KLS can be diagnosed when there is confusion, apathy, or derealization in addition to frequent bouts of extreme tiredness and prolonged sleep. The earliest it can be diagnosed is the second episode, this is not common. The condition is generally treated as a diagnosis of exclusion. Because KLS is rare, other conditions with similar symptoms are usually considered first.

MRIs can determine if the symptoms are caused by certain brain disorders, stroke, and multiple sclerosis. Lumbar puncture can determine if encephalitis is the cause. KLS must be differentiated from substance abuse by toxicology tests. The use of Electroencephalography (EEG) can exclude temporal status epilepticus from consideration. EEGs are normal in about 70% of KLS patients, but background slowing may sometimes be detected. In addition, low-frequency high-amplitude waves can be observed during waking hours.

Initially, KLS appears similar to bipolar depression. Patients with frontal-lobe syndromes and Klüver-Bucy syndrome also display similar symptoms, but these conditions can be differentiated by the presence of brain lesions. KLS should also be distinguished from very rare cases of menstruation-caused hypersomnia.

Lithium is the only drug that appears to have a preventive effect. In two studies of more than 100 patients, lithium helped prevent recurrence of symptoms in 20% to 40% of cases. The recommended blood level of lithium for KLS patients is 0.8-1.2 mEq/ml. It is not known if other mood stabilizers have an effect on the condition. Anti-depressants do not prevent recurrence.

Children of affected individuals are obligate carriers for aceruloplasminemia. If the CP mutations has been identified in a related individual, prenatal testing is recommended. Siblings of those affected by the disease are at a 25% of aceruloplasminemia. In asymptomatic siblings, serum concentrations of hemoglobin and hemoglobin A1c should be monitored.

To prevent the progression of symptoms of the disease, annual glucose tolerance tests beginning in early teen years to evaluate the onset of diabetes mellitus. Those at risk should avoid taking iron supplements.

As of June 2014 (the latest update on HFM in GeneReviews) a total of 32 families had been reported with a clinical diagnosis of HFM of which there was genotypic confirmation in 24 families. Since then, another two confirmed cases have been reported and an additional case was reported based on a clinical diagnosis alone. Most cases emerge from consanguineous parents with homozygous mutations. There are three instances of HFM from non-consanguineous parents in which there were heterozygous mutations. HFM cases are worldwide with mostly private mutations. However, a number of families of Puerto Rican ancestry have been reported with a common pathogenic variant at a splice receptor site resulting in the deletion of exon 3 and the absence of transport function. A subsequent population-based study of newborn infants in Puerto Rico identified the presence of the same variant on the island. Most of the pathogenic variants result in a complete loss of the PCFT protein or point mutations that result in the complete loss of function. However, residual function can be detected with some of the point mutants.

Diagnosis of this disorder depends on blood tests demonstrating the absence of serum ceruloplasmin, combined with low serum copper concentration, low serum iron concentration, high serum ferritin concentration, or increased hepatic iron concentration. MRI scans can also confirm a diagnosis; abnormal low intensities can indicate iron accumulation in the brain.

Removing the pig from the stressful situation can prevent the episode.

Sedation and glucocorticoids may be beneficial.

Under anaesthesia, dantrolene sodium is a very effective treatment.

Genetic testing enables animals to be removed from the herd if they are positive for the gene. This means that the disorder is rare in the developed world these days.

Stress at slaughter should be minimised in all cases.

HFM must be distinguished from cerebral folate deficiency (CFD)– a condition in which there is normal intestinal folate absorption, without systemic folate deficiency, but a decrease in CSF folate levels. This can accompany a variety of disorders. One form of CFD is due to loss-of-mutations in folate receptor-α, (FRα), which transports folates via an endocytic process. While PCFT is expressed primarily at the basolateral membrane of the choroid plexus, FRα, is expressed primarily at the apical brush-border membrane. Unlike subjects with HFM, patients with CFD present with neurological signs a few years after birth. The basis for the delay in the appearance of clinical manifestations due to loss of FRα function is not clear; the normal blood folate levels may be protective, although for a limited time.

A high-protein diet can overcome the deficient transport of neutral amino acids in most patients. Poor nutrition leads to more frequent and more severe attacks of the disease, which is otherwise asymptomatic. All patients who are symptomatic are advised to use physical and chemical protection from sunlight: avoid excessive exposure to sunlight, wear protective clothing, and use chemical sunscreens with a SPF of 15 or greater. Patients also should avoid other aggravating factors, such as photosensitizing drugs, as much as possible. In patients with niacin deficiency and symptomatic disease, daily supplementation with nicotinic acid or nicotinamide reduces both the number and severity of attacks. Neurologic and psychiatric treatment is needed in patients with severe central nervous system involvement.

People are continually exposed to metals in the environment. Medical tests can detect metals often, but this is to be expected and alone is not evidence that a person is poisoned. Metal screening tests should not be used unless there is reason to believe that a person has had excessive exposure to metals. People should seek medical testing for poisoning only if they are concerned for a particular reason, and physicians should consider a patient's history and physical examination before conducting tests to detect metals.

The diagnosis of harlequin-type ichthyosis relies on both physical examination and certain laboratory tests.

Physical assessment at birth is vital for the initial diagnosis of harlequin ichthyosis. Physical examination reveals characteristic symptoms of the condition especially the abnormalities in the skin surface of newborns. Abnormal findings in physical assessments usually result in employing other diagnostic tests to ascertain the diagnosis.

Genetic testing is the most specific diagnostic test for harlequin ichthyosis. This test reveals a loss of function mutation on the ABCA12 gene. This gene is important in the regulation of protein synthesis for the development of the skin layer. Mutations in the gene may cause impaired transport of lipids in the skin layer and may also lead to shrunken versions of the proteins responsible for skin development. Less severe mutations result in a collodion membrane and congenital ichthyosiform erythroderma-like presentation. ABCA12 is an ATP binding cassette (ABC) transporter, and is a member of a large family of proteins that hydrolyze ATP to transport cargo across membranes. ABCA12 is thought to be a lipid transporter in keratinocytes necessary for lipid transport into lamellar granules during the formation of the lipid barrier.

Biopsy of skin may be done to assess the histologic characteristics of the cells. Histological findings usually reveal hyperkeratotic skin cells, which leads to a thick, white and hard skin layer.

Truckloads or railcar loads of PSS-susceptible pigs may be found with a higher-than-average percentage dead on arrival after stressful events such as transport.

Initial signs of the onset of PSS are pyrexia, panting, sweating, tachycardia and arrhythmias. Chronic cases may show muscle atrophy.

Under halothane anaesthesia, pigs will suddenly become rigid and pyrexic.

The halothane challenge was the historical method of diagnosis.

Genetic testing via a PCR enables affected and carrier animals to be found.

Psychologist Melanie Joy has likened PSS to post-traumatic stress disorder in humans.

While most pregnant women experience some itch from time to time, itching on the palms and soles without a visible rash, or persisting severe or extensive itch symptoms should be reported to the midwife or obstetrican.

To obtain a diagnosis of ICP, there are two LFT (liver function tests) and Serum bile acid test. The liver function tests (LFTs) is a simple blood test, the results of which should be available by the next day. If the ALT level is elevated, this, plus pruritus of palms and soles, could be considered as potentially diagnostic of ICP but only with elevated bile acid levels (however LFTs are not always elevated in ICP patients). The serum bile acid blood test for ICP is a quantitative measurement of bile salts. The results of this test often take longer to return, but the test is more specific for ICP.

Other problems with the liver that occur in pregnancy should be considered by the treating clinician. These include preeclampsia, the HELLP syndrome, and acute fatty liver of pregnancy. Furthermore, other causes of hepatitis, like hepatitis viruses, cancer and certain medications, should also be considered.

Upon diagnosis, many providers will prescribe Ursodeoxycholic Acid. While there is no cure for ICP, and no way to guarantee a successful outcome, studies have shown a slightly better fetal and maternal outcome from administration of Ursodeoxycholic Acid, whereas Cholestyramine appears to only relieve itching.

If additional blood tests to check clotting function identify a problem, giving Vitamin K may help avoid the risk of hemorrhage at delivery.

Delivery by 35–37 completed weeks may be important to fetal outcome as a recent study demonstrated that in severe ICP (defined as bile acids greater than 40 umol/L) the risk of stillbirth was 1.5% compared to 0.5% of uncomplicated pregnancies. This risk rose further if bile acids doubled,

The more common and serious version of Canavan disease typically result in death or development of life-threatening conditions by the age of ten, though life expectancy is variable, and is highly dependent on specific circumstances. On the other hand, the milder variants of the disorder seem not to have any effect on lifespan.

Overexposure to chromium can occur in welders and other workers in the metallurgical industry, persons taking chromium-containing dietary supplements, patients who have received metallic surgical implants, and individuals who ingest chromium salts. Chromium concentrations in whole blood, plasma, serum or urine may be measured to monitor for safety in exposed workers, to confirm the diagnosis in potential poisoning victims, or to assist in the forensic investigation in a case of fatal overdosage.

Copper deficiency is a very rare disease and is often misdiagnosed several times by physicians before concluding the deficiency of copper through differential diagnosis (copper serum test and bone marrow biopsy are usually conclusive in diagnosing copper deficiency). On average, patients are diagnosed with copper deficiency around 1.1 years after their first symptoms are reported to a physician.

Copper deficiency can be treated with either oral copper supplementation or intravenous copper. If zinc intoxication is present, discontinuation of zinc may be sufficient to restore copper levels back to normal, but this usually is a very slow process. People who suffer from zinc intoxication will usually have to take copper supplements in addition to ceasing zinc consumption. Hematological manifestations are often quickly restored back to normal. The progression of the neurological symptoms will be stopped by appropriate treatment, but often with residual neurological disability.

The characteristic hematological (blood) effects of copper deficiency are anemia (which may be microcytic, normocytic or macrocytic) and neutropenia. Thrombocytopenia (low blood platelets) is unusual.

The peripheral blood and bone marrow aspirate findings in copper deficiency can mimic myelodysplastic syndrome. Bone marrow aspirate in both conditions may show dysplasia of blood cell precursors and the presence of ring sideroblasts (erythroblasts containing multiple iron granules around the nucleus). Unlike most cases of myelodysplastic syndrome, the bone marrow aspirate in copper deficiency characteristically shows cytoplasmic vacuoles within red and white cell precursors, and karyotyping in cases of copper deficiency does not reveal cytogenetic features characteristic of myelodysplastic syndrome.

Anemia and neutropenia typically resolve within six weeks of copper replacement.

Cross-tolerance is a phenomenon that occurs when tolerance to the effects of a certain drug produces tolerance to another drug. It often happens between two drugs with similar functions or effects – for example, acting on the same cell receptor or affecting the transmission of certain neurotransmitters. Cross-tolerance has been observed with pharmaceutical drugs such as anti-anxiety agents and illicit substances, and sometimes the two of them together. Often, a person who uses one drug can be tolerant to a drug that has a completely different function. This phenomenon allows one to become tolerant to a drug that they have never even used before.

Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelating agents are molecules that have multiple electron-donating groups, which can form stable coordination complexes with metal ions. Complexation prevents the metal ions from reacting with molecules in the body, and enable them to be dissolved in blood and eliminated in urine. It should only be used in people who have a diagnosis of metal intoxication. That diagnosis should be validated with tests done in appropriate biological samples.

Chelation therapy is administered under very careful medical supervision due to various inherent risks. When the therapy is administered properly, the chelation drugs have significant side effects. Chelation administered inappropriately can cause neurodevelopmental toxicity, increase risk of developing cancer, and cause death; chelation also removes essential metal elements and requires measures to prevent their loss.

Glyceraldehyde 3-phosphate dehydrogenase (abbreviated as GAPDH or less commonly as G3PDH) () is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long established metabolic function, GAPDH has recently been implicated in several non-metabolic processes, including transcription activation, initiation of apoptosis, ER to Golgi vesicle shuttling, and fast axonal, or axoplasmic transport. In sperm, a testis-specific isoenzyme GAPDHS is expressed.

Recent diagnostic criteria have been published out of the Arrhythmia Research Laboratory at the University of Ottawa Heart Institute from Drs. Michael H Gollob and Jason D Roberts.

The Short QT Syndrome diagnostic criterion is based on a point system as follows:

QTc in milliseconds

Jpoint-Tpeak interval

Clinical History

Family History

Genotype

Patients are deemed high-probability (> or equal to 4 points), intermediate probability (3 points) or low probability (2 or less points).

Hartnup disease (also known as "pellagra-like dermatosis" and "Hartnup disorder") is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids (particularly tryptophan that can be, in turn, converted into serotonin, melatonin, and niacin). Niacin is a precursor to nicotinamide, a necessary component of NAD+.

The causative gene, "SLC6A19", is located on chromosome 5.

Routine medical assessments are often prescribed to rule-out or identify a somatic cause for bipolar I symptoms. These tests can include ultrasounds of the head, x-ray computed tomography (CAT scan), electroencephalogram, HIV test, full blood count, thyroid function test, liver function test, urea and creatinine levels and if patient is on lithium, lithium levels are taken. Drug screening includes recreational drugs, particularly synthetic cannabinoids, and exposure to toxins.

In terms of the diagnosis of Romano–Ward syndrome the following is done to ascertain the condition(the "Schwartz Score" helps in so doing):

- Exercise test

- ECG

- Family history

There are drugs that can increase serum HDL such as niacin or gemfibrozil. While these drugs are useful for patients with hyperlipidemia, Tangier's disease patients do not benefit from these pharmaceutical interventions.

Therefore, the only current treatment modality for Tangier's disease is diet modification. A low-fat diet can reduce some of the symptoms, especially those involving neuropathies.