BACKGROUND: 17-Hydroxylase deficiency is the rarest form of congenital adrenal hyperplasia, a disorder that affects steroidogenesis, causing abnormal hormone levels. Studies have shown a clear association between 17-hydroxylase deficiency and primary infertility, but a definite protocol to treat the disorder has not been determined yet.
METHODS: Case I presents a 24-year-old Caucasian Israeli-Arab female who experienced 6 years of infertility. Before her initial visit to our clinic, she underwent three laparoscopic ovarian cystectomies, had an unsuccessful in vitro fertilization cycle, and was treated with combined oral contraceptives. Her hormonal profile was tested, and the results led to genetic counseling and the diagnosis of non-classical congenital adrenal hyperplasia. She was treated with estradiol, glucocorticoids, and transdermal testosterone. After hormonal levels were lowered, in vitro fertilization cycles were initiated, and the patient had a spontaneous ovulation. In case II, a 20-year-old Caucasian Israeli-Arab female presented for infertility evaluation owing to her oligomenorrhea. Her vitals and physical examination had normal results. The investigation of her abnormal hormonal profile led her to be referred to genetic testing, where the results showed the same genetic mutation as seen in case I.
CONCLUSIONS: Both cases highlight the distinctiveness of the condition, where an identical mutation in the gene responsible for the same enzyme can bring about diverse phenotypes. Case I offers a potential treatment protocol for this rare disorder.

Adequate vitamin D (VD) intake during pregnancy is needed for fetal development and maternal health maintenance. However, while there is no doubt regarding its importance, there is not a unified recommendation regarding adequate intake. The main aim of our study was to measure the VD serum level of studied women, together with its potential influencing factors: demographic (i.e., age, level of education, relationship status and type of residence), conception and pregnancy related factors. Results are based on secondary data analyses of a retrospective case-control study of 100 preterm and 200 term pregnancies, where case and control groups were analyzed together. Data collection was based on a self-administered questionnaire, health documentation, and maternal serum VD laboratory tests. VD intake was evaluated by diet and dietary supplement consumption. According to our results, 68.1% of women took some kind of prenatal vitamin, and only 25.9% of them knew about its VD content. Only 12.1% of included women reached the optimal, 75 nmol/L serum VD level. Higher maternal serum levels were associated with early pregnancy care visits (p = 0.001), assisted reproductive therapy (p = 0.028) and advice from gynecologists (p = 0.049). A correlation was found between VD intake and serum levels (p < 0.001). Despite the compulsory pregnancy counselling in Hungary, health consciousness, VD intake and serum levels remain below the recommendations. The role of healthcare professionals is crucial during pregnancy regarding micronutrients intake and the appropriate supplementation dose.

Carbonic anhydrase II deficiency is an extremely rare inborn error of metabolism that constitutes a triad osteopetrosis, renal tubular acidosis and intracerebral calcification. Unlike other subtypes of osteopetrosis, the presence of developmental delay and relative infrequency of skeletal fractures may not be a typical signs of symptoms indolent trajectory. This case report demonstrates a 11-year-old boy who had a bilateral midshaft tibial fracture despite low mechanism of injury. He was found to have severe respiratory distress with hypokalemia shortly after arriving to the emergency department venous blood gas (VBG) showed moderate metabolic acidosis. Potassium was corrected but he persistently had low potassium level despite frequent corrections. He was then started on sodium bicarbonate boluses. Whole exome sequencing (WES) was sent, and result was consistent with autosomal recessive osteopetrosis type III with renal tubular acidosis (RTA) evident by pathologic variant on CA2 gene confirming the diagnosis of carbonic anhydrase II (CA II) deficiency consistent with the unique Arabic mutation. Conversely, low mechanism of fracture injury in the context of severe form of fracture type should raise the concern of (CA II) deficiency especially in a pediatric patient who show no signs of developmental of cognitive delay.

Plasminogen deficiency, a rare disorder characterized by impaired fibrinolysis, frequently results in ligneous conjunctivitis. In this report, we report a case of a Saudi girl manifesting both conjunctivitis and hydrocephalus. Her initial symptoms at 1 month of age were recurring eye redness, which was inaccurately diagnosed as simple conjunctivitis. Surgical intervention for her ocular lesions revealed underlying membrane deposition. She later exhibited signs of increased intracranial pressure, resulting in a hydrocephalus diagnosis and subsequent surgery. Genetic analysis confirmed the presence of plasminogen deficiency. Clinical evaluations highlighted ligneous conjunctivitis, variations in visual acuity, and facial acne. Laboratory assessments demonstrated diminished plasminogen levels. The therapeutic approach encompassed plasminogen replacement, administered intravenously (1000 units, thrice weekly) and as eye drops, with the potential addition of fresh frozen plasma. Notably, this replacement therapy led to a significant reduction in hospital admissions and the severity of her conjunctivitis. Given the challenges in procuring consistent plasminogen supplies, the viability of hepatic transplantation is currently under investigation.

BACKGROUND: Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, characterized by impaired epidermal barrier function and an altered immune response, both of which are influenced by vitamin D deficiency. Single-nucleotide polymorphisms (SNPs) in VDR and CYP24A1 have been previously associated with AD.
OBJECTIVE: We sought to characterize the associations between the VDR and CYP24A1 polymorphisms and the vitamin D and lipid biochemical profile in children diagnosed with AD.
METHODS: A total of 246 participants (143 patients with AD and 103 healthy controls) were enrolled in this study. Genotyping for polymorphisms in VDR (rs2239185, rs1544410, rs7975232, rs2238136, rs3782905, rs2239179, rs1540339, rs2107301, rs2239182, and rs731236) and CYP24A1 (rs2248359 and rs2296241) was performed by allele-specific polymerase chain reaction using integrated fluidic circuit technology. Serum levels of calcium, phosphorus, and vitamin D were measured, and the biochemical lipid profile was determined.
RESULTS: Among VDR SNPs, rs2239182 exerted a protective effect against the development of AD, whereas rs2238136 was identified as a risk factor for AD. The GCC haplotype (rs2239185-G, rs1540339-C, and rs2238136-C) appeared to protect against the development of AD. rs2239182-CC was associated with higher 25(OH)D concentrations, whereas rs2238136-TT, rs2239185-GA, and rs2248359-TT were present in a large proportion of patients with serum vitamin D deficiency. rs2239185-AA, rs2239182-CC, and rs1540339-CC were associated with higher serum total cholesterol; rs2239182-TT was associated with lower low-density lipoprotein cholesterol; and rs2239182-TC with lower high-density lipoprotein cholesterol. Both CYP24A1 SNPs (rs2296241-AA and rs2248359-TT) were associated with higher high-density lipoprotein cholesterol levels.
CONCLUSIONS: The VDR SNP rs2238136 is a risk factor for AD and other SNPs in VDR and CYP24A1, which may lead to alterations in biochemical parameters that influence the risk of AD. Our findings highlight the complex genetic basis to AD and indicate that interrelationships between different genetic factors can lead to alterations in vitamin D metabolism or lipid profiles, which in turn may influence the development of AD.

UNASSIGNED: Thyroxine binding globulin (TBG) deficiency is a rare thyroid disease, mostly caused by genetic mutations and acquired by X-linked recessive inheritance. The clinical features of children with TBG deficiency and their family members were summarised and the Serpina7 gene mutation was analysed, providing a reference for the differentiation of TBG deficiency.
UNASSIGNED: Thyroid function was detected in TBG deficient patients, and genetic analysis was performed using polymerase chain reaction (PCR) and direct DNA sequencing to detect the characteristics of TBG mutants. Using \"thyroxine binding globulin, gene and mutation\" as keywords, PubMed (biomedical literature database), Web of Science and other databases were searched for relevant studies to collect and summarise relevant information.
UNASSIGNED: The TBG (14.7 μg/mL), 70% triiodothyronine (T3) (<0.3 nmol/L), total T3 (Tr3) (<0.05 ng/mL) and thyroxine (T4) (14.72 nmol/L) values were lower than normal, while the thyrotropin (TSH) (2.33 uIU/mL), free T3 (FT3) (1.62 pmol/L), and free T4 (FT4) (11.39 pmol/L) values were normal. These values indicate a TBG partially deficient phenotype. Using PCR amplification and direct sequencing of the target gene, a missense mutation in exon 4 of the Serpina7 gene was found in the patient and the father, and the nucleic acid variant was C.909 (exon 4) g > T; the patient was heterozygous and the father was hemizygous. The literature search retrieved a total of 45 studies, most of which were related to mutations in the Serpina7 gene. The mutation locations included exons, introns, enhancers and promoters, with exons the predominant location. A total of 49 variants of the Serpina7 gene were identified.
UNASSIGNED: Serpina7 C.909G (P.L303F) is a mutation acquired from the father by X-linked recessive inheritance. The main clinical features of TBG deficiency patients are low serum T4, T3 and TBG levels, normal TSH, FT3 and FT4 levels, and no clinical manifestations.

UNASSIGNED: Depression is a global burden with complex etiopathogenesis. Some nutrients including vitamin D, B12, and folate deficiency have been considered risk factors for depression. Therefore, this study has been contemplated to find out the possible association of vitamin D, B12, and folate deficiency with depression.
UNASSIGNED: This study included 81 case subjects with depression and 95 control subjects without any International Classification of Diseases (ICD)-10 diagnosis. The sociodemographic details were collected from each subject. Beck\'s Depression Inventory (BDI) was administered to identify the severity of depression. The blood samples were collected and measured for vitamin D, B12, and folate along with other laboratory investigations as per exclusion criteria. The data were obtained and analyzed using descriptive and inferential statistics.
UNASSIGNED: The mean age ± standard deviation (SD) of the case and control subjects were 34.86 ± 9.25 and 33.49 ± 8.44, respectively, without any significant difference (P > 0.05). The subjects with vitamin D deficiency were found to have four times higher odds (OR 4.703; 95% CI = 2.378-9.300) for depression compared to subjects with sufficient vitamin D levels. In addition, there was a negative correlation between vitamin D levels and the severity of depression as per BDI scoring (r = -.384, P < 0.01). However, there was no significant association identified between the case and control group with respect to serum vitamin B12 and folate levels.
UNASSIGNED: The results of the study revealed that vitamin D deficiency has an association with depression. However, further research studies are needed to validate its correlation to the etiopathogenesis of depression.

Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data.
Case-control study comparing the first PCR-confirmed COVID-19 symptomatic cases in the Vaud Canton (May to June 2020, n = 199) and controls (random population sample, n = 447), seronegative for IgG and IgA. The replication analysis included seropositive (n = 134) and seronegative (n = 152) close contacts from confirmed COVID-19 cases. Anti-SARS-CoV-2 IgG and IgA levels against the native trimeric spike protein were measured using the Luminex immunoassay. We measured plasma Zn, Se and Cu concentrations by ICP-MS, and 25-hydroxy-vitamin D3 (25(OH)D3) with LC-MS/MS and explored associations using multiple logistic regression.
The 932 participants (54.1% women) were aged 48.6 ± 20.2 years (±SD), BMI 25.0 ± 4.7 kg/m2 with median C-Reactive Protein 1 mg/l. In logistic regressions, log2(Zn) plasma levels were negatively associated with IgG seropositivity (OR [95% CI]: 0.196 [0.0831; 0.465], P < 0.001; replication analyses: 0.294 [0.0893; 0.968], P < 0.05). Results were similar for IgA. We found no association of Cu, Se, and 25(OH)D3 with anti-SARS-CoV-2 IgG or IgA seropositivity.
Low plasma Zn levels were associated with higher anti-SARS-CoV-2 IgG and IgA seropositivity in a Swiss population when the initial viral variant was circulating, and no vaccination available. These results suggest that adequate Zn status may play an important role in protecting the general population against SARS-CoV-2 infection.
CORONA IMMUNITAS:: ISRCTN18181860.

BACKGROUND: Vitamin D is an essential component in calcium metabolism. Seasonality, advanced age, sex, dark skin pigmentation, and limited exposure to sunlight were reported as causes of vitamin D deficiency. This study aims to determine whether children with lower levels of vitamin D suffer more fractures than those with sufficient levels.
METHODS: Our institution underwent a prospective case-control randomized cross-sectional single-blinded study that included 688 children. They were split into two groups: the study group and the control group. The study group received supplements of vitamin D and calcium for 6 months. Another reference cohort was observed, which comprised 889 patients in the pediatric ward for different respiratory or gastroenterological conditions without a history of fractures. This group was used for age-sex matching tests.
RESULTS: Logistic regression showed that with every one unit increase of vitamin D level, the chance of having a middle third fracture in both bones of the forearm decreased by 7% (OR 1.07); distal third fracture incidence decreased by 1.03 times; middle third radius fracture incidence decreased by 1.03 times; distal third radius fracture incidence decreased by 1.06 times. The risk of having a distal third both-bone forearm fracture increased by 1.06 times with every year of age. Comparing the healing process, we noticed an improvement in bony callus formation for patients in the study group.
CONCLUSIONS: Dosing the serum level of 25-OH-vitamin D should be taken into consideration for pediatric low-energy trauma fractures. Supplementing with vitamin D and calcium throughout childhood can be a solution for healthy bones. Our preliminary results show that the normal level of vitamin D in children should start at 40 ng/mL.

The relationship between non-communicable diseases and eating behaviour has long been attributed to a surplus of food and energy. However, the increase in the prevalence of non-communicable disease and their underlying low-grade inflammatory milieu among people of low socio-economic status has highlighted the existence of a confounding factor. In this work, we aim to study the effect of lysine deficiency on some inflammatory markers in the absence or presence of an inflammatory insult (lipopolysaccharide (LPS)). For this purpose, thirty-two 5-week-old male Sprague Dawley rats were randomly distributed into four groups: (1) control diet, (2) control diet+LPS, (3) lysine-deficient diet and (4) lysine-deficient diet + LPS. Groups were only allowed their experimental diets for 4 weeks, during which LPS (50 µg/kg) or saline injections were administered intraperitoneally three times per week. The study showed that lysine deficiency blunted growth and body compartments development, decreased albumin production and elevated liver C-reactive protein (CRP) expression, independently of IL-6 and IL-1β, the main precursors of CRP. Also, the insufficient levels of lysine in the diet increased hyperactivity and triggered an anxiety-like behaviour, exacerbated with LPS. This work presents evidence that various physiological changes are associated with the absence of a sufficient amount of lysine in the diet and can potentially increase the risk factor for diseases. Thus, the increment in non-communicable disease among the low socio-economic status populations, who heavily rely on cereals as a main source of protein, can be, at least partially, blamed on low lysine availability in diets.