Рerformed: Mukashev S. Tursynkhanova A. Verified: Сourse: 4 Group: С.Д.Асфендияров атындағы Қазақ Ұлттық Медицина университеті Казахский Национальный Медицинский Университет имени С.Д.Асфендиярова

Recent studies have shown that a vitamin B deficiency in children occurs more often than previously assumed. A vitamin B12 deficiency in children often presents itself with non-specific symptoms such as developmental delays, a diverging growth curve, anorexia, irritability, neurological problems and weakness.In the event of a diverging growth curve in combination with neurological symptoms, or in combination with developmental delays, a vitamin B12 deficiency should be considered.

The amount of vitamin B12 during the first year of life is heavily dependent on how much vitamin B12 was available during the pregnancy and is therefore highly dependent on the vitamin B12 status of the mother. Typically, a newborn baby has a store of 25 ųg vitamin B12 in the liver, a quantity which is enough for the first year of life, even if the subsequent intake is insufficient. But this store is seriously reduced in mothers with a (untreated) vitamin B12 deficiency. This can already become apparent at the age of 3 to 4 months.

The serum B12 value decreases significantly after the birth. From the age of 6 months the value increases to a maximum between the age of 3 and 7, after which it slowly decreases to the adult value. This decrease continues throughout life, indicating that the current laboratory reference values should not be applied to children. Those reference values are based on healthy adults. The average value in children between the ages of 15 ½ and 19 years is around 369 pmol/L, which is considerably higher than the adult value. The folic acid level drops slowly until the age of 15, and from then corresponds with adult levels. Homocysteine levels increase with age, from an average of 5 ųmol/L in babies to 8.7 ųmol/L in the oldest group of children. From the age of 1 year the MMA remains at a stable low value (< 0.26 μmol/L).

Weakness Fatigue Lack of appetite Delay in growth Developmental delay or even regression Irritability Tingling or burning sensation (in extremities) Hypotonia (low muscle tone) Reduced tactile sensation Seizures Ataxia (lack of muscle control) Symptoms of paralysis Involuntary movements Concentration problems Memory disorders Personality changes Depression Macrocytosis Anaemia Hypersegmented neutrophils (type of white blood cells) Leukopenia (low white blood cell count) Thrombocytopenia (low blood platelet count) Glossitis Hyperpigmentation of the skin Vomiting Diarrhea and/or intestinal symptoms Jaundice Headache

The causes of a vitamin B12 deficiency in children can be divided into 3 categories: reduced intake malabsorption congenital errors in the transport & metabolism of vitamin B12.

Strictly vegetarian/vegan/macrobiotic diet Breastfeeding by a mother with an untreated vitamin B12 deficiency, or by a mother following one of the above diets Untreated phenylketonuria (a genetic condition)

Insufficient or no intrinsic factor due to: autoimmune pernicious anaemia, surgical removal of part of the intestine (bowel resection), absent/abnormal formation of intrinsic factor (hereditary) Reduced stomach acid, for example by long term treatment with acid reducing medications Reduced pancreatic function Competition in the intestines with vitamin B12 by parasites or bacterial overgrowth (SIBO) Malabsorption in the small intestine due to Crohns disease, celiac disease, small intestine surgery, or Imerslund-Gräsbeck syndrome

Disorder in the transport due to transcobalamin-II deficiency or cobalamin R- binder protein deficiency Metabolic disorders: adenosylcobalamin deficiency (cblA, cblB, mut), methylcobalamin deficiency (cblE, cblG), combined adenosylcobalamin and methylcobalamin deficiency (cblC, cblD, cblF, cblJ)

0 to 1 year: 326 – 591 pmol/L 2 to 5 years: 441 – 560 pmol/L 6 to 10 years: 345 – 438 pmol/L 11 to 14 years: 284 – 355 pmol/L 15 to 19 years: 216 – 272 pmol/L These values are from a survey of 234 children in the age group 0-19 years in Nijmegen (95 % CI). 2

The diagnosis should not be dependent on abnormal blood values. Macrocytosis for example is not specific to a vitamin B deficiency in children and also anaemia is not always present – as was previously assumed. It is estimated that if the values for haemoglobin, haematocrit and MCV are normal, more than 30% of vitamin B12 deficient patients will be missed. In patients with congenital metabolism disorders of vitamin B12, the serum B12 value is often normal because the vitamin B12 is present in the blood but not in the tissues. There can be a vitamin B deficiency in the tissues, even before the serum values are low.

Tests that can be done are: analysing the diet, testing for the presence of parasites, analysis of amino acids, transcobalamin levels, measuring the vitamin B12 binding capacity, tests for intrinsic factor antibodies and parietal cell antibodies.

The treatment depends on the cause of the deficiency. If the deficiency is mild and asymptomatic, a diet adjustment or the removal of the underlying cause plus a good supplement may be sufficient. In most cases however, the cause cannot be removed and permanent treatment with vitamin B12 injections will be necessary.

In the event of (serious) symptoms immediate treatment with vitamin B12 injections is necessary to prevent permanent damage. Children with metabolic disorders and lack of B12 binding proteins often require high doses of vitamin B12, as well as additional forms of treatment. In other literature 1 it is recommended that daily vitamin B12-injections (1000 μg) are administered for one week and then (possibly) to repeat every week during one month, followed by a maintenance dose. This advice is mainly empirically substantiated. For teenagers the adult treatment can be followed.

Folic acid deficiency anemia most commonly occurs in infants and results in a decrease in red blood cell production. Folic acid is required in high amounts in infants because it helps stimulate DNA replication and cellular growth. Infants who have a folic acid deficiency may show signs of chronic fatigue, dyspnea, heart palpitations, weakness, glossitis, nausea, low body weight, headache, fainting, irritability, pallor and jaundice, or a yellowing of the skin. Low folic acid intake during pregnancy and in the first stages of life can cause neural tube defects in infants. Neural tube defects are birth defects that affect the brain and spinal cord, the most common being spina bifida and anencephaly. Spina bifida occurs when the fetal spinal column does not close completely, causing nerve damage and lower-extremity paralysis. In anencephaly, much of the brain fails to develop, resulting in stillbirth or death shortly after birth.

Folic acid helps in the building of antibodies, which prevent and heal infections. It contributes to normal growth by aiding protein metabolism. It prevents premature graying of the hair and is essential for the health of hair and skin. It also produces nucleic acids that carry hereditary patterns and is necessary for the growth and division of all body cells.For a pregnant women and her developing foetus, folic acid is the single-most important nutrient and it ensures healthy pregnancy. Lactation is also improved by it.

Irritation is the most common symptom of folic acid deficiency. Folic acid or vitamin B9 is responsible for keeping the central nervous system healthy. So, due to its deficiency, depression and lethargy sets in. Lack of folic acid can also result in lightheadedness. It makes one forgetful even in a short span of time. There is a decrease in appetite and gradual loss of weight. Due to a lack of folic acid, there is a reduction of red bloods cells, which makes the skin appear pale. Concentrating and focusing is difficult. In pregnant women, the lack of folic acid can lead to abortion. The death rate is very high in infants whose mother suffers from folic acid deficiency. Since, the normal development of the spine and brain of the infant is aided by folic acid; its intake should be increased among pregnant women. In males, the lack of folic acid might lead to decrease in sperm count while in women it leads to the impairment of oocyte maturation.

Folic acid deficiency can also cause pain in the chest and abdomen, irregular heartbeat and shortness of breath. There is increase in hair fall and there is grayish-brown pigmentation of the skin. Slacking of mental agility. Lack of folic acid causes anemia because there is a decrease in the production of red blood cells, and diarrhea. Increase in the risk of schizophrenia. As folic, acid regulates the homocysteine levels, which increases due to the lack of folic acid. This increases the homocysteine level and it produces the cytokines responsible for triggering schizophrenia. There is a risk of increase in allergic diseases like asthma. Lack of folic acid in children can increase the risk of their contacting renal diseases.

Lack of diet that is rich in folic acid. Increase intake of alcohol. Dialysis of kidney. Low absorption of folic acid.

Folate is found in leafy green vegetables. Multi- vitamins also tend to include Folate as well as many other B vitamins. B vitamins, such as Folate, are water- soluble and excess is excreted in the urine.

When cooking, use of steaming, a food steamer, or a microwave oven can help keep more folate content in the cooked foods, thus helping to prevent folate deficiency. Folate deficiency during human pregnancy has been associated with an increased risk of infant neural tube defects. Such deficiency during the first four weeks of gestation can result in structural and developmental problems. NIH guidelines recommend oral B vitamin supplements to decrease these risks near the time of conception and during the first month of pregnancy.

Folate deficiency during gestation or infancy due to development by the fetus or infant of autoantibodies to the folate receptor might result in various developmental disorders including autism spectrum disorders. The role of vitamin B12and folate in depression is due to their role in transmethylation reactions, which are crucial for the formation of neurotransmitters (e.g. serotonin, epinephrine, nicotinamides, puri nes, phospholipids). The proposed mechanism, is that low levels of folate or vitamin B12 can disrupt transmethylation reaction, leading to an accumulation of homocysteine(hyperhomocisteinemia) and to impaired metabolism of neurotransmitters (especially the hydroxylation of dopamine and serotonin from tyrosine and tryptophan), phospholipids, myelin, and receptors. High homocysteine levels in the blood can lead to vascular injuries by oxidative mechanisms which can contribute to cerebral dysfunction. All of these can lead to the development of various disorders, including depression.