The concentration of ketone bodies may vary depending on diet, exercise, degree of metabolic adaptation and genetic factors. Ketosis can be induced when a ketogenic diet is followed for more than 3 days. This induced ketosis is sometimes called nutritional ketosis. This table shows the concentrations typically seen under different conditions

Note that urine measurements may not reflect blood concentrations. Urine concentrations are lower with greater hydration, and after adaptation to a ketogenic diet the amount lost in the urine may drop while the metabolism remains ketotic. Most urine strips only measure acetoacetate, while when ketosis is more severe the predominant ketone body is β-hydroxybutyrate. Unlike glucose, ketones are excreted into urine at any blood level. Ketoacidosis is a metabolic derangement that cannot occur in a healthy individual who can produce insulin, and should not be confused with physiologic ketosis.

To treat people with a deficiency of this enzyme, they must avoid needing gluconeogenesis to make glucose. This can be accomplished by not fasting for long periods, and eating high-carbohydrate food. They should avoid fructose containing foods (as well as sucrose which breaks down to fructose).

As with all single-gene metabolic disorders, there is always hope for genetic therapy, inserting a healthy copy of the gene into existing liver cells.

Infants are routinely screened for galactosemia in the United States, and the diagnosis is made while the person is still an infant. Infants affected by galactosemia typically present with symptoms of lethargy, vomiting, diarrhea, failure to thrive, and jaundice. None of these symptoms are specific to galactosemia, often leading to diagnostic delays. Luckily, most infants are diagnosed on newborn screening. If the family of the baby has a history of galactosemia, doctors can test prior to birth by taking a sample of fluid from around the fetus (amniocentesis) or from the placenta (chorionic villus sampling or CVS).

A galactosemia test is a blood test (from the heel of the infant) or urine test that checks for three enzymes that are needed to change galactose sugar that is found in milk and milk products into glucose, a sugar that the human body uses for energy. A person with galactosemia doesn't have one of these enzymes. This causes high levels of galactose in the blood or urine.

Galactosemia is normally first detected through newborn screening, or NBS. Affected children can have serious, irreversible effects or even die within days from birth. It is important that newborns be screened for metabolic disorders without delay. Galactosemia can even be detected through NBS before any ingestion of galactose-containing formula or breast milk.

Detection of the disorder through newborn screening (NBS) does not depend on protein or lactose ingestion, and, therefore, it should be identified on the first specimen unless the infant has been transfused. A specimen should be taken prior to transfusion. The enzyme is prone to damage if analysis of the sample is delayed or exposed to high temperatures. The routine NBS is accurate for detection of galactosemia. Two screening tests are used to screen infants affected with galactosemia—the Beutler's test and the Hill test. The Beutler's test screens for galactosemia by detecting the level of enzyme of the infant. Therefore, the ingestion of formula or breast milk does not affect the outcome of this part of the NBS, and the NBS is accurate for detecting galactosemia prior to any ingestion of galactose.

Duarte galactosemia is a milder form of classical galactosemia and usually has no long term side effects.

A wide variety of companies manufacture ketone screening strips. A strip consists of a thin piece of plastic film slightly larger than a matchstick, with a reagent pad on one end that is either dipped into a urine sample or passed through the stream while the user is voiding. The pad is allowed to react for an exact, specified amount of time (it is recommended to use a stopwatch to time this exactly and disregard any resultant colour change after the specified time); its resulting colour is then compared to a graded shade chart indicating a detection range from negative presence of ketones up to a significant quantity. It is worth noting that in severe diabetic ketoacidosis, the dipstix reaction based on sodium nitroprusside may underestimate the level of ketone bodies in the blood. It is sensitive to acetoacetate only, and the ratio of beta-hydroxybutyrate to acetoacetate is shifted from a normal value of around 1:1 up to around 10:1 under severely ketoacetotic conditions, due to a changing redox milieu in the liver. Measuring acetoacetate alone will thus underestimate the accompanying beta-hydroxybutyrate if the standard conversion factor is applied.

Galactose is converted into glucose by the action of three enzymes, known as the Leloir pathway. There are diseases associated with deficiencies of each of these three enzymes:

Several different problems may lead to the diagnosis, usually by two years of age:

- seizures or other manifestations of severe fasting hypoglycemia

- hepatomegaly with abdominal protuberance

- hyperventilation and apparent respiratory distress due to metabolic acidosis

- episodes of vomiting due to metabolic acidosis, often precipitated by minor illness and accompanied by hypoglycemia

Once the diagnosis is suspected, the multiplicity of clinical and laboratory features usually makes a strong circumstantial case. If hepatomegaly, fasting hypoglycemia, and poor growth are accompanied by lactic acidosis, hyperuricemia, hypertriglyceridemia, and enlarged kidneys by ultrasound, gsd I is the most likely diagnosis. The differential diagnosis list includes glycogenoses types III and VI, fructose 1,6-bisphosphatase deficiency, and a few other conditions (page 5), but none are likely to produce all of the features of GSD I.

The next step is usually a carefully monitored fast. Hypoglycemia often occurs within six hours. A critical blood specimen obtained at the time of hypoglycemia typically reveals a mild metabolic acidosis, high free fatty acids and beta-hydroxybutyrate, very low insulin levels, and high levels of glucagon, cortisol, and growth hormone. Administration of intramuscular or intravenous glucagon (0.25 to 1 mg, depending on age) or epinephrine produces little rise of blood sugar.

The diagnosis is definitively confirmed by liver biopsy with electron microscopy and assay of glucose-6-phosphatase activity in the tissue and/or specific gene testing, available in recent years.

Some clinicians regard eliminating carbohydrates as unhealthy and dangerous. However, it is not necessary to eliminate carbohydrates from the diet completely to achieve ketosis. Other clinicians regard ketosis as a safe biochemical process that occurs during the fat-burning state. Ketosis, which is accompanied by gluconeogenesis (the creation of glucose de novo from pyruvate), is the specific state that concerns some clinicians. However, it is unlikely for a normally functioning person to reach life-threatening levels of ketosis, defined as serum beta-hydroxybutyrate (B-OHB) levels above 15 millimolar (mM) compared to ketogenic diets among non diabetics, which "rarely run serum B-OHB levels above 3 mM." This is avoided with proper basal secretion of pancreatic insulin. People who are unable to secrete basal insulin, such as type 1 diabetics and long-term type II diabetics, are liable to enter an unsafe level of ketosis, eventually resulting in a coma that requires emergency medical treatment. The anti-ketosis conclusions have been challenged by a number of doctors and advocates of low-carbohydrate diets, who dispute assertions that the body has a preference for glucose and that there are dangers associated with ketosis.

Screening for ketonuria is done frequently for acutely ill patients, presurgical patients, and pregnant women. Any diabetic patient who has elevated levels of blood and urine glucose should be tested for urinary ketones. In addition, when diabetic treatment is being switched from insulin to oral hypoglycemic agents, the patient's urine should be monitored for ketonuria. The development of ketonuria within 24 hours after insulin withdrawal usually indicates a poor response to the oral hypoglycemic agents. Diabetic patients should have their urine tested regularly for glucose and ketones, particularly when acute infection or other illness develops.

In conditions associated with acidosis, urinary ketones are tested to assess the severity of acidosis and to monitor treatment response. Urine ketones appear before there is any significant increase in blood ketones; therefore, urine ketone measurement is especially helpful in emergency situations.

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.

Without adequate metabolic treatment, patients with GSD I have died in infancy or childhood of overwhelming hypoglycemia and acidosis. Those who survived were stunted in physical growth and delayed in puberty because of chronically low insulin levels. Mental retardation from recurrent, severe hypoglycemia is considered preventable with appropriate treatment.

Hepatic complications have been serious in some patients. Adenomas of the liver can develop in the second decade or later, with a small chance of later malignant transformation to hepatoma or hepatic carcinomas (detectable by alpha-fetoprotein screening). Several children with advanced hepatic complications have improved after liver transplantation.

Additional problems reported in adolescents and adults with GSD I have included hyperuricemic gout, pancreatitis, and chronic renal failure. Despite hyperlipidemia, atherosclerotic complications are uncommon.

With diagnosis before serious harm occurs, prompt reversal of acidotic episodes, and appropriate long-term treatment, most children will be healthy. With exceptions and qualifications, adult health and life span may also be fairly good, although lack of effective treatment before the mid-1970s means information on long-term efficacy is limited.

Dozens of congenital metabolic diseases are now detectable by newborn screening tests, especially the expanded testing using mass spectrometry. This is an increasingly common way for the diagnosis to be made and sometimes results in earlier treatment and a better outcome. There is a revolutionary Gas chromatography–mass spectrometry-based technology with an integrated analytics system, which has now made it possible to test a newborn for over 100 mm genetic metabolic disorders.

Because of the multiplicity of conditions, many different diagnostic tests are used for screening. An abnormal result is often followed by a subsequent "definitive test" to confirm the suspected diagnosis.

Common screening tests used in the last sixty years:

- Ferric chloride test (turned colors in reaction to various abnormal metabolites in urine)

- Ninhydrin paper chromatography (detected abnormal amino acid patterns)

- Guthrie bacterial inhibition assay (detected a few amino acids in excessive amounts in blood) The dried blood spot can be used for multianalyte testing using Tandem Mass Spectrometry (MS/MS). This given an indication for a disorder. The same has to be further confirmed by enzyme assays, IEX-Ninhydrin, GC/MS or DNA Testing.

- Quantitative measurement of amino acids in plasma and urine

- IEX-Ninhydrin post column derivitization liquid ion-exchange chromatography (detected abnormal amino acid patterns and quantitative analysis)

- Urine organic acid analysis by gas chromatography–mass spectrometry

- Plasma acylcarnitines analysis by mass spectrometry

- Urine purines and pyrimidines analysis by gas chromatography-mass spectrometry

Specific diagnostic tests (or focused screening for a small set of disorders):

- Tissue biopsy or necropsy: liver, muscle, brain, bone marrow

- Skin biopsy and fibroblast cultivation for specific enzyme testing

- Specific DNA testing

A 2015 review reported that even with all these diagnostic tests, there are cases when "biochemical testing, gene sequencing, and enzymatic testing can neither confirm nor rule out an IEM, resulting in the need to rely on the patient's clinical course."

In terms of the diagnosis for glycogen storage disease type III, the following tests/exams are carried out to determine if the individual has the condition:

- Biopsy (muscle or liver)

- CBC

- Ultrasound

- DNA mutation analysis (helps ascertain GSD III subtype)

The differential diagnosis of glycogen storage disease type III includes GSD I, GSD IX and GSD VI. This however does not mean other glycogen storage diseases should not be distinguished as well.

The diagnosis is based on a combination of typical clinical features and exclusion by a pediatric endocrinologist of other causes of "hypoglycemia with ketosis," especially growth hormone deficiency, hypopituitarism, adrenal insufficiency, and identifiable inborn errors of metabolism such as organic acidoses.

The most useful diagnostic tests include measurement of insulin, growth hormone, cortisol, and lactic acid at the time of the hypoglycemia. Plasma acylcarnitine levels and urine organic acids exclude some of the important metabolic diseases. When the episodes are recurrent or severe, the definitive test is a hospitalization for a supervised diagnostic fast. This usually demonstrates "accelerated fasting"—a shorter time until the glucose begins to fall, but normal metabolic and counterregulatory responses as the glucose falls. As the glucose reaches hypoglycemic levels, the insulin is undetectable, counterregulatory hormones, fatty acids, and ketones are high, and glucagon injection elicits no rise of glucose.

The International Diabetes Federation consensus worldwide definition of the metabolic syndrome (2006) is:

Central obesity (defined as waist circumference with ethnicity-specific values) AND any two of the following:

- Raised triglycerides: > 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality

- Reduced HDL cholesterol: < 40 mg/dL (1.03 mmol/L) in males, < 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality

- Raised blood pressure (BP): systolic BP > 130 or diastolic BP >85 mm Hg, or treatment of previously diagnosed hypertension

- Raised fasting plasma glucose (FPG): >100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes

If FPG is >5.6 mmol/L or 100 mg/dL, an oral glucose tolerance test is strongly recommended, but is not necessary to define presence of the syndrome.

Children's blood sugar levels are often slightly lower than adults'. Overnight fasting glucose levels are below 70 mg/dL (3.9 mM) in 5% of healthy adults, but up to 5% of children can be below 60 mg/dL (3.3 mM) in the morning fasting state. As the duration of fasting is extended, a higher percentage of infants and children will have mildly low plasma glucose levels, usually without symptoms. The normal range of newborn blood sugars continues to be debated. It has been proposed that newborn brains are able to use alternate fuels when glucose levels are low more readily than adults. Experts continue to debate the significance and risk of such levels, though the trend has been to recommend maintenance of glucose levels above 60–70 mg/dL the first day after birth.

Diabetic hypoglycemia represents a special case with respect to the relationship of measured glucose and hypoglycemic symptoms for several reasons. First, although home glucose meter readings are often misleading, the probability that a low reading, whether accompanied by symptoms or not, represents real hypoglycemia is much higher in a person who takes insulin than in someone who does not.

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 maple syrup urine disease.

Newborn screening for maple syrup urine disease involves analyzing the blood of 1–2 day-old newborns through tandem mass spectrometry. The blood concentration of leucine and isoleucine is measured relative to other amino acids to determine if the newborn has a high level of branched-chain amino acids. Once the newborn is 2–3 days old the blood concentration of branched-chain amino acids like leucine is greater than 1000 µmol/L and alternative screening methods are used. Instead, the newborn’s urine is analyzed for levels of branched-chain alpha-hydroxyacids and alpha-ketoacids.

The World Health Organization 1999 criteria require the presence of any one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, AND two of the following:

- Blood pressure: ≥ 140/90 mmHg

- Dyslipidemia: triglycerides (TG): ≥ 1.695 mmol/L and high-density lipoprotein cholesterol (HDL-C) ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female)

- Central obesity: waist:hip ratio > 0.90 (male); > 0.85 (female), or body mass index > 30 kg/m

- Microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g

There are no methods for preventing the manifestation of the pathology of MSUD in infants with two defective copies of the BCKD gene. However, genetic counselors may consult with couples to screen for the disease via DNA testing. DNA testing is also available to identify the disease in an unborn child in the womb.

Treatment is depended on the type of glycogen storage disease. E.g. GSD I is typically treated with frequent small meals of carbohydrates and cornstarch to prevent low blood sugar, while other treatments may include allopurinol and human granulocyte colony stimulating factor.

Children "outgrow" ketotic hypoglycemia, presumably because fasting tolerance improves as body mass increases. In most the episodes become milder and more infrequent by 4 to 5 years of age and rarely occur after age 9. Onset of hypoglycemia with ketosis after age 5 or persistence after age 7 should elicit referral and an intensive search for a more specific disease.

The following is a brief list of hormones and metabolites which may be measured in a critical sample. Not all tests are checked on every patient. A "basic version" would include insulin, cortisol, and electrolytes, with C-peptide and drug screen for adults and growth hormone in children. The value of additional specific tests depends on the most likely diagnoses for an individual patient, based on the circumstances described above. Many of these levels change within minutes, especially if glucose is given, and there is no value in measuring them after the hypoglycemia is reversed. Others, especially those lower in the list, remain abnormal even after hypoglycemia is reversed, and can be usefully measured even if a critical specimen is missed.

Part of the value of the critical sample may simply be the proof that the symptoms are indeed due to hypoglycemia. More often, measurement of certain hormones and metabolites at the time of hypoglycemia indicates which organs and body systems are responding appropriately and which are functioning abnormally. For example, when the blood glucose is low, hormones which raise the glucose should be rising and insulin secretion should be completely suppressed.

Without effective gluconeogenesis (GNG), hypoglycaemia will set in after about 12 hours of fasting. This is the time when liver glycogen stores have been exhausted, and the body has to rely on GNG. When given a dose of glucagon (which would normally increase blood glucose) nothing will happen, as stores are depleted and GNG doesn't work. (In fact, the patient would already have high glucagon levels.)

There is no problem with the metabolism of glucose or galactose, but fructose and glycerol cannot be used by the liver to maintain blood glucose levels. If fructose or glycerol are given, there will be a buildup of phosphorylated three-carbon sugars. This leads to phosphate depletion within the cells, and also in the blood. Without phosphate, ATP cannot be made, and many cell processes cannot occur.

High levels of glucagon will tend to release fatty acids from adipose tissue, and this will combine with glycerol that cannot be used in the liver, to make triacylglycerides causing a fatty liver.

As three carbon molecules cannot be used to make glucose, they will instead be made into pyruvate and lactate. These acids cause a drop in the pH of the blood (a metabolic acidosis). Acetyl CoA (acetyl co-enzyme A) will also build up, leading to the creation of ketone bodies.

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

An example is lactose intolerance.

Carbohydrates account for a major portion of the human diet. These carbohydrates are composed of three principal monosaccharides: glucose, fructose and galactose; in addition glycogen is the storage form of carbohydrates in humans. The failure to effectively use these molecules accounts for the majority of the inborn errors of human carbohydrates metabolism.

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.