The majority of patients is initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutations are known and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.

Because LAL deficiency is inherited, each sibling of an affected individual has a 25% chance of having pathological mutations in LAL genes from both their mother and their father, a 50% chance of having a pathological mutation in only one gene, and a 25% chance of having no pathological mutations. Genetic testing for family members and genetic prenatal diagnosis of pregnancies for women who are at increased risk are possible if family members carrying pathological mutations have been identified.

If the diagnosis of alkaptonuria is suspected, this can be confirmed or excluded by collecting urine for twenty-four hours and determining the amount of homogentisic acid by means of chromatography. There is no validated assay of HGA in blood.

The severity of the symptoms and response to treatment can be quantified through a validated questionnaire titled the AKU Severity Score Index. This includes assigns scores to the presence of particular symptoms and features, such as the presence of eye and skin pigmentation, joint pain, heart problems and organ stones.

D-Glyceric Acidemia should not be confused with L-Glyceric Acidemia (a.k.a. L-glyceric aciduria, a.k.a. primary hyperoxaluria type II ), which is associated with mutations in the "GRHPR" (encoding for the enzyme 'glyoxylate reductase/hydroxypyruvate reductase').

Infants may present with feeding difficulties with frequent vomiting, diarrhea, swelling of the abdomen, and failure to gain weight or sometimes weight loss.

As the disease progresses in infants, increasing fat accumulation in the liver leads to other complications including yellowing of the skin and whites of the eyes (jaundice), and a persistent low-grade fever. An ultrasound examination shows accumulation of chalky material (calcification) in the adrenal gland in about half of infants with LAL-D. Complications of LAL-D progress over time, eventually leading to life-threatening problems such as extremely low levels of circulating red blood cells (severe anemia), liver dysfunction or failure, and physical wasting (cachexia).

People who are older children or adults generally present with a wide range of signs and symptoms that overlap with other disorders. They may have diarrhoea, stomach pain, vomiting, or poor growth, a sign of malabsorption. They may have signs of bile duct problems, like itchiness, jaundice, pale stool, or dark urine. Their feces may be excessively greasy. They often have an enlarged liver, liver disease, and may have yellowish deposits of fat underneath the skin, usually around their eyelids. The disease is often undiagnosed in adults.The person may have a history of premature cardiac disease or premature stroke.

Blood tests may show anaemia and their lipid profiles are generally similar to people with more common familial hypercholesterolemia, including elevated total cholesterol, elevated low-density lipoprotein cholesterol, decreased high-density lipoprotein cholesterol, and elevated serum transaminases.

Liver biopsy findings will generally show a bright yellow-orange color, enlarged, lipid-laden hepatocytes and Kupffer cells, microvesicular and macrovesicular steatosis, fibrosis, and cirrhosis.The only definitive tests are genetic, which may be conducted in any number of ways.

The symptoms of LSD vary, depending on the particular disorder and other variables such as the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness. Some people with LSDhave enlarged livers (hepatomegaly) and enlarged spleens (splenomegaly), pulmonary and cardiac problems, and bones that grow abnormally.

Alkaptonuria does not appear to affect life expectancy, although the last study on the topic is from 1985. The main impact is on quality of life; many people with alkaptonuria have disabling symptoms such as pain, poor sleep and breathing symptoms. These generally start in the fourth decade. The average age at requiring joint replacement surgery is 50–55 years.

Biochemical studies reveal hypophosphatemia (low blood phosphate), elevated alkaline phosphatase and low serum 1, 25 dihydroxyvitamin D levels. Routine laboratory tests do not include serum phosphate levels and this can result in considerable delay in diagnosis. Even when low phosphate is measured, its significance is often overlooked. The next most appropriate test is measurement of urine phosphate levels. If there is inappropriately high urine phosphate (phosphaturia) in the setting of low serum phosphate (hypophosphatemia), there should be a high suspicion for tumor-induced osteomalacia. FGF23 (see below) can be measured to confirm the diagnosis but this test is not widely available.

Once hypophosphatemia and phosphaturia have been identified, a search for the causative tumor should begin. These are small and difficult to define. Gallium-68 DOTA-Octreotate (DOTA-TATE) positron emission tomography (PET) scanning is the best way to locate these tumors. If this scan is not available, other options include Indium-111 Octreotide (Octreoscan) SPECT/CT, whole body CT or MRI imaging.

Serum chemistries are identical in tumor-induced osteomalacia, X-linked hypophosphatemic rickets (XHR) and autosomal dominant hypophosphatemic rickets (ADHR). A negative family history can be useful in distinguishing tumor induced osteomalacia from XHR and ADHR. If necessary, genetic testing for PHEX (phosphate regulating gene with homologies to endopepetidase on the X-chromosome) can be used to conclusively diagnose XHR and testing for the FGF-23 gene will identify patients with ADHR.

D-Bifunctional protein deficiency (officially called 17β-hydroxysteroid dehydrogenase IV deficiency) is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs, such as alcohol. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome.

Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment. Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life.

Glycerate kinase is an enzyme that catalyzes the conversion of D-glyceric acid (a.k.a. D-glycerate) to 2-phosphoglycerate. This conversion is an intermediary reaction found in several metabolic pathways, including the degradation (break-down; catabolism) of serine, as well as the breakdown of fructose.

A deficiency in glycerate kinase activity leads to the accumulation of D-glyceric acid (a.k.a. D-glycerate) in bodily fluids and tissues. D-glyceric acid can be measured in a laboratory that performs "analyte testing" for "organic acids" in blood (plasma) and urine.

Symptoms of the disease (in its most severe form) include progressive neurological impairment, mental/motor retardation, hypotonia, seizures, failure to thrive and metabolic acidosis.

The most common clinical observations of patients suffering from D-bifunctional protein deficiency include hypotonia, facial and skull dysmorphism, neonatal seizures, and neuronal demyelination. High levels of branched fatty acids, such as pristinic acid, bile acid intermediates, and other D-BP substrates are seen to exist. Reduced pristinic acid β-oxidation is a common indicator of D-BP deficiency. D-BP can be distinguished from Zellweger Syndrome by normal plasmalogen synthesis. Recent studies in D-BP knockout mice show compensatory upregulation of other peroxisomal enzymes in absence of D-BP such as palmitoyl-CoA oxidase, peroxisomal thiolase, and branched chain acyl-CoA oxidase.

Hypophosphatemia is diagnosed by measuring the concentration of phosphate in the blood. Concentrations of phosphate less than 0.81 mmol/L (2.5 mg/dL) are considered diagnostic of hypophosphatemia, though additional tests may be needed to identify the underlying cause of the disorder.

Recent studies have explored the connection between DβH deficiency, Droxidopa treatment, and the effect on orthostatic tolerance and glucose homeostasis. It was found that Droxidopa increased acute and late glucose-stimulated insulin secretion and improved patients' insulin sensitivity. However, the use of Droxidopa was found to only produce "modest changes in glucose homeostasis" overall. This shows that treatment modalities other than Droxidopa should be pursued as possible adjuncts for the hyperinsulinemia seen in DβH deficiency.

Standard intravenous preparations of potassium phosphate are available and are routinely used in malnourished patients and alcoholics. Oral supplementation is also useful where no intravenous treatment are available. Historically one of the first demonstrations of this was in concentration camp victims who died soon after being re-fed: it was observed that those given milk (high in phosphate) had a higher survival rate than those who did not get milk.

Monitoring parameters during correction with IV phosphate

- Phosphorus levels should be monitored after 2 to 4 hours after each dose, also monitor serum potassium, calcium and magnesium. Cardiac monitoring is also advised.

As of today, no agreed-upon treatment of Dent's disease is known and no therapy has been formally accepted. Most treatment measures are supportive in nature:

- Thiazide diuretics (i.e. hydrochlorothiazide) have been used with success in reducing the calcium output in urine, but they are also known to cause hypokalemia.

- In rats with diabetes insipidus, thiazide diuretics inhibit the NaCl cotransporter in the renal distal convoluted tubule, leading indirectly to less water and solutes being delivered to the distal tubule. The impairment of Na transport in the distal convoluted tubule induces natriuresis and water loss, while increasing the reabsorption of calcium in this segment in a manner unrelated to sodium transport.

- Amiloride also increases distal tubular calcium reabsorption and has been used as a therapy for idiopathic hypercalciuria.

- A combination of 25 mg of chlorthalidone plus 5 mg of amiloride daily led to a substantial reduction in urine calcium in Dent's patients, but urine pH was "significantly higher in patients with Dent’s disease than in those with idiopathic hypercalciuria (P < 0.03), and supersaturation for uric acid was consequently lower (P < 0.03)."

- For patients with osteomalacia, vitamin D or derivatives have been employed, apparently with success.

- Some lab tests on mice with CLC-5-related tubular damage showed a high-citrate diet preserved kidney function and delayed progress of kidney disease.

Treatment consists of oral bicarbonate supplementation. However, this will increase urinary bicarbonate wasting and may well promote a bicarbonate . The amount of bicarbonate given may have to be very large to stay ahead of the urinary losses. Correction with oral bicarbonate may exacerbate urinary potassium losses and precipitate hypokalemia. As with dRTA, reversal of the chronic acidosis should reverse bone demineralization.

Thiazide diuretics can also be used as treatment by making use of contraction alkalosis caused by them.

This is a form of dysautonomia but differentiated from familial dysautonomia by a lack of familial dysautonomic symptoms such as loss of sense of pain and smell. While L-threo-DOPS has been described as being "very effective for restoring noradrenergic tone and correcting postural hypotension, response to treatment is variable and the long-term and functional outcome is unknown."

Researchers have put together retrospective data collections in order to better under the progression of this orphan disease. Most studies show a perinatal period marked by inadequacy of the ANS to control blood pressure, blood sugar, and body temperature. The experiences of orthostatic hypotension, exercise intolerance, and "traumatic morbidity related to falls and syncope" have been documented later in lives of people with this condition. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation, outcome of these diseases, their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies, a patient registry was established by the non-commercial International Working Group on Neurotransmitter Related Disorders (iNTD).

Familial disorders

- Cystinosis

- Galactosemia

- Glycogen storage disease (type I)

- Hereditary fructose intolerance

- Lowe syndrome

- Tyrosinemia

- Wilson's disease

Acquired disorders

- Amyloidosis

- Multiple myeloma

- Paroxysmal nocturnal hemoglobinuria

- Toxins, such as HAART, ifosfamide, lead, and cadmium

There are 3 possible ways to test the fetal antigen status. Free Cell DNA, Amniocentesis, and Chorionic Villus Sampling. Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans.

- Free Cell DNA can be run on certain antigens. Blood is taken from the mother, and using PCR, can detect the K, C, c, D, and E alleles of fetal DNA. This blood test is non-invasive to the fetus and is an easy way of checking antigen status and risk of HDN. Testing has proven very accurate and is routinely done in the UK at the International Blood Group Reference Laboratory in Bristol. Sanequin laboratory in Amsterdam, Netherlands also performs this test. For US patients, blood may be sent to either of the labs. In the US, Sensigene is done by Sequenome to determine fetal D status. Sequenome does not accept insurance in the US, but US and Canadian patients have had insurance cover the testing done overseas.

- Amniocentesis is another recommended method for testing antigen status and risk for HDN. Fetal antigen status can be tested as early as 15 weeks by PCR of fetal cells.

- CVS is possible as well to test fetal antigen status but is not recommended. CVS carries a higher risk of fetal maternal hemorrhage and can raise antibody titers, potentially worsening the antibody effect.

There are several intervention options available in early, mid and late pregnancies.

There are several intervention options available in early, mid and late pregnancies.

There are 3 possible ways to test the fetal antigen status. Free Cell DNA, Amniocentesis, and Chorionic Villus Sampling. Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans.

- Free Cell DNA can be run on certain antigens. Blood is taken from the mother, and using PCR, can detect the K, C, c, D, and E alleles of fetal DNA. This blood test is non-invasive to the fetus and is an easy way of checking antigen status and risk of HDN. Testing has proven very accurate and is routinely done in the UK at the International Blood Group Reference Laboratory in Bristol. Sanequin laboratory in Amsterdam, Netherlands also performs this test. For US patients, blood may be sent to either of the labs. In the US, Sensigene is done by Sequenome to determine fetal D status. Sequenome does not accept insurance in the US, but US and Canadian patients have had insurance cover the testing done overseas.

- Amniocentesis is another recommended method for testing antigen status and risk for HDN. Fetal antigen status can be tested as early as 15 weeks by PCR of fetal cells.

- CVS is possible as well to test fetal antigen status but is not recommended. CVS carries a higher risk of fetal maternal hemorrhage and can raise antibody titers, potentially worsening the antibody effect.

MCA scans Middle cerebral artery - peak systolic velocity is changing the way sensitized pregnancies are managed. This test is done noninvasively with ultrasound. By measuring the peak velocity of blood flow in the middle cerebral artery, a MoM (multiple of the median) score can be calculated. MoM of 1.5 or greater indicates severe anemia and should be treated with IUT.

There are 3 possible ways to test the fetal antigen status. Free Cell DNA, Amniocentesis, and Chorionic Villus Sampling. Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans.

- Free Cell DNA can be run on certain antigens. Blood is taken from the mother, and using PCR, can detect the K, C, c, D, and E alleles of fetal DNA. This blood test is non-invasive to the fetus and is an easy way of checking antigen status and risk of HDN. Testing has proven very accurate and is routinely done in the UK at the International Blood Group Reference Laboratory in Bristol. Sanequin laboratory in Amsterdam, Netherlands also performs this test. For US patients, blood may be sent to either of the labs. In the US, Sensigene is done by Sequenome to determine fetal D status. Sequenome does not accept insurance in the US, but US and Canadian patients have had insurance cover the testing done overseas.

- Amniocentesis is another recommended method for testing antigen status and risk for HDN. Fetal antigen status can be tested as early as 15 weeks by PCR of fetal cells.

- CVS is possible as well to test fetal antigen status but is not recommended. CVS carries a higher risk of fetal maternal hemorrhage and can raise antibody titers, potentially worsening the antibody effect.

There has been no specific drug therapy developed for hepatitis, with the exception of hepatitis C. Patients are advised to rest in the early stages of the illness, and to eat small, high-calorie, high-protein meals in order to battle anorexia. Larger meals are more easily tolerated in the morning, for patients often experience nausea later in the day. Although high-protein meals are recommended, protein intake should be reduced if signs of precoma — lethargy, confusion, and mental changes — develop.

In acute viral hepatitis, hospitalization is usually required only for patients with severe symptoms (severe nausea, vomiting, change in mental status, and PT greater than 3 seconds above normal) or complications. If the patient experiences continuous vomiting and is unable to maintain oral intake, parenteral nutrition may be required.

In order to relieve nausea and also prevent vomiting, antiemetics (diphenhydramine or prochlorperazine) may be given 30 minutes before meals. However, phenothiazines have a cholestatic effect and should be avoided. The resin cholestyramine may be given only for severe pruritus.