterial strains of at least five billion bacteria (Bifidobacterium infantis, Bifidobacterium animalis, Lactobacillus bulgaricus, Lactobacillus helveticus, and Enterococcus faecium), L-glutamine, and biotin on the body composition and quality of life of patients with UC. Ninety-three patients over 18 years of age with a confirmed diagnosis of UC, for whom body composition could be accurately determined, were included in this observational follow-up randomized study. These patients were split into two groups: UC-P (44 patients with dietary counselling and supplement with probiotics) and UC-NP (49 patients with dietary counselling, without supplement). Body composition was assessed using the multifrequency bioelectrical impedance device, and the quality of life related to UC was evaluated by applying the short inflammatory bowel disease questionnaire (SIBDQ). The results showed that the average value of muscular mass (MM) and sarcopenic index (SMI) significantly increased (p = 0.043, respectively, p = 0.001) and a large fraction (p = 0.001) of patients had their SMI levels normalized in the UC-P group compared with UC-NP group. The extracellular water to total body water ratio (ECW/TBW) also had significantly different mean values (p = 0.022), favoring the UC-P group. By testing the differences between the average values of body composition parameters before and after treatment, we obtained significant results in body mass index (BMI) (p = 0.046), fat free mass (FFM) (p < 0.001), and ECW/TBW ratio (p = 0.048). The SIBDQ total score increased significantly (p < 0.001) in the UC-P group and was more strongly associated with changes in body parameters. Supplementation with probiotics associated with L-glutamine and biotin can improve body composition parameters, which in turn implies an increase in the overall quality of life of patients with UC.

Crocin Ameliorates Diabetic Nephropathy through Regulating Metabolism, CYP4A11/PPARγ, and TGF-ß/Smad Pathways in Mice.

INTRODUCTION: Crocin is one of the main components of Crocus sativus L. and can alleviate oxidative stress and inflammation in diabetic nephropathy (DN). However, the specific mechanism by which crocin treats DN still needs to be further elucidated. METHOD: In the present study, a mouse model of DN was first established to investigate the therapeutic effect of crocin on DN mice. Subsequently, non-targeted metabolomics techniques were used to analyze the mechanisms of action of crocin in the treatment of DN. The effects of crocin on CYP4A11/PPARγ and TGF-ß/Smad pathway were also investigated. RESULT: Results showed that crocin exhibited significant therapeutic and anti-inflammatory, and anti-oxidative effects on DN mice. In addition, the non-targeted metabolomics results indicated that crocin treatment affected several metabolites in kidney. These metabolites were mainly associated with biotin metabolism, riboflavin metabolism, and arachidonic acid metabolism. Furthermore, crocin treatment upregulated the decreased levels of CYP4A11 and phosphorylated PPARγ, and reduced the increased levels of TGF-ß1 and phosphorylated Smad2/3 in the kidneys of DN mice. CONCLUSION: In conclusion, our study validated the considerable therapeutic, anti-inflammatory, and antioxidative impacts of crocin on DN mice. The mechanism of crocin treatment may be related to the regulation of biotin riboflavin and arachidonic acid metabolism, the activation of CYP4A11/PPARγ pathway, and the inhibition of TGF-ß/Smad pathway in the kidney.

Clinical, biochemical, and genetic analysis of 28 Chinese patients with holocarboxylase synthetase deficiency.

BACKGROUND: This study aimed to describe the clinical, biochemical, and molecular characteristics of Chinese patients with holocarboxylase synthetase (HLCS) deficiency, and to investigate the mutation spectrum of HCLS deficiency as well as their potential correlation with phenotype. METHODS: A total of 28 patients with HLCS deficiency were enrolled between 2006 and 2021. Clinical and laboratory data were reviewed retrospectively from medical records. RESULTS: Among the 28 patients, six patients underwent newborn screening, of which only one was missed. Therefore, 23 patients were diagnosed because of disease onset. Among all the patients, 24 showed varying degrees of symptoms such as rash, vomiting, seizures, and drowsiness, while only four cases remained asymptomatic nowadays. The concentration of 3-hydroxyisovalerylcarnitine (C5-OH) in blood and pyruvate, 3-hydroxypropionate, methylcitric acid, 3-hydroxyvaleric acid, 3-methylcrotonylglycine in urine were increased greatly among affected individuals. After prompt supplement of biotin, both the clinical and biochemical symptoms were dramatically resolved and nearly all patients developed normal intelligence and physique on follow-up. DNA sequencing revealed 12 known and 6 novel variants in the HLCS gene of patients. Among them, the variant of c.1522C > T was the most common. CONCLUSIONS: Our findings expanded the spectrum of phenotypes and genotypes for HLCS deficiency in Chinese populations and suggested that with timely biotin therapy, patients with HLCS deficiency showed low mortality and optimistic prognosis. Newborn screening is crucial for early diagnosis, treatment, and long-term outcomes.

Neuroimaging Features of Biotinidase Deficiency.

Biotinidase deficiency is an autosomal recessive condition caused by pathogenic variants in the BTD gene. Resultant deficiency of free biotin leads to impaired activity of the enzyme carboxylase and related neurologic, dermatologic, and ocular symptoms. Many of these are reversible on treatment, but early recognition and commencement of biotin supplementation are critical. This practice is especially important in countries where routine neonatal screening for biotinidase deficiency is not performed. In this report comprising 14 patients from multiple centers, we demonstrate the MR imaging patterns of this disorder at various age groups. Knowledge of these patterns in the appropriate clinical context will help guide early diagnosis of this treatable metabolic disorder.

Successful treatment with secukinumab of psoriasis-like dermatitis in a patient with holocarboxylase synthetase deficiency.

Holocarboxylase synthetase deficiency (HSD) is a rare autosomal recessive disorder of biotin metabolism. Typical manifestations include irreversible metabolic disorders and erythroderma-like dermatitis. Most patients respond well to biotin supplementation. Psoriasis-like phenotype associated with this disease has been rarely reported in the literature and experiences with the use of biologics in patients with HSD are still lacking. We reported a rare case of recurrent psoriasis-like skin lesions in a 6-year-old child with HSD. The patient did not respond to initial therapy with high-dose oral biotin. Immunofluorescence staining showed an increased number of interleukin (IL)-17A+ cells in his skin lesions. Based on this finding, the patient was successfully treated with human anti-IL-17A monoclonal antibody (secukinumab). He did not report any side effects and remained healthy during the 2-year follow-up. We provide a comprehensive review of the reported cases of HSD with psoriasis-like dermatitis to date. The psoriasis-like phenotype of HSD is controversial in treatment and IL-17A inhibitor is an alternative therapeutic option.

Probiotic supplement combined with topical therapy in the treatment of mild to moderate acne: results from an Italian single centre interventional study.

BACKGROUND: Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from different cofactors. The alteration of the skin microbiome has recently been revealed to play a role in acne pathogenesis. Concerns with side effects of available systemic treatment for acne resulted in a greater focus on topical therapies, such as topical azelaic acid which showed to be an effective and safe treatment option for acne. The aim of our study was to evaluate the efficacy of a new treatment protocol for acne based on an oral supplement composed of biotin and 3 strains of lactic ferments combined with a topical gel composed of azelaic acid, hydroxypinacolone retinoate, and α-hydroxy acids. METHODS: An Italian single-center interventional study was performed enrolling patients suffering from mild-to-moderate-acne. Patients were treated with a supplement based on biotin and 3 strains of lactic ferments, combined with a topical gel product (azelaic-acid, hydroxypinacolone retinoate, and α-hydroxy acids). All enrolled patients were scheduled for a total of 2 visits, a baseline visit (V0) and a follow-up visit after 60 days of treatment (V1). RESULTS: A total of 30 patients were enrolled in the study. Between V0 (baseline) and V1 (60 days), there was a reduction of 37.4% in the GAGS Score, 40.7% in the SEBUTAPEtm Score, and 18% in the TEWL Score, and an increment of 44% in the T-Blue Test Score. No cases of serious AEs were reported in our experience. CONCLUSIONS: Our results confirmed the promising therapeutic role of a probiotic supplement associated with topical therapy in the treatment of mild to moderate acne.

Beyond the caudate nucleus: Early atypical neuroimaging findings in biotin-thiamine- responsive basal ganglia disease.

BACKGROUND: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a treatable neurometabolic disease caused by variants in SLC19A3. Typical imaging features include symmetrical involvement of the caudate nuclei and putamina. OBJECTIVE: The study sought to explore classical BTBGD without caudate nucleus involvement, to highlight the importance of recognizing this new pattern early in the disease. METHODS: Individuals with genetically confirmed BTBGD who harbored the same homozygous variant: NM_025243.4 (SLC19A3): c.1264A > G (p.Thr422Ala) and had atypical neuroimaging were recruited. RESULTS: Nine patients with BTBGD had atypical neuroimaging findings on the first MRI scan. The median age at symptom onset was 3 years. All patients presented with classical clinical features of subacute encephalopathy, dystonia, ataxia, and seizures. During the acute crisis, MRI revealed bilateral and symmetric involvement of the putamina in all patients; one showed small caudate nuclei involvement. In addition, the thalami, cerebellum, and brain stem were involved in six patients, seven patients, and three patients, respectively. Treatment included a combination of high doses of thiamine and biotin. One patient died; he did not receive any vitamin supplementation. Two patients who were treated late had severe neurological sequelae, including generalized dystonia and quadriplegia. Six patients treated early had good outcomes with minimal sequelae, including mild dystonia and dysarthria. Two patients showed the classical chronic atrophic and necrotic changes already described. CONCLUSION: The early atypical neuroimaging pattern of BTBGD described here, particularly the lack of caudate nucleus involvement, should not dissuade the clinician and radiologist from considering a diagnosis of BTBGD.

Therapeutic Effects of a Novel Form of Biotin on Propionic Acid-Induced Autistic Features in Rats.

Magnesium biotinate (MgB) is a novel biotin complex with superior absorption and anti-inflammatory effects in the brain than D-Biotin. This study aimed to investigate the impact of different doses of MgB on social behavior deficits, learning and memory alteration, and inflammatory markers in propionic acid (PPA)-exposed rats. In this case, 35 Wistar rats (3 weeks old) were distributed into five groups: 1, Control; 2, PPA treated group; 3, PPA+MgBI (10 mg, HED); 4, PPA+MgBII (100 mg, HED); 5, PPA+MgBIII (500 mg, HED). PPA was given subcutaneously at 500 mg/kg/day for five days, followed by MgB for two weeks. PPA-exposed rats showed poor sociability and a high level of anxiety-like behaviors and cognitive impairments (p < 0.001). In a dose-dependent manner, behavioral and learning-memory disorders were significantly improved by MgB supplementation (p < 0.05). PPA decreased both the numbers and the sizes of Purkinje cells in the cerebellum. However, MgB administration increased the sizes and the densities of Purkinje cells. MgB improved the brain and serum Mg, biotin, serotonin, and dopamine concentrations, as well as antioxidant enzymes (CAT, SOD, GPx, and GSH) (p < 0.05). In addition, MgB treatment significantly regulated the neurotoxicity-related cytokines and neurotransmission-related markers. For instance, MgB significantly decreased the expression level of TNF-α, IL-6, IL-17, CCL-3, CCL-5, and CXCL-16 in the brain, compared to the control group (p < 0.05). These data demonstrate that MgB may ameliorate dysfunctions in social behavior, learning and memory and reduce the oxidative stress and inflammation indexes of the brain in a rat model.

Recovery of enzyme activity in biotinidase deficient individuals during early childhood.

Deficiency of the biotinidase (BTD) enzyme is an inborn error of biotin metabolism caused by biallelic pathogenic variants in the BTD gene. There are two forms, partial and profound BTD deficiency, which both can be successfully treated with pharmacological doses of biotin, justifying the inclusion of this disorder in the newborn screening in numerous countries. We investigated the BTD deficiency cohort (N = 87) in our metabolic center, as it was detected upon newborn screening since 2005, and aimed to better understand the long-term course of BTD enzyme activity and how it may relate to the patients' genetic background. We observed that individuals with partial BTD deficiency display an elevation of BTD enzyme activity with increasing age in 48% of cases-a recovery which allowed adjustment or stop of biotin supplementation in 20% of all individuals. In addition, we were able to recruit 56 patients (64%) for genetic testing, revealing 19 different variants (2 novel), and constituting 22 different genotypes. Genotype-phenotype correlations revealed that the most abundant allele in our cohort p.(Asp444His) was also the most common variant in patients displaying recovery of BTD enzyme activity. Based on our results, we recommend to retest all patients with partial BTD deficiency at the age of 5 years, as this may result in an impact on therapy. Moreover, genetic testing of BTD deficient individuals can allow prediction of the severity of BTD deficiency and of the likelihood of BTD enzyme activity recovery with age.

A survey-based study of physician practices regarding biotin supplementation.

Biotin is an important cofactor in several metabolic pathways in humans. Biotin deficiencies are quite uncommon and there is limited data to support recommending it to treat hair, skin, and nail conditions. A 2017 FDA safety alert warned that biotin can interfere with laboratory testing resulting in incorrect diagnoses and even death. Therefore, our study objectives were to assess biotin recommendation practices and survey physician knowledge of biotin interference in routine laboratory tests. In a national survey of 149 physicians, we found that 43.9% of physicians prescribe biotin, primarily for hair and nail disorders, and 39.5% recommended other biotin-containing supplements. Most physicians answered correctly that there are no randomized studies that biotin improves dermatological conditions, and that biotin interferes with thyroid and troponin testing. Few knew of interference with b-HCG, Hepatitis serology, HIV serology and Vitamin D levels, and 19.5% were unaware of any interference. Almost half of physicians did not ask patients to discontinue biotin prior to laboratory testing. Our study shows that physicians continue to prescribe biotin despite knowledge gaps about laboratory interference, and highlights the need for increasing physician awareness of risks and benefits of recommending biotin to treat skin, hair, and nail conditions.

High-dose biotin for multiple sclerosis: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND: Biotin may activate the acetyl-CoA-, 3-methylcrotonyl-CoA-, propionyl-CoA-, and pyruvate carboxylases to increase myelin repair and/or synthesis, and may enhance the production of adenosine triphosphate (ATP), which may be essential to prevent neurodegeneration. The purpose of this review was to determine the effectiveness and safety of high-dose biotin (HDB) in multiple sclerosis via a systematic review of randomized controlled trials. METHODS: We searched the following electronic databases for relevant articles: MEDLINE, CENTRAL, EMBASE, Scopus, and ClinicalTrials.gov website until April 2021. We considered randomized clinical trials (RCTs) that involved adult patients diagnosed with any phenotype of multiple sclerosis that conforms with the McDonald 2010/2017 criteria or the Lublin 2014 criteria. We included studies employing high-dose biotin or "MD1003" administered orally for at least 300 mg/day and given for at least three months. The methodological quality assessment of the included studies was done using the Cochrane Risk of Bias (RoB) tool. The GRADE approach was used to assess the certainty of evidence [COE]. RESULTS: Out of 366 records identified, three RCTs involving 889 individuals diagnosed with MS (830 participants had progressive MS (PMS); 59 had RRMS) were pooled for analyses. The overall female:male ratio was 1.16:1. All included trials used HDB as an adjunctive treatment. The risks of bias in the three studies were low across the domains. At 12 to 15 months, there is insufficient evidence that the HDB and placebo arms differed in terms of composite improvement of MS-related disability (relative risk (RR) 2.87; 95% CI 0.29-28.40; 2 trials; 796 participants; I2 = 66%) [low COE], improvement in expanded disability status scale (IEDSS) (RR 2.27; 95% CI 0.25-20.98; 2 trials; 796 participants; I2 = 63%) [low COE], and both IEDSS and improvement in 25-foot walk time (ITW25) (IEDSS-ITW25) (RR 0.58; 95% CI 0.17-2.00; 2 trials; 796 participants; I2 = 13%) [moderate COE] among patients with PMS. Pooled data for ITW25 at 12 to 15 months yielded statistical significance (RR 2.06; 95% CI 1.04-4.09; 2 trials; 796 participants; I2 = 0%) [moderate COE] favoring HDB among patients with PMS. At 12 to 15 months, no significant differences were found in terms of mean change in EDSS (MD -0.06; 95% CI -0.14-0.02; 2 studies; 796 participants; 889 participants; I2 = 68%) among patients with PMS. Synthesized data on incidence of any AEs (RR 0.98; 95% CI 0.92-1.04; 3 trials; I2 = 0%) [high COE] and any serious AEs (RR 0.98; 95% CI 0.77-1.24; 3 trials; 889 participants; I2 = 0%) [moderate COE] were not significantly different between HDB and placebo groups. Out of 662 pooled patients in the HDB group, 31 patients (4.7%) were found to have laboratory test interference compared to zero event in the pooled placebo group [high COE]. CONCLUSIONS: A moderate certainty of evidence suggests a potential benefit in favor of HDB administered for 12 to 15 months in terms of ITW25 in patients with PMS. However, an important trade-off of this benefit is the high certainty of evidence suggesting an increased incidence of laboratory test interference when HDB is taken.

Juvenile progressive optic atrophy as the presenting feature of biotinidase deficiency, a treatable metabolic disorder.

A 10-year-old girl initially diagnosed with functional visual loss was later diagnosed with progressive optic atrophy. Directed questioning at 13 years of age revealed difficulty hearing that had not been noted by the parents. Whole exome sequencing and subsequent metabolic testing confirmed biotinidase deficiency. Although biotinidase deficiency classically manifests in early childhood with multiple manifestations, such as seizures and failure to thrive, a delayed-onset form can present primarily as juvenile progressive optic atrophy. Early diagnosis is critical because biotin supplementation prevents disease and deterioration.

Dietary supplements in dermatology: A review of the evidence for zinc, biotin, vitamin D, nicotinamide, and Polypodium.

Dietary supplements are commonly recommended by dermatologists in the treatment of skin, hair, and nail disorders. This review of oral over-the-counter supplement use in dermatology summarizes current evidence for the use of zinc, biotin, vitamin D, nicotinamide, and Polypodium in the management of common dermatologic disorders. Evidence for the safety and efficacy of these supplements is limited. Very few large-scale randomized controlled trials exist for these over-the-counter supplements, particularly biotin and Polypodium. The lack of standardized dosing and standardized outcome measures makes comparison across existing studies challenging, and the lack of adverse events reporting in the majority of studies limits analysis of supplement safety. The most promising evidence exists for the use of nicotinamide in preventing nonmelanoma skin cancers. There is some evidence for the role of vitamin D in decreasing melanoma risk and progression in some individuals and for the photoprotective role of Polypodium, although additional high-quality studies are needed to determine appropriate dosing. Current evidence is insufficient to recommend the use of biotin or zinc supplements in dermatology. Large-scale randomized controlled trials investigating safety and efficacy are needed before widespread incorporation of these oral supplements into the general practice of dermatology.

Hair Loss After Sleeve Gastrectomy and Effect of Biotin Supplements.

Aim: In this study, we aimed to determine the incidence of hair loss in patients who underwent laparoscopic sleeve gastrectomy (LSG), and to observe whether use of Biotin has an impact on hair loss. Methods: This study included 156 female patients who underwent LSG for obesity and completed a 1-year follow-up. All patients with vitamin deficiency were screened in the pre- and postoperative period. Hair loss was defined as the subjective perception of the women of losing a higher amount of hair when compared with normal situation. Results: Hair loss was observed in 72% of the patients after LSG (n = 112). Seventy-nine percent of the patients reported hair loss between the third and fourth-month interval, and continued for an average of 5.5 ± 2.6 months. Permanent alopecia was not observed in any of the patients. Patients who experienced hair loss and Biotin deficiency after LSG were prescribed 1000 mcg/day of Biotin for 3 months. Of these 22 patients; only 5 (23%) patients reported a remarkable decline in hair loss. In addition, 29 patients were found to take 1000 mcg/day of Biotin for average 2.5 months after onset of hair loss by their own initiative, despite optimal blood Biotin levels. Eleven (38%) patients reported a remarkable decline in hair loss. The effect of biotin use on hair loss in patients with and without biotin deficiency was compared. There was no significant difference (P = .2). Conclusion: Temporary hair loss after LSG is common. It was found that biotin supplementation used to prevent hair loss does provide low efficacy.

Relapses in Patients Treated with High-Dose Biotin for Progressive Multiple Sclerosis.

High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (p = 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (p = 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.

Biomarkers of treatment response in patients with progressive multiple sclerosis treated with high-dose pharmaceutical-grade biotin (MD1003).

BACKGROUND: High-dose pharmaceutical-grade biotin (MD1003) has positive effects on disability in progressive multiple sclerosis (PMS), but its mechanism of action remains unclear. The objective of our study was to quantify the effect of MD1003 in patients with PMS, using clinical response, plasma neurofilament light chain (pNfL) levels, and brain (BV) or cervical spinal cord volume (CSCV). MATERIALS AND METHODS: Forty-eight patients with PMS newly treated with MD1003 were followed during one year. Patients were assessed clinically using the Expanded Disability Status Scale (EDSS), the nine-hole peg test (9HPT), and the 25-foot walk time (25FWT). CSCV was quantified using CORDIAL software and BV using SIENA or SIENAX. We measured pNfL level using SIMOA at several time points. Bayesian linear and logistic regressions were used to evaluate potential prognostic factors. RESULTS: Treatment response, defined as a significant decrease of EDSS, 25FWT, or 9HPT at 1 year, was observed in 13 patients (27%). A gain of volume was noted in 7/24 patients for brain and in 10/19 patients for cervical spinal cord. The strongest predictors of poor treatment response were a high pNfL level at MD1003 onset (OR 0.96; 95% CI [0.91; 1]), high age at MS onset (OR 0.95; 95% CI [0.89; 1.01]), and an increase in brain lesion load during MD1003 treatment (OR 0.81; 95% CI [0.55; 1.05]). CONCLUSIONS: MD1003 treatment was associated with clinical, BV, and CSCV improvement at 1 year. The correlation between the levels of pNfL at baseline, the age at multiple sclerosis onset, and a treatment response at M12 is consistent with a better effect in less disabled patients.