Evaluation of Clinical and Laboratory Findings of Children with Vitamin B12 Deficiency

Objective: Vitamin B12 deficiency causes significant neurological, hematological and gastrointestinal system problems in children. Many systemic problems can be prevented with early recognition and treatment of Vitamin B12 deficiency, which is an important public health problem in all over the world. We aimed to evaluate children who applied to pediatric health and diseases outpatient clinics and were found to have vitamin B12 deficiency. Materials and Methods: Children aged 0-18 years who were admitted to the Education and Research Hospital Pediatrics outpatient clinics for any reason and were found to have vitamin B12 deficiency were evaluated retrospectively. Age, gender, admission complaints, serum vitamin B12 levels, leukocyte in complete blood count, hemoglobin (Hb), mean erythrocyte volume (MCV), platelet values, ferritin, thyroid function tests (TSH and fT4) were evaluated. Findings: A total of 137 (60.6%) of the 226 cases that were included in our study were girls, and 89 (39.4%) were boys. The mean age of the cases was 10±7.6 years. Macrocytosis was not observed in cases with anemia. Iron deficiency was present together with Vitamin B12 deficiency in 26 (11%) of the cases. Iron deficiency was detected together with Vitamin B12 deficiency in 18 (8%) of the cases diagnosed with anemia. In our study, anemia was found in 18.2% of the cases, neutropenia in 8.4%, and thrombocytopenia in 0.8%. The most common complaints were fatigue and loss of appetite (24.8%), growth retardation (short stature, inability to gain weight) (13.7%), chest pain, syncope and palpitations (8.4%). Results: We think that it would be appropriate to evaluate vitamin B12 levels in children with undiagnosed neurological, respiratory, gastrointestinal or cardiac complaints who were admitted to pediatric outpatient clinics.


Introduction
Vitamin B12 is a water-soluble vitamin and is obtained from animal products, such as red meat, dairy products, and eggs. The intrinsic factor is a glycoprotein that is produced by parietal cells in the stomach and is essential for the absorption of Vitamin B12 in the terminal ileum. After Vitamin B12 is absorbed, it is used as a cofactor for the enzymes, which play roles in the synthesis of the DNA, fatty acids, and myelin. Inadequate intake of it with diet, intestinal absorption disorders, and autoimmune metabolic diseases cause Vitamin B12 deficiency [1].
The purpose of the present study was to evaluate children between 0-18 years of age who admitted to children's health and diseases clinics for various reasons, and who have Vitamin B12 deficiency.

Material and Method
Patients admitting to Ordu University, Educational Research Hospital, Children's Health and Diseases Clinics for any reason, and who were detected to have Vitamin B12 deficiency were evaluated retrospectively in the present study.
Serum Vitamin B12 levels below 200 pg/mL were considered to be low values (1). Patients between the ages of 0-18 who admitted between the dates January 2020 and November 2020, and who had Vitamin B12 deficiency were examined retrospectively. f.

Discussion
Vitamin B12 deficiency is more common in developing countries. The prevalence varies between 3-40% in children in the world [8,9].
Although it is known that Vitamin B12 deficiency causes macrocytary anemia, no macrocytosis was detected in patients with anemia in our study. Iron deficiency was detected together with Vitamin B12 deficiency in 18 (8%) of the cases with anemia.
The percentage of microcytic anemia was significantly higher and hemoglobin value was significantly lower in anemia cases that had iron and Vitamin B12 deficiency detected together than anemias with Vitamin B12 deficiency alone (p<0.05). MCV may be detected as low or normal in patients with iron deficiency together with Vitamin B12 deficiency. Iron deficiency anemia is common in our country. For this reason, the diagnostic interpretation of MCV may cause misevaluation of cases. It was reported in the literature that iron deficiency masks macrocytosis in macrocytary anemia [10,11].
The diagnosis of Vitamin B12 deficiency cannot be excluded when anemia and/or macrocytosis are not present [12]. In our study, 18.2% of cases had anemia, 8.4% had neutropenia, and 0.8% had thrombocytopenia. There are studies in the literature reporting that there were no significant differences when children with and without Vitamin B12 deficiency were compared in terms of leukocyte, neutrophil, hemoglobin, MCV and platelet values [13].
Despite Vitamin B12 deficiency in our cases, the parameters that were examined in full blood counts were mostly normal, which shows that hematological parameters alone cannot guide diagnostic evaluation [13].
The admission complaints of individuals with Vitamin B12 deficiency vary among age groups. Patients may be asymptomatic or may be diagnosed with significant life-threatening hematological and neurological diseases [4][5][6]9].
neurological symptoms, respectively. Again in the same study, it was also reported that neurological symptoms were more significant in patients who were under 2 years of age [14]. Studies were reported in the literature supporting more significant neurological symptoms at the first 2 years of age [15][16][17]. The most common complaint was reported as faintness in another study in which 82% of cases were under two years of age [18].
In the present study, the most common admission complains were weakness and loss of appetite (24.8%), growth deficiency (short stature and inability to gain weight) (13.7%), chest pain, syncope and palpitation (8.4%).
Although the mechanism of neurological symptoms in Vitamin B12 deficiency is not known completely, delayed myelination, neurotrophic and neurotoxic cytokine and lactate accumulation in the brain cells were argued to be the causes [19].
When all these findings are evaluated together, Vitamin B12 deficiency shows itself with non-specific admission complaints, clinical findings, and laboratory data in childhood.
The retrospective design of the present study, the inability to access the anthropometric data and dietary status of the cases in detail were important limitations. Also, the lack of examining the most original and specific marker of Vitamin B12 deficiency with urine/serum methyl malonic acid level was not another limitation.
Wider prospective studies covering admission complaints, clinical findings and laboratory data according to age groups will ensure that Vitamin B12 deficiency is noticed earlier. In this way, preventable life-threatening problems can be prevented.

1.
Children with Vitamin B12 deficiency most often admitted with fatigue, loss of appetite, and growth deficiency.

2.
Anemia was detected only in 18.2% of patients who had Vitamin B12 deficiency, and macrocytosis was not detected in patients with anemia. 3.