Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study.

BACKGROUND: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AIMS: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. METHODS: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. RESULTS: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. CONCLUSIONS: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement.

Importance: Neural tube defects are among the most common congenital malformations in the US, with an estimated 3000 pregnancies affected each year. Many of these neural tube defects are caused by low folate levels in the body. Objective: The US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update on the benefits and harms of folic acid supplementation. Population: Persons who are planning to or could become pregnant. Evidence Assessment: The USPSTF concludes that, for persons who are planning to or could become pregnant, there is high certainty that folic acid supplementation has a substantial net benefit to prevent neural tube defects in their offspring. Recommendation: The USPSTF recommends that all persons planning to or who could become pregnant take a daily supplement containing 0.4 to 0.8 mg (400 to 800 µg) of folic acid. (A recommendation).

Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

BACKGROUND: Prenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment. OBJECTIVES: To examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy. METHODS: We included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study. Information on ASM use, folic acid supplement use and dose, dietary folate intake, child autistic traits, and child language impairment was obtained from parent-reported questionnaires. Using logistic regression, we examined the interaction between prenatal ASM exposure and maternal genetic liability to folate deficiency expressed as polygenic risk score of low folate concentrations or maternal rs1801133 genotype (CC or CT/TT) on risk of language impairment or autistic traits. RESULTS: We included 96 children of women with ASM-treated epilepsy, 131 children of women with ASM-untreated epilepsy, and 37,249 children of women without epilepsy. The polygenic risk score of low folate concentrations did not interact with the ASM-associated risk of language impairment or autistic traits in ASM-exposed children of women with epilepsy compared with ASM-unexposed children aged 1.5-8 y. ASM-exposed children had increased risk of adverse neurodevelopment regardless of maternal rs1801133 genotype {adjusted odds ratio [aOR] for language impairment aged 8 y was 2.88 [95% confidence interval (CI): 1.00, 8.26] if CC and aOR 2.88 [95% CI: 1.10, 7.53] if CT/TT genotypes}. In children of women without epilepsy aged 3 y, those with maternal rs1801133 CT/TT compared with CC genotype had increased risk of language impairment (aOR: 1.18; 95% CI: 1.05, 1.34). CONCLUSIONS: In this cohort of pregnant women reporting widespread use of folic acid supplements, maternal genetic liability to folate deficiency did not significantly influence the ASM-associated risk of impaired neurodevelopment.

Combined action of SAMe, Folate, and Vitamin B12 in the treatment of mood disorders: a review.

Mood disorders affect more than 500 million people around the world. In the last decade, their prevalence has increased, and many people suffer from nervousness, anxiety, and stress at least once in their lives. The incidence of mood disorders and anxiety increases during perimenopause or under stressful conditions. The social restrictions introduced during the COVID-19 pandemic have significantly increased the normal burden of psychological and psychic disorders. In moderate to severe cases, pharmacological treatment is currently recommended, while in mild disorders, especially in the initial phase, psychological therapy is preferable. It is known that several nutrients are crucial for brain function. Among them, folate (vitamin B9), cyanocobalamin (vitamin B12), and S-adenosyl-L-methionine (SAMe) have been shown to influence various neurobiological processes. Overall, the available evidence suggests that dietary supplementation with folic acid, vitamin B12, and SAMe can be beneficial for people with mild mood disorders.

Folate Deficiency in an Urban Safety Net Population.

PURPOSE: Since mandatory fortification of grain products with folic acid in the United States in 1998, folate deficiency has become rare. Some have suggested that serum folate levels should be tested rarely in countries with mandatory folic acid fortification, given low rates of deficiency, high cost per deficiency diagnosis, and low rates of supplementation for those diagnosed as deficient. Given persistent racial, ethnic, and socioeconomic disparities in folate deficiency, these suggestions may not apply to all populations. We examine the rate at which serum testing detected folate deficiency in an urban safety net hospital and the characteristics of folate-deficient patients. METHODS: We reviewed the charts of all inpatients and emergency department patients with low serum folate results at a safety net hospital in Boston in 2018. We collected data concerning demographics, social determinants of health, clinical factors, and whether folate supplementation was prescribed. Finally, we performed a cost analysis. RESULTS: Of 1368 patients tested, 76 (5.5%) met criteria for folate deficiency. Overall, 86.8% of these patients were anemic, and 17.1% had macrocytic anemia; 42% were diagnosed with malnutrition. Common social determinants in folate-deficient patients included birth outside of the United States, homelessness, and alcohol use disorder. Of folate-deficient patients, 88% were newly prescribed folic acid supplementation at discharge. The estimated charge per deficient test was $1278. CONCLUSION: Compared with a nearby institution, serum folate testing at our safety net hospital detected deficiency at a higher rate, incurred a lower charge per deficient test, and was more likely to impact management.

The effects of folate and iron deficiency followed by supplementation on blood morphology and inflammation biomarkers in rats.

BACKGROUND: Little is known about the relation between iron and folic acid (FA) supplementation and inflammation. The aim of this study was to evaluate the effects of iron and folate deficiency and supplementation on blood morphology parameters, and to assess the role of iron and folate transporters in inflammation. METHODS: A four-week period of FA and iron deficiency in Wistar rats was followed by randomization into a group fed with a diet deficient in FA and supplemented with Fe (DFE), a group fed a diet deficient in Fe and supplemented with FA (DFOL), a group fed a diet supplemented with Fe and FA (FEFOL), a group fed a diet deficient in Fe and FA (D), and a group fed a control diet (C). The blood Crp concentration and blood count were determined. The expression of SLC11A2, SLC46A1, SLC19A1, and TFR2 proteins was assessed using the western blot method. RESULTS: After ten days on the experimental diets, the rats in the DFOL group had a 21% higher concentration of white blood cells (WBC) than the FEFOL group did (p < 0.05). We did not observe any differences between the groups in terms of C-reactive protein (Crp) concentration. We also did not find any other differences between the groups in other morphological parameters. Analysis of the correlation between blood count parameters and the expression of iron and folate transporters gave conflicting results. CONCLUSIONS: To conclude, iron and folate supplementation may affect WBC concentration in the blood.

Epidemiology and (Patho)Physiology of Folic Acid Supplement Use in Obese Women before and during Pregnancy.

Preconception folic acid supplement use is a well-known method of primary prevention of neural tube defects (NTDs). Obese women are at a higher risk for having a child with a NTD. As different international recommendations on folic acid supplement use for obese women before and during pregnancy exist, this narrative review provides an overview of epidemiology of folate deficiency in obese (pre)pregnant women, elaborates on potential mechanisms underlying folate deficiency, and discusses considerations for the usage of higher doses of folic acid supplements. Women with obesity more often suffer from an absolute folate deficiency, as they are less compliant to periconceptional folic acid supplement use recommendations. In addition, their dietary folate intake is limited due to an unbalanced diet (relative malnutrition). The association of obesity and NTDs also seems to be independent of folate intake, with studies suggesting an increased need of folate (relative deficiency) due to derangements involved in other pathways. The relative folate deficiency, as a result of an increased metabolic need for folate in obese women, can be due to: (1) low-grade chronic inflammation (2) insulin resistance, (3) inositol, and (4) dysbiotic gut microbiome, which plays a role in folate production and uptake. In all these pathways, the folate-dependent one-carbon metabolism is involved. In conclusion, scientific evidence of the involvement of several folate-related pathways implies to increase the recommended folic acid supplementation in obese women. However, the physiological uptake of synthetic folic acid is limited and side-effects of unmetabolized folic acid in mothers and offspring, in particular variations in epigenetic (re)programming with long-term health effects, cannot be excluded. Therefore, we emphasize on the urgent need for further research and preconception personalized counseling on folate status, lifestyle, and medical conditions.

Maternal folate levels during pregnancy and offspring brain development in late childhood.

BACKGROUND: Cumulative evidence shows that low maternal folate levels during pregnancy are associated with offspring neuropsychiatric disorders even in the absence of neural tube defects. However, the relationship between prenatal exposure to folate and brain development in late childhood has been rarely investigated. METHODS: In 2095 children from a prospective population-based cohort in Rotterdam, the Netherlands, we examined the association of maternal folate levels during pregnancy with downstream brain development in offspring. Maternal folate concentrations were measured from venous blood in early gestation. Child structural neuroimaging data were measured at age 9-11 years. In addition, measures of child head circumference using fetal ultrasound in the third trimester and total brain volume using magnetic resonance imaging at age 6-8 years were used for analyses with repeated assessments of brain development. RESULTS: Maternal folate deficiency (i.e., <7 nmol/L) during pregnancy was associated with smaller total brain volume (B = -18.7 cm3, 95% CI -37.2 to -0.2) and smaller cerebral white matter (B = -7.2 cm3, 95% CI -11.8 to -2.6) in children aged 9-11 years. No differences in cortical thickness or surface area were observed. Analysis of the repeated brain assessments showed that children exposed to deficient folate concentrations in utero had persistently smaller brains compared to controls from the third trimester to childhood (ß = -0.4, 95% CI -0.6 to -0.1). CONCLUSIONS: Low maternal folate levels during pregnancy are associated with altered offspring brain development in childhood, suggesting the importance of essential folate concentrations in early pregnancy.

[Chorioretinal atrophy in pediatric cerebral folate deficiency-a preventable disease?] / Chorioretinale Atrophie bei kindlichem zerebralem Folatmangel ­ eine vermeidbare Erkrankung?

Cerebral folate deficiency (CFD) results in neurological alterations and a massive degeneration of the choroid/retina if left untreated, which limit the visual field and visual acuity. This article reports the case of a female patient with CFD, who developed autistic personal characteristics prior to reaching school age and first started to speak at the age of 3 years. At the age of 6 years she was presented because of unclear reduced visual acuity in the right eye. At that time mild bilateral peripheral chorioretinal atrophy was present, which subsequently became more pronounced. Additionally, a centrally emphasized chorioretinal atrophy further developed. Visual acuity of both eyes progressively deteriorated until stagnating at 0.1 at the age of 14 years. The causal assignment of the findings of the patient was not possible for many years. Choroideremia was excluded by molecular genetic testing (CHM gene with no mutations) and gyrate atrophy was ruled out by a normal ornithine level. The existence of a mitochondrial disease was almost completely excluded by exome sequencing. After the onset of further nonocular symptoms, e.g. neuromuscular disorders, electroencephalograph (EEG) alterations and autistic disorder, intensified laboratory diagnostics were performed in the treating pediatric hospital. Finally, an extremely low level of the folic acid metabolite 5­methyltetrahydrofolate was detected in the cerebrospinal fluid (CSF) leading to the diagnosis of CFD. High-dose substitution treatment with folic acid was subsequently initiated. After excluding the presence of a pathogenic mutation of the FOLR1 gene for the cerebral folate receptor 1, a high titer blocking autoantibody against cerebral folate receptor 1 was detected as the cause.

Successful Treatment of Hereditary Folate Malabsorption With Intramuscular Folinic Acid.

BACKGROUND: Hereditary folate malabsorption is a multisystem disease owing to biallelic variants in the gene encoding the proton-coupled folate transporter. Hereditary folate malabsorption is treated with folinic acid, aimed to restore blood and cerebrospinal fluid folate levels. Little is known as to whether oral or intramuscular supplementation of folinic acid is most effective. METHODS: Here we describe a one-year-old boy with hereditary folate malabsorption presenting with the typical features including failure to thrive, aphthous stomatitis, macrocytic anemia along with severe developmental impairment and epilepsy, as well as a magnetic resonance imaging of the brain showing bilateral occipital, cortical calcifications characteristic of hereditary folate malabsorption. We compared the effect of treatment with oral folinic acid versus intramuscular folinic acid supplementation by measuring plasma and cerebrospinal fluid folate levels. RESULTS: Compared with oral administration, intramuscular treatment resulted in higher folate levels in blood and, most importantly, normalization of folate levels in cerebrospinal fluid. Clinically, nearly all systemic and neurological symptoms resolved. CONCLUSION: Normal cerebrospinal fluid folate levels can be achieved in individuals with hereditary folate malabsorption with intramuscular (but not with oral) administration of folinic acid.

An appraisal of folates as key factors in cognition and ageing-related diseases.

Folic acid (FA) is often consumed as a food supplement and can be found in fortified staple foods in various western countries. Even though FA supplementation during pregnancy is known to prevent severe congenital anomalies in the developing child (e.g., neural tube defects), much less is known about its influence on cognition and neurological functioning. In this review, we address the advances in this field and situate how folate intake during pregnancy, postnatal life, adulthood and in the elderly affects cognition. In addition, an association between folate status and ageing, dementia and other neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis is discussed. While its role in the incidence and severity of these diseases is becoming apparent, the underlying action of folates and related metabolites remains elusive. Finally, the potential of FA as a nutraceutical has been proposed, although the efficacy will highly depend on the interplay with other micronutrients, the disease stage and the duration of supplementation. Hence, the lack of consistent data urges for more animal studies and (pre)clinical trials in humans to ascertain a potential beneficial role for folates in the treatment or amelioration of cognitive decline and ageing-related disorders.

Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation.

BACKGROUND: For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. OBJECTIVE: The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. METHODS: We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. RESULTS: Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). CONCLUSIONS: The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.

Interventions to Improve Micronutrient Status of Women of Reproductive Age in Southeast Asia: A Narrative Review on What Works, What Might Work, and What Doesn't Work.

Objectives To provide an overview of nutrition-specific and nutrition-sensitive interventions that could improve micronutrient status of women of reproductive age. Methods This narrative review has a special focus on Southeast Asia, as the work was undertaken within the framework of the SMILING (Sustainable Micronutrient Interventions to controL deficiencies and Improve Nutrition status and General health in Southeast Asia) project. Results In order for new interventions to become accepted, comprehension and interpretation of potential impact of different strategies by policymakers and non-nutritionists is needed. By presenting a wide overview of strategies, and discussing the context and current consensus on these strategies, the review aims to help with the formulation of new recommendations for national programs in Southeast Asia. Conclusions Current policies in Southeast Asia to improve micronutrient status of women of reproductive age are focused too much on single micronutrient supplementation for pregnant women (iron and folic acid supplements). A more holistic approach, including both nutrition-specific and nutrition-sensitive interventions, is needed.

Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh.

Background: Arsenic exposure through drinking water persists in many regions. Inorganic As (InAs) is methylated to monomethyl-arsenical species (MMAs) and dimethyl-arsenical species (DMAs), facilitating urinary excretion. Arsenic methylation is dependent on one-carbon metabolism, which is influenced by nutritional factors such as folate and creatine. Objective: This study investigated the effects of folic acid (FA) and/or creatine supplementation on the proportion of As metabolites in urine. Design: In a 24-wk randomized, double-blinded, placebo-controlled trial, 622 participants were assigned to receive FA (400 or 800 µg per day), 3 g creatine per day, 400 µg FA + 3 g creatine per day, or placebo. The majority of participants were folate sufficient; all received As-removal water filters. From wk 12-24, half of the participants receiving FA received placebo. Results: Among groups receiving FA, the mean decrease in ln(%InAs) and %MMAs and increase in %DMAs exceeded those of the placebo group at wk 6 and 12 (P < 0.05). In the creatine group, the mean decrease in %MMAs exceeded that of the placebo group at wk 6 and 12 (P < 0.05); creatine supplementation did not affect change in %InAs or %DMAs. The decrease in %MMAs at wk 6 and 12 was larger in the 800 µg FA than in the 400 µg FA group (P = 0.034). There were no differences in treatment effects between the 400 µg FA and creatine + FA groups. Data suggest a rebound in As metabolite proportions after FA cessation; at wk 24, log(%InAs) and %DMAs were not significantly different than baseline levels among participants who discontinued FA supplementation. Conclusions: The results of this study confirm that FA supplementation rapidly and significantly increases methylation of InAs to DMAs. Further research is needed to understand the strong cross-sectional associations between urinary creatinine and As methylation in previous studies. This trial was registered at https://clinicaltrials.gov as NCT01050556.

Optic Nerve Degeneration and Reduced Contrast Sensitivity Due to Folic Acid Deficiency: A Behavioral and Electrophysiological Study in Rhesus Monkeys.

Purpose: The purpose of the research was to elucidate the role of folic acid (B9) deficiency in the development of nutritional optic neuritis and to characterize the neurophysiological consequences of optic nerve degeneration in the cortical visual system. Methods: A combined behavioral and electrophysiological approach was applied to study luminance contrast sensitivity in two macaque monkeys affected by nutritional optic neuritis and in two healthy monkeys for comparison. For one monkey, a follow-up approach was applied to compare visual performance before onset of optic neuropathy, during the disease, and after treatment. Results: Optic nerve degeneration developed as a consequence of insufficient dietary intake of folic acid in two exemplars of macaque monkeys. The degeneration resulted in markedly reduced luminance contrast sensitivity as assessed behaviorally. In one monkey, we also measured visual activity in response to varying contrast at the level of single neurons in the cortical visual system and found a striking reduction in contrast sensitivity, as well as a marked increase in the latency of neuronal responses. Prolonged daily folate supplementation resulted in a significant recovery of function. Conclusions: Folic acid deficiency per se can lead to the development of optic nerve degeneration in otherwise healthy adult animals. The optic nerve degeneration strongly affects contrast sensitivity and leads to a distinct reduction in the strength and velocity of the incoming signal to cortical visual areas of the macaque brain, without directly affecting excitability and functional properties of cortical neurons.

Can folate replacement induce lymphoma progression?

A 43-year-old Japanese man with a low haemoglobin level of 1.3 g/dL and multiorgan dysfunction syndrome (MODS) was admitted to our hospital. He was diagnosed with folate deficiency, which was initially attributed to his malnutrition. He was transfused with several units of packed red blood cells and treated with folate, thiamine and vitamin B12 supplements; he showed a prompt haematological response and recovery from MODS. However, 3 weeks after the initial recovery, he had a relapse of pancytopenia and developed high-grade fever along with rapidly enlarging, generalised lymphadenopathy. Bone marrow biopsy revealed hemophagocytosis, and lymph node biopsy revealed peripheral T-cell lymphoma, not otherwise specified. Folate supplementation may have promoted lymphoma progression.

Acid folic and pregnancy: A mandatory supplementation.

Neural tube defects (NTD) occur in 0.5 to 2 per 1000 pregnancies with various handicaps for the affected child. It is now well established that folic acid deficiency (absolute or relative) is a predisposing factor to this type of malformation. Several randomized controlled trials showed that high-dose folic acid (4mg) is an essential factor for prevention of neural tube defects recurrence and significantly prevents the first occurrence of neural tube defects with a lower dose (0.4mg). Other etiologies can favor the occurrence of NTD such as MTHFR polymorphism, some antiepileptic therapies, obesity and pregestational mellitus diabetes. Necessity of a preconception folic acid supplementation or at least folate nutritional status evaluation should be known for all of us including patients and public.

Diet and fertility: a review.

The literature on the relationship between diet and human fertility has greatly expanded over the last decade, resulting in the identification of a few clear patterns. Intake of supplemental folic acid, particularly at doses higher than those recommended for the prevention of neural tube defects, has been consistently related to lower frequency of infertility, lower risk of pregnancy loss, and greater success in infertility treatment. On the other hand and despite promising evidence from animal models, vitamin D does not appear to exert an important role in human fertility in the absence of deficiency. Antioxidant supplementation does not appear to offer any benefits to women undergoing infertility treatment, but it appears to be beneficial when it is the male partner who is supplemented. However, the available evidence does not allow discerning which specific antioxidants, or at which doses, are responsible for this benefit. Long-chain omega-3 fatty acids appear to improve female fertility, although it remains unclear to what extent contamination of shared food sources, such as fish with high levels of environmental toxicants, can dampen this benefit. Lastly, adherence to healthy diets favoring seafood, poultry, whole grains, fruits, and vegetables are related to better fertility in women and better semen quality in men. The cumulative evidence has also piled against popular hypotheses. Dairy and soy, once proposed as reproductive toxicants, have not been consistently related to poor fertility. In fact, soy and soy supplements appear to exert a beneficial effect among women undergoing infertility treatment. Similarly, because data from large, high-quality studies continue to accumulate, the evidence of a potentially deleterious effect of moderate alcohol and caffeine intake on the ability to become pregnant seems less solid than it once did. While a complete picture of the role of nutrition on fertility is far from complete, much progress has been made. The most salient gaps in the current evidence include jointly considering female and male diets and testing the most consistent findings in randomized trials.

Folate deficiency in patients with classical galactosemia: A novel finding that needs to be considered for dietary treatments.

Çelik M, Özgün N, Akdeniz O, Fidan M, Tüzün H, Ipek MS, Emecan M, Eminoglu FT. Folate deficiency in patients with classical galactosemia: A novel finding that needs to be considered for dietary treatments. Turk J Pediatr 2018; 60: 540-546. The objectives of the study were to assess folate deficiency in patients with classic galactosemia, and to determine whether folic acid supplementation has an effect on galactose-1-phosphate uridyltransferase enzyme activity. Sixty-one newborn infants diagnosed with classic galactosemia between 2010 and 2017 were retrospectively evaluated. Within this group, 48 patients with Q188R homozygous mutation alone were enrolled into the study. Serum folate concentration was studied using chemiluminescence; and in folate deficient patients, galactose-1-phosphate uridyltransferase measurements before and after folic acid supplementation (100 mg/day folic acid for 30 days) were performed using an enzymatic calorimetric measurement technique based on kinetics. The serum folate level was low ( < 4 ng/ml) in 12 patients (25%). The galactose-1-phosphate uridyltransferase enzyme activity after folic acid supplementation was significantly higher than the values before folic acid supplementation (1.00±0.19 U/g Hb vs. 0.74±0.23 U/g Hb, p < 0.05); but was still less than the normal levels. Folate deficiency, most likely due to poor dietary intake, may develop in pediatric patients with classical galactosemia, and folic acid should be supplemented. Folic acid supplementation appears to have a low, but statistically significant, effect on galactose-1-phosphate uridyltransferase enzyme activity, but comprehensive research is needed to clarify whether there is any clinical significance.

Hereditary folate malabsorption with a novel mutation on SLC46A1: A case report.

RATIONALE: Hereditary folate malabsorption (HFM) is characterized by folate deficiency with impaired intestinal folate absorption and impaired folate transport into the central nervous system. Its manifestations mainly include macrocytic anemia, recurrent infections, and neurological deficits. The neurological manifestations include progressive psychomotor retardation, behavioral disorders, and early-onset seizures. PATIENT CONCERNS: From early infancy, a Chinese boy had experienced macrocytic anemia, leukopenia, thrombocytopenia, recurrent pneumonia, diarrhea, and mouth ulcers. He also presented with progressive neurological symptoms. DIAGNOSIS: A novel mutation in the SLC46A1 gene was identified, and HFM was diagnosed at 18 months of age. INTERVENTIONS: After the HFM diagnosis, the boy was treated with folinic acid. LESSONS: Folinic acid supplementation is effective and may offer life-changing therapy for patients with HFM.