The term homocystinuria describes an increased excretion of the thiol amino acid homocysteine in urine (and incidentally, also an increased concentration in plasma). The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency. Others include the re-methylation defects (cobalamin defects, methionine sythase deficiency, MTHFR) and vitamin deficiencies (cobalamin (vitamin B12) deficiency, folate (vitamin B9) deficiency, riboflavin deficiency (vitamin B2), pyridoxal phosphate deficiency (vitamin B6)). In light of this information, a combined approach to laboratory diagnosis is required to reach a differential diagnosis.

CBS deficiency may be diagnosed by routine metabolic biochemistry. In the first instance, plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocysteine. Many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g., MTHFR, methionine synthase deficiency and the cobalamin defects) in lieu of the elevated methionine concentration. Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.

The laboratory analysis of homocysteine itself is complicated because most homocysteine (possibly above 85%) is bound to other thiol amino acids and proteins in the form of disulphides (e.g., cysteine in cystine-homocysteine, homocysteine in homocysteine-homocysteine) via disulfide bonds. Since as an equilibrium process the proportion of free homocystene is variable a true value of total homocysteine (free + bound) is useful for confirming diagnosis and particularly for monitoring of treatment efficacy. To this end it is prudent to perform total homocyst(e)ine analysis in which all disulphide bonds are subject to reduction prior to analysis, traditionally by HPLC after derivatisation with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample.

On 9 May 2014, the UK National Screening Committee (UK NSC) announced its recommendation to screen every newborn baby in the UK for four further genetic disorders as part of its NHS Newborn Blood Spot Screening programme, including isovaleric acidemia.

Diagnosis of Fatty-acid metabolism disorder requires extensive lab testing.

Normally, in cases of hypoglycaemia, triglycerides and fatty acids are metabolised to provide glucose/energy. However, in this process, ketones are also produced and ketotic hypoglycaemia is expected. However, in cases where fatty acid metabolism is impaired, a non-ketotic hypoglycaemia may be the result, due to a break in the metabolic pathways for fatty-acid metabolism.

The urine of newborns can be screened for isovaleric acidemia using mass spectrometry, allowing for early diagnosis. Elevations of isovalerylglycine in urine and of isovalerylcarnitine in plasma are found.

1) Detection of orotic acid in urine

2) Deficiency of Enzymes orotate phosphoribosyl transferase and OMP decarboxylase

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

There is no consensus on how to treat LID but one of the options is to treat it as an iron-deficiency anemia with ferrous sulfate (Iron(II) sulfate) at a dose of 100 mg x day in two doses (one at breakfast and the other at dinner) or 3 mg x Kg x day in children (also in two doses) during two or three months. The ideal would be to increase the deposits of body iron, measured as levels of ferritin in serum, trying to achieve a ferritin value between 30 and 100 ng/mL. Another clinical study has shown an increase of ferritin levels in those taking iron compared with others receiving a placebo from persons with LID. With ferritin levels higher than 100 ng/mL an increase in infections, etc. has been reported. Another way to treat LID is with an iron rich diet and in addition ascorbic acid or Vitamin C, contained in many types of fruits as oranges, kiwifruits, etc. that will increase 2 to 5-fold iron absorption.

No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B (also known as pyridoxine). Slightly less than 50% respond to this treatment and need to take supplemental vitamin B for the rest of their lives. Those who do not respond require a Low-sulfur diet (especially monitoring methionine), and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress).

Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i.e., increasing flux through the re-methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys).The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached.

A 2006 study of 279 patients found that of those with symptoms (185, 66%), 95% had suffered an encephalopathic crises usually with following brain damage. Of the persons in the study, 49 children died and the median age of death was 6.6 years. A Kaplan-Meier analysis of the data estimated that about 50% of symptomatic cases would die by the age of 25.

Carnitor - an L-carnitine supplement that has shown to improve the body's metabolism in individuals with low L-carnitine levels. It is only useful for Specific fatty-acid metabolism disease.

Administration of cytidine monophosphate and uridine monophosphate reduces urinary orotic acid and ameliorates the anemia.

Administration of uridine, which is converted to UMP, will bypass the metabolic block and provide the body with a source of pyrimidine.

Uridine triacetate is a drug approved by FDA to be used in the treatment of hereditary orotic aciduria.

Vegetarian diets and, for younger children, breastfeeding are common ways to limit protein intake without endangering tryptophan transport to the brain.

There is a specific pattern of N-acetyl amino acid excretion in the urine. The diagnosis can be confirmed by sequencing of the aminoacylase 1 gene.

Iron deficiency can be avoided by choosing appropriate soil for the growing conditions (e.g., avoid growing acid loving plants on lime soils), or by adding well-rotted manure or compost. If iron deficit chlorosis is suspected then check the pH of the soil with an appropriate test kit or instrument. Take a soil sample at surface and at depth. If the pH is over seven then consider soil remediation that will lower the pH toward the 6.5 - 7 range. Remediation includes: i) adding compost, manure, peat or similar organic matter (warning. Some retail blends of manure and compost have pH in the range 7 - 8 because of added lime. Read the MSDS if available. Beware of herbicide residues in manure. Source manure from a certified organic source.) ii) applying Ammonium Sulphate as a Nitrogen fertilizer (acidifying fertilizer due to decomposition of ammonium ion to nitrate in the soil and root zone) iii) applying elemental Sulphur to the soil (oxidizes over the course of months to produce sulphate/sulphite and lower pH). Note: adding acid directly e.g. sulphuric/hydrochloric/citric acid is dangerous as you may mobilize metal ions in the soil that are toxic and otherwise bound. Iron can be made available immediately to the plant by the use of iron sulphate or iron chelate compounds. Two common iron chelates are Fe EDTA and Fe EDDHA. Iron sulphate (Iron(II)_sulfate) and iron EDTA are only useful in soil up to PH 7.1 but they can be used as a foliar spray (Foliar_feeding). Iron EDDHA is useful up to PH 9 (highly alkaline) but must be applied to the soil and in the evening to avoid photodegradation. EDTA in the soil may mobilize Lead, EDDHA does not appear to.

LID is present in stage 1 and 2, before anemia occurs in stage 3. These first two stages can be interpreted as depletion of iron stores and reduction of effective iron transport.

Stage 1 is characterized by loss of bone marrow iron stores while hemoglobin and serum iron levels remain normal. Serum ferritin falls to less than 20 ng/mL. Increased iron absorption, a compensatory change, results in an increased amount transferrin and consequent increased iron-binding capacity.

Stage 2 - Erythropoiesis is impaired. In spite of an increased level of transferrin, serum iron level is decreased along with transferrin saturation. Erythropoiesis impairment begins when the serum iron level falls to less than 50 μg/dL and transferrin saturation is less than 16%.

In stage 3, anemia (reduced hemoglobin levels) is present but red blood cell appearance remains normal.

Changes in the appearance of red blood cells are the hallmark of stage 4; first microcytosis and then hypochromia develop.

Iron deficiency begins to affect tissues in stage 5, manifesting as symptoms and signs.

A diagnosis can be made by measuring cultured tissue samples for increased levels of free sialic acid. Prenatal testing is also available for known carriers of this disorder.

The gold standard for the diagnosis of Vitamin B deficiency is a low blood level of Vitamin B. A low level of blood Vitamin B is a finding that normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not a diagnosis. Hypovitaminosis B can result from a number of mechanisms, including those listed above. For determination of cause, further patient history, testing, and empirical therapy may be clinically indicated.

A measurement of methylmalonic acid (methylmalonate) can provide an indirect method for partially differentiating Vitamin B and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. Direct measurement of blood cobalamin remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B is one necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. Vitamin B deficiency is but one among the conditions that can lead to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid, the elevated level of which can be detected in the urine and blood.

Due to the lack of available radioactive Vitamin B, the Schilling test is now largely a historical artifact. The Schilling test was performed in the past to help determine the nature of the vitamin B deficiency. An advantage of the Schilling test was that it often included Vitamin B with intrinsic factor.

Diagnosis typically is based on physical signs, X-rays, and improvement after treatment.

It is important for MADD patients to maintain strength and fitness without exercising or working to exhaustion. Learning this balance may be more difficult than normally, as muscle pain and fatigue may be perceived differently from normal individuals.

Symptomatic relief from the effects of MADD may sometimes be achieved by administering ribose orally at a dose of approximately 10 grams per 100 pounds (0.2 g/kg) of body weight per day, and exercise modulation as appropriate. Taken hourly, ribose provides a direct but limited source of energy for the cells. Patients with myoadenylate deaminase deficiency do not retain ribose during heavy exercise, so supplementation may be required to rebuild levels of ATP.

Creatine monohydrate could also be helpful for AMPD patients, as it provides an alternative source of energy for anaerobic muscle tissue and was found to be helpful in the treatment of other, unrelated muscular myopathies.

Aminoacylase 1 deficiency is a rare inborn error of metabolism. To date only 21 cases have been described.

Symptoms include leaves turning yellow or brown in the margins between the veins which may remain green, while young leaves may appear to be bleached. Fruit would be of poor quality and quantity. Any plant may be affected, but raspberries and pears are particularly susceptible, as well as most acid-loving plants such as azaleas and camellias.

The blood film can point towards vitamin deficiency:

- Decreased red blood cell (RBC) count and hemoglobin levels

- Increased mean corpuscular volume (MCV, >100 fL) and mean corpuscular hemoglobin (MCH)

- Normal mean corpuscular hemoglobin concentration (MCHC, 32–36 g/dL)

- The reticulocyte count is decreased due to destruction of fragile and abnormal megaloblastic erythroid precursor.

- The platelet count may be reduced.

- Neutrophil granulocytes may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age.

- Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs).

- Macrocytes (larger than normal RBCs) are present.

- Ovalocytes (oval-shaped RBCs) are present.

- Howell-Jolly bodies (chromosomal remnant) also present.

Blood chemistries will also show:

- An increased lactic acid dehydrogenase (LDH) level. The isozyme is LDH-2 which is typical of the serum and hematopoetic cells.

- Increased homocysteine and methylmalonic acid in Vitamin B deficiency

- Increased homocysteine in folate deficiency

Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.

Bone marrow (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia.

There is no treatment for ISSD. Treatment is limited to controlling the symptoms of this disorder such as administering anti-convulsant medication to control seizure episodes.

The amino acid histidine, when catalyzed by the enzyme histidase, forms urocanic acid. Disruptions in this pathway, caused by a deficiency of histidase, is the underlying cause of histidinemia. This results in reduced levels of skin and serum urocanic acid, the primary indicator of insufficient histidase activity.

In urocanic aciduria, increased urocanic acid in the urine indicates a deficiency of the enzyme urocanase.

With normal to only slightly elevated levels of histidine present in the liver during urocanic aciduria, the only true metabolic indicator of the disorder can be found in the urine.

Urocanic aciduria is thought to be relatively benign. Although aggressive behavior and mental retardation have been reported with the disorder, no definitive neurometabolic connection has yet been established.