The appearance of microvillous inclusion disease on light microscopy is similar to celiac sprue; however, it usually lacks the intraepithelial lymphocytic infiltration characteristic of celiac sprue and stains positive for carcinoembryonic antigen (CEA).

The definitive diagnosis is dependent on electron microscopy.

The differential diagnosis of chronic and intractable diarrhea is:

- Intestinal epithelial dysplasia

- Syndromatic diarrhea

- Immunoinflammatory enteropathy

CCD may be detectable on prenatal ultrasound. After birth, signs in affected babies typically are abdominal distension, visible peristalsis, and watery stools persistent from birth that show chloride loss of more than 90 mmol/l.

An important feature in this diarrhea that helps in the diagnosis, is that it is the only type of diarrhea that causes metabolic alkalosis rather than metabolic acidosis.

Available treatments address the symptoms of CCD, not the underlying defect. Early diagnosis and aggressive salt replacement therapy result in normal growth and development, and generally good outcomes. Replacement of NaCl and KCl has been shown to be effective in children.

A potential treatment is butyrate.

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."

Microscopic analysis of the hair shows twisted hairs of unequal size and different shapes (pili torti, aniso- and poikilotrichosis), longitudinal breaks and breaks located at nodes (trichorrhexis nodosa). Scanning electron microscopy might reveal hair budding (trichorrhexis blastysis). Biochemical analysis may reveal sulfur-deficient brittle hair (trichothiodystrophy; note that disulfide bonds determine hair waviness).

Platelets may be enlarged. The membrane surface connected canalicular system is disrupted with prominent tubules and small membranous vesicles. Alpha granules may be missing from the platelets. Despite these abnormalities there is no increased tendency to bleed in this syndrome.

In order to be diagnosed with AGU an individual takes a urine test, which will show indication of an increased amount of aspartylglucosamin being secreted. The confirmation of the diagnosis of aspartylglucosaminuria requires a blood test. This helps show if the enzyme aspartylglucosaminidase is present or partially absent. A skin simple will also show the amount of aspartylglucosaminidase present.

The diagnosis of Nezelof syndrome will indicate a deficiency of T-cells, additionally in ascertaining the condition the following is done:

When families have a child who has already been diagnosed with AGU, they have the option to observe the enzyme's activity that codes for AGU in future pregnancy, to help determine if the next child will also have a positive diagnosis for aspartylglucosaminuria.

The diagnosis is based on the biochemical findings (increased concentrations of lysine, arginine and ornithine in urine and low concentrations of these amino acids in plasma, elevation of urinary orotic acid excretion after protein-rich meals, and inappropriately high concentrations of serum ferritin and lactate dehydrogenase isoenzymes) and the screening of known mutations of the causative gene from a DNA sample.

The differential diagnosis for this condition consists of acquired immune deficiency syndrome and severe combined immunodeficiency syndrome

Treatment of LPI consists of protein-restricted diet and supplementation with oral citrulline. Citrulline is a neutral amino acid that improves the function of the urea cycle and allows sufficient protein intake without hyperammonemia. Under proper dietary control and supplementation, the majority of the LPI patients are able to have a nearly normal life. However, severe complications including pulmonary alveolar proteinosis and renal insufficiency may develop even with proper treatment.

Fertility appears to be normal in women, but mothers with LPI have an increased risk for complications during pregnancy and delivery.

A diagnosis of this disorder can be made by measuring urine to look for elevated levels of free sialic acid. Prenatal testing is also available for known carriers of this disorder.

Diagnosis can be made at birth by identifying the symptoms of the child. Ultrastructural diagnosis where tissues are analyzed is using electron microscopy is also conducted. A specimen of skin is obtained via a skin biopsy and analyzed to see any tell tale characteristics.Genetic testing can also be done to identify the mutation on the FATP4 gene associated with fatty acid synthesis. Genetic consultation through a genetic counsellor is done to determine whether the individual has this syndrome and reduces the chances of misdiagnoses with other cutaneous diseases.

There is no single, specific test for malabsorption. As for most medical conditions, investigation is guided by symptoms and signs. A range of different conditions can produce malabsorption and it is necessary to look for each of these specifically. Many tests have been advocated, and some, such as tests for pancreatic function are complex, vary between centers and have not been widely adopted. However, better tests have become available with greater ease of use, better sensitivity and specificity for the causative conditions. Tests are also needed to detect the systemic effects of deficiency of the malabsorbed nutrients (such as anaemia with vitamin B12 malabsorption).

The prevalence of this disorder has been estimated to be 1/50,000-100,000 per live births in Western Europe. It appears to be higher in areas with high degree of consanguinity and in patients of Arabic origin.

The infants present in the first few days of life with watery diarrhoea. This leads rapidly to dehydration and electrolyte imbalance and metabolic decompensation. Enteral feeding with a protein hydrolysate or amino acid based formulas worsen the diarrhoea and the children rapidly fail to thrive and develop protein energy malnutrition.

In the majority of cases the severity of the malabsorption and diarrhoea make them dependent on daily long term total parentral nutrition.

Hepatic fibrosis and cirrhosis are known complications.

Bowel transplantation may be an option.

In the middle of the 20th century the principal treatment for some of the amino acid disorders was restriction of dietary protein and all other care was simply management of complications. In the past twenty years, enzyme replacement, gene therapy, and organ transplantation have become available and beneficial for many previously untreatable disorders. Some of the more common or promising therapies are listed:

The diagnosis of Mulibrey nanism can be done via genetic testing, as well as by the physical characteristics (signs/symptoms) displayed by the individual.

The diagnosis of an individual with acrodermatitis enteropathica includes each of the following:

- Plasma zinc level (lab)

- Light microscopy (skin biopsy)

- Electron microscopy (histology)

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.

An examination reveals massive fluid retention and generalized swelling. Abnormal sounds are heard when listening to the heart and lungs with a stethoscope. Blood pressure may be high. The patient may have signs of malnutrition.

A urinalysis reveals large amounts of protein and the presence of fat in the urine. Total protein in the blood may be low. The disorder can be screened during pregnancy by finding elevated levels of alpha-fetoprotein on a routine sampling of amniotic fluid. Genetic tests should be used to confirm the diagnosis, if the screening test is positive.

CNF is one of the Finnish heritage diseases. By use of positional cloning strategies, Kestila et al. isolated the gene responsible for NPHS1. Mutations in Finnish patients with NPHS1 were found in this gene, which they termed nephrin. The most common Finnish mutation was a deletion of 2 nucleotides in exon 2 (602716.0001), resulting in a frameshift and a truncated protein. The predicted nephrin protein belongs to the immunoglobulin family of cell adhesion molecules and is specifically expressed in renal glomeruli. It was also observed that, in most cases, alleles typically found on CNF chromosomes of Finnish families were also found on CNF chromosomes of non-Finnish families from North America and Europe.

Frequent infections may occur over the course of the disease.

Bile acid malabsorption is common in Crohn's disease but not always recognised. Most patients with previous ileal resection and chronic diarrhea will have abnormal SeHCAT tests and can benefit from bile acid sequestrants.

Patients with primary bile acid diarrhea are frequently misdiagnosed as having the irritable bowel syndrome as clinicians fail to recognize the condition. When SeHCAT testing is performed, the diagnosis of primary bile acid diarrhea is commonly made. In a review of 18 studies of the use of SeHCAT testing in diarrhea-predominant irritable bowel syndrome patients, 32% of 1223 patients had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a bile acid sequestrant.

Estimates of the population prevalence taken from this review suggest that 1% of the adult population could have primary bile acid diarrhea (Type 2 bile acid malabsorption).

There are no life-threatening complications after the perinatal period (around the time of birth) and the skin conditions persist but to a lesser degree of severity. Individuals have a favourable prognosis as symptoms can be managed and past the infancy stage are not life-threatening. The red skin edema improves after a three-week period but the ichthyosis scaling persists. Asthma has been recorded in some cases later on in the individual's life and sign of atopic dermatitis persist, follicular hyperkeratosis and small amounts of scaling at the scalp that goes on into adulthood but otherwise the individual continues a healthy life.

Besides the clinical picture, fasting VIP plasma level may confirm the diagnosis, and CT scan and somatostatin receptor scintigraphy are used to localise the tumor, which is usually metastatic at presentation.

Tests include:

- Blood chemistry tests (basic or comprehensive metabolic panel)

- CT scan of the abdomen

- MRI of the abdomen

- Stool examination for cause of diarrhea and electrolyte levels

- Vasoactive intestinal peptide (VIP) level in the blood