The amount of vitamin D recommended for all infants, children, and adolescents has recently increased – from 400 to 600 IU per day. The National Academy of Medicine (NAM) released the Consensus Report on Dietary Reference Intakes for Calcium and Vitamin D on November 30, 2010. The recommendation was for 600 IU of vitamin D a day for those 1–70 and 800 IU for those over 70 years of age. As of October 2008, the American Pediatric Association advises vitamin D supplementation of 400 IU/day (10 μg/d) from birth onwards. (1 IU vitamin D is the biological equivalent of 0.025 μg cholecalciferol/ergocalciferol.) The daily dose of 400 IU is required to prevent rickets and possibly also a wide range of chronic nonskeletal diseases. The Canadian Paediatric Society recommends that pregnant or breastfeeding women consider taking 2000 IU/day, that all babies who are exclusively breastfed receive a supplement of 400 IU/day, and that babies living north of 55°N get 800 IU/day from October to April. Infant formula is generally fortified with vitamin D. Hypovitaminosis D is common in postmenopausal women, regardless of whether they are healthy or have other medical conditions.

The replacement of vitamin D needs for treating Vitamin D deficiency depends on the severity of the deficiency. Treatment involves an initial high-dosage treatment phase until the required serum levels are reached, followed by the maintenance of the acquired levels. The lower the 25(OH)D serum concentration is before treatment, the higher is the dosage that is needed in order to quickly reach an acceptable serum level.

The initial high-dosage treatment can be given on a daily or weekly basis or can be given in form of one or several single doses (also known as "stoss therapy", from the German word "Stoß" meaning "push").

Therapy prescriptions vary, and there is no consensus yet on how best to arrive at an optimum serum level. While per mole vitamin D is more potent to raise 25(OH)D blood levels than vitamin D, per IU both D and D are equal for maintaining 25(OH)D status.

The official recommendation from the United States Preventive Services Task Force is that for persons that do not fall within an at-risk population and are asymptomatic, there is not enough evidence to prove that there is any benefit in screening for vitamin D deficiency.

Pregnancy also poses as another high risk factor for vitamin D deficiency. The status levels of vitamin D during the last stages of pregnancy directly impact the new borns first initial months of life. Babies who are exclusively breastfed with minimal exposure to sunlight or supplementation can be at greater risk of vitamin D deficiency,as human milk has minimal vitamin D present. Recommendations for infants of the age 0–12 months are set at 5 ug/day, to assist in preventing rickets in young babies. 80% of dark skinned and or veiled women in Melbourne were found to have serum levels lower than 22.5 nmol/L considering them to be within moderate ranges of vitamin D deficiency.

Australia's vitamin D deficiency levels in recent years have been on the increase, due to factors such as the long-term success of SunSmart government campaigns like Slip, Slop, Slap as well as Cancer Council Australia that have increased the general public's awareness of the risks associated with excessive sun exposure and skin cancers. The 'sun smart' campaign created in 1988 had a significant impact on the public approach and behaviours towards sun exposure. The success of this campaign reduced the sunburn rate by 50%, which researchers believe to have contributed to the rise in vitamin D deficiencies across Australia.

In addition to the reduced sun exposure amongst the Australia populations, there have been decreases in the form of dietary intake as many people are no longer taking fatty fish oil tablets as a method of regulating vitamin D.

Other factors previously mentioned are sun exposure, geographical longitude as well as season change. Greater latitudes receive sunlight that is of lesser ultra radiation strength in contrast to regions close to the equator, who receive lower variation to hours of daylight during the summer periods.

Excessive exposure to sunlight poses no risk in vitamin D toxicity through overproduction of vitamin D precursor, cholecalciferol, regulating vitamin D production. During ultraviolet exposure, the concentration of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded. This process is less efficient with increased melanin pigmentation in the skin. Endogenous production with full body exposure to sunlight is comparable to taking an oral dose between 250 µg and 625 µg (10,000 IU and 25,000 IU) per day.

Vitamin D oral supplementation and skin synthesis have a different effect on the transport form of vitamin D, plasma calcifediol concentrations. Endogenously synthesized vitamin D travels mainly with vitamin D-binding protein (DBP), which slows hepatic delivery of vitamin D and the availability in the plasma. In contrast, orally administered vitamin D produces rapid hepatic delivery of vitamin D and increases plasma calcifediol.

It has been questioned whether to ascribe a state of sub-optimal vitamin D status when the annual variation in ultraviolet will naturally produce a period of falling levels, and such a seasonal decline has been a part of Europeans' adaptive environment for 1000 generations. Still more contentious is recommending supplementation when those supposedly in need of it are labeled healthy and serious doubts exist as to the long-term effect of attaining and maintaining serum 25(OH)D of at least 80nmol/L by supplementation.

Current theories of the mechanism behind vitamin D toxicity propose that:

- Intake of vitamin D raises calcitriol concentrations in the plasma and cell

- Intake of vitamin D raises plasma calcifediol concentrations which exceed the binding capacity of the DBP, and free calcifediol enters the cell

- Intake of vitamin D raises the concentration of vitamin D metabolites which exceed DBP binding capacity and free calcitriol enters the cell

All of which affect gene transcription and overwhelm the vitamin D signal transduction process, leading to vitamin D toxicity.

Based on risk assessment, a safe upper intake level of 250 µg (10,000 IU) per day in healthy adult has been suggested by non-government authors. However, no government has a UL higher than 4,000 IU.

In the United States, overdose exposure to all formulations of "vitamins" was reported by 62,562 individuals in 2004 (nearly 80% [~78%, n=48,989] of these exposures were in children under the age of 6), leading to 53 "major" life-threatening outcomes and 3 deaths (2 from vitamins D and E; 1 from polyvitaminic type formula, with iron and no fluoride). This may be compared to the 19,250 people who died of unintentional poisoning of all kinds in the U.S. in the same year (2004). In 2010, 71,000 exposures to various vitamins and multivitamin-mineral formulations were reported to poison control centers, which resulted in 15 major reactions but no deaths.

Before 1998, several deaths per year were associated with pharmaceutical iron-containing supplements, especially brightly colored, sugar-coated, high-potency iron supplements, and most deaths were children. Unit packaging restrictions on supplements with more than 30 mg of iron have since reduced deaths to 0 or 1 per year. These statistics compare with 59 confirmed deaths due to aspirin poisoning in 2003 and 147 deaths known to be associated with acetaminophen-containing products in 2003.

The prevalence of vitamin K deficiency varies by geographic region. For infants in the United States, vitamin K deficiency without bleeding may occur in as many as 50% of infants younger than 5 days old, with the classic hemorrhagic disease occurring in 0.25-1.7% of infants. Therefore, the Committee on Nutrition of the American Academy of Pediatrics recommends that 0.5 to 1.0 mg Vitamin K be administered to all newborns shortly after birth.

Postmenopausal and elderly women in Thailand have high risk of Vitamin K deficiency, compared with the normal value of young, reproductive females.

Current dosage recommendations for Vitamin K may be too low. The deposition of calcium in soft tissues, including arterial walls, is quite common, especially in those suffering from atherosclerosis, suggesting that Vitamin K deficiency is more common than previously thought.

Because colonic bacteria synthesize a significant portion of the Vitamin K required for human needs, individuals with disruptions to or insufficient amounts of these bacteria can be at risk for Vitamin K deficiency. Newborns, as mentioned above, fit into this category, as their colons are frequently not adequately colonized in the first five to seven days of life. (Consumption of the mother's milk can undo this temporary problem.) Another at-risk population comprises those individuals on any sort of long-term antibiotic therapy, as this can diminish the population of normal gut flora.

With few exceptions, like some vitamins from B-complex, hypervitaminosis usually occurs more with fat-soluble vitamins (D, E, K and A or 'DEKA'), which are stored in the liver and fatty tissues of the body. These vitamins build up and remain for a longer time in the body than water-soluble vitamins.

Conditions include:

- Hypervitaminosis A

- Hypervitaminosis D

- Hypervitaminosis E

- Hypervitaminosis K, unique as the true upper limit is less clear as is its bioavailability.

According to Williams' Essentials of Diet and Nutrition Therapy it is difficult to set a DRI for vitamin K because part of the requirement can be met by intestinal bacterial synthesis.

- Reliable information is lacking as to the vitamin K content of many foods or its bioavailability. With this in mind the Expert Committee established an AI rather than an RDA.

- This RDA (AI for men age 19 and older is 120 µg/day, AI for women is 90 µg/day) is adequate to preserve blood clotting, but the correct intake needed for optimum bone health is unknown. Toxicity has not been reported.

High-dosage A; high-dosage, slow-release vitamin B; and very high-dosage vitamin B alone (i.e. without vitamin B complex) hypervitaminoses are sometimes associated with side effects that usually rapidly cease with supplement reduction or cessation.

High doses of mineral supplements can also lead to side effects and toxicity. Mineral-supplement poisoning does occur occasionally, most often due to excessive intake of iron-containing supplements.

Menaquinone (vitamin K), but not phylloquinone (vitamin K), intake is associated with reduced risk of CHD mortality, all-cause mortality and severe aortic calcification.

A vitamin deficiency can cause a disease or syndrome known as an avitaminosis or hypovitaminosis. This usually refers to a long-term deficiency of a vitamin. When caused by inadequate nutrition it can be classed as a "primary deficiency", and when due to an underlying disorder such as malabsorption it can be classed as a "secondary deficiency". An underlying disorder may be metabolic as in a defect converting tryptophan to niacin. It can also be the result of lifestyle choices including smoking and alcohol consumption.

Examples are vitamin A deficiency, folate deficiency, scurvy, vitamin D deficiency, vitamin E deficiency, and vitamin K deficiency. In the medical literature, any of these may also be called by names on the pattern of "hypovitaminosis" or "avitaminosis" + "[letter of vitamin]", for example, hypovitaminosis A, hypovitaminosis C, hypovitaminosis D.

Conversely hypervitaminosis is the syndrome of symptoms caused by over-retention of fat-soluble vitamins in the body.

- Vitamin A deficiency can cause keratomalacia.

- Thiamine (vitamin B1) deficiency causes beriberi and Wernicke–Korsakoff syndrome.

- Riboflavin (vitamin B2) deficiency causes ariboflavinosis.

- Niacin (vitamin B3) deficiency causes pellagra.

- Pantothenic acid (vitamin B5) deficiency causes chronic paresthesia.

- Vitamin B6

- Biotin (vitamin B7) deficiency negatively affects fertility and hair/skin growth. Deficiency can be caused by poor diet or genetic factors (such as mutations in the BTD gene, see multiple carboxylase deficiency).

- Folate (vitamin B9) deficiency is associated with numerous health problems. Fortification of certain foods with folate has drastically reduced the incidence of neural tube defects in countries where such fortification takes place. Deficiency can result from poor diet or genetic factors (such as mutations in the MTHFR gene that lead to compromised folate metabolism).

- Vitamin B12 (cobalamin) deficiency can lead to pernicious anemia, megaloblastic anemia, subacute combined degeneration of spinal cord, and methylmalonic acidemia among other conditions.

- Vitamin C (ascorbic acid) short-term deficiency can lead to weakness, weight loss and general aches and pains. Longer-term depletion may affect the connective tissue. Persistent vitamin C deficiency leads to scurvy.

- Vitamin D (cholecalciferol) deficiency is a known cause of rickets, and has been linked to numerous health problems.

- Vitamin E deficiency causes nerve problems due to poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function.

- Vitamin K (phylloquinone or menaquinone) deficiency causes impaired coagulation and has also been implicated in osteoporosis

Treatment involves increasing dietary intake of calcium, phosphates and vitamin D. Exposure to ultraviolet B light (most easily obtained when the sun is highest in the sky), cod liver oil, halibut-liver oil, and viosterol are all sources of vitamin D.

A sufficient amount of ultraviolet B light in sunlight each day and adequate supplies of calcium and phosphorus in the diet can prevent rickets. Darker-skinned people need to be exposed longer to the ultraviolet rays. The replacement of vitamin D has been proven to correct rickets using these methods of ultraviolet light therapy and medicine.

Recommendations are for 400 international units (IU) of vitamin D a day for infants and children. Children who do not get adequate amounts of vitamin D are at increased risk of rickets. Vitamin D is essential for allowing the body to uptake calcium for use in proper bone calcification and maintenance.

Sufficient vitamin D levels can also be achieved through dietary supplementation and/or exposure to sunlight. Vitamin D (cholecalciferol) is the preferred form since it is more readily absorbed than vitamin D. Most dermatologists recommend vitamin D supplementation as an alternative to unprotected ultraviolet exposure due to the increased risk of skin cancer associated with sun exposure. Endogenous production with full body exposure to sunlight is approximately 250 µg (10,000 IU) per day.

According to the American Academy of Pediatrics (AAP), all infants, including those who are exclusively breast-fed, may need vitamin D supplementation until they start drinking at least of vitamin D-fortified milk or formula a day.

Prevention of osteomalacia rests on having an adequate intake of vitamin D and calcium. Vitamin D3 Supplementation is often needed due to the scarcity of Vitamin D sources in the modern diet.

Nutritional osteomalacia responds well to administration of 2,000-10,000 IU of vitamin D3 by mouth daily. Vitamin D3 (cholecalciferol) is typically absorbed more readily than vitmin D2 (ergocalciferol). Osteomalacia due to malabsorption may require treatment by injection or daily oral dosing of significant amounts of vitamin D3.

Zinc has been used therapeutically at a dose of 150 mg/day for months and in some cases for years, and in one case at a dose of up to 2000 mg/day zinc for months. A decrease in copper levels and hematological changes have been reported; however, those changes were completely reversed with the cessation of zinc intake.

However, zinc has been used as zinc gluconate and zinc acetate lozenges for treating the common cold and therefore the safety of usage at about 100 mg/day level is a relevant question. Thus, given that doses of over 150 mg/day for months to years has caused no permanent harm in many cases, a one-week usage of about 100 mg/day of zinc in the form of lozenges would not be expected to cause serious or irreversible adverse health issues in most persons.

Unlike iron, the elimination of zinc is concentration-dependent.

At this time there is no treatment for transaldolase deficiency.

There is currently research being done to find treatments for transaldolase deficiency. A study done in 2009 used orally administered N-acetylcysteine on transaldolase deficient mice and it prevented the symptoms associated with the disease. N-acetylcysteine is a precursor for reduced glutathione, which is decreased in transaldolase deficient patients.

Supplemental zinc can prevent iron absorption, leading to iron deficiency and possible peripheral neuropathy, with loss of sensation in extremities. Zinc and iron should be taken at different times of the day.

Some children with LAL-D have had an experimental therapy called hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplant, to try to prevent the disease from getting worse. Data are sparse but there is a known high risk of serious complications including death, graft-versus-host disease.

Transaldolase deficiency is recognized as a rare inherited pleiotropic metabolic disorder first recognized and described in 2001 that is autosomal recessive. There have been only a few cases that have been noted, as of 2012 there have been 9 patients recognized with this disease and one fetus.

Infants with LAL deficiencies typically show signs of disease in the first weeks of life and if untreated, die within 6–12 months due to multi-organ failure. Older children or adults with LAL-D may remain undiagnosed or be misdiagnosed until they die early from a heart attack or stroke or die suddenly of liver failure. The first enzyme replacement therapy was approved in 2015. In those clinical trials nine infants were followed for one year; 6 of them lived beyond one year. Older children and adults were followed for 36 weeks.

GSE can result in high risk pregnancies and infertility. Some infertile women have GSE and iron deficiency anemia others have zinc deficiency and birth defects may be attributed to folic acid deficiencies.

It has also been found to be a rare cause of amenorrhea.

Boron deficiency is a pathology which may occur in animals due to a lack of boron. A report given by E. Wayne Johnson et al. at the 2005 Alan D. Leman Swine Conference suggests that boron deficiency produces osteochondrosis in swine that is correctable by addition of 50 ppm of boron to the diet. The amount of boron required by animals and humans is not yet well established.

Avitaminosis. Avitaminosis caused by malabsorption in GSE can result in decline of fat soluble vitamins and vitamin B, as well as malabsorption of essential fatty acids. This can cause a wide variety of secondary problems. Hypocalcinemia is also associated with GSE. In treated GSE, the restrictions on diet as well as reduced absorption as a result of prolonged damage may result in post treatment deficiencies.

- Vitamin A – Poor absorption of vitamin A has been seen in coeliac disease. and it has been suggested that GSE-associated cancers of the esophagus may be related to vitamin A deficiency

- Folate deficiency – Folate deficiency is believed to be primary to the following secondary conditions:

- Megaloblastic anemia

- Calcification of brain channels – epilepsy, dementia, visual manifestations.

- B deficiency. Vitamin B deficiency can result in neuropathies and increases in pain sensitivity. may explain some of the peripheral neuropathies, pain and depression associated with GSE.

- B deficiency

- Megaloblastic anemia

- Pernicious anemia

- Vitamin D deficiency. Vitamin D deficiency can result in osteopenia and osteoporosis

- Hypocalcemia

- Vitamin K – Coeliac disease has been identified in patients with a pattern of bleeding that treatment of vitamin K increased levels of prothrombin.

- Vitamin E – deficiency of vitamin E can lead to CNS problems and possibly associated with myopathy

Mineral deficiencies. GSE is associated with the following mineral deficiencies:

- Calcium – Hypocalcemia causing Oesteopenia

- Magnesium – hypomagnesemia, may lead to parathyroid abnormalities.

- Iron – Iron deficiency anemia

- Phosphorus – hypophosphatemia, causing Oesteopenia

- Zinc – Zinc deficiencies are believed to be associated with increased risk of Esophagus Carcinoma

- Copper – deficiency

- Selenium – deficiency – Selenium and Zinc deficiencies may play a role increasing risk of cancer. Selenium deficiency may also be an aggravating factor for autoimmune hyperthyroidism (Graves disease).

Blood factors

- Carnitine – deficiency.

- Prolactin – deficiency (childhood).

- homocysteine – excess.

There is no treatment for MKD. But, the inflammation and the other effects can be reduced to a certain extent.

- IL-1 targeting drugs can be used to reduce the effects of the disorder. Anakinra is antagonist to IL-1 receptors. Anakinra binds the IL-1 receptor, preventing the actions of both IL-1α and IL-1β, and it has been proved to reduce the clinical and biochemical inflammation in MKD. It can effectively decreases the frequency as well as the severity of inflammatory attacks when used on a daily basis. Disadvantages with the usage of this drug are occurrence of painful injection site reaction and as the drug is discontinued in the near future the febrile attacks start. (Examined in a 12-year-old patient).

- Canakinumab is a long acting monoclonal antibody which is directed against IL-1β has shown to be effective in reducing both frequency and severity in patients suffering from mild and severe MKD in case reports and observational case series. It reduces the physiological effects but the biochemical parameter still remain elevated (Galeotti et al. demonstrated that it is more effective than anakinra –considered 6 patients suffering from MKD).

- Anti-TNF therapy might be effective in MKD, but the effect is mostly partial and therapy failure and clinical deterioration have been described frequently in patients on infliximab or etanercept. A beneficial effect of human monoclonal anti-TNFα antibody adalimumab was seen in a small number of MKD patients.

- Most MKD patients are benefited by anti-IL-1 therapy. However, anti-IL-1-resistant disease may also occur. Example. tocilizumab (a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor). This drug is used when the patients are unresponsive towards Anakinra. (Shendi et al. treated a young woman in whom anakinra was ineffective with tocilizumab). It was found that it was effective in reducing the biochemical and clinical inflammation [30].Stoffels et al. observed reduction of frequency and severity of the inflammatory attacks, although after several months of treatment one of these two patients persistently showed mild inflammatory symptoms in the absence of biochemical inflammatory markers.

- A beneficial effect of hematopoietic stem cell transplantation can be used in severe mevalonate kinase deficiency conditions (Improvement of cerebral myelinisation on MRI after allogenic stem cell transplantation was observed in one girl). But, liver transplantation did not influence febrile attacks in this patient.