It is characterized by chronic, intractable diarrhea in new-born infants, starting in the first few days of life.

This results in metabolic acidosis and severe dehydration. Pregnancy and birth are usually normal.

Microvillus inclusion disease, also known as Davidson's disease, congenital microvillus atrophy and, less specifically, microvillus atrophy (note: microvillus is often misspelled as microvillous), is a rare genetic disorder of the small intestine that is inherited in an autosomal recessive pattern.

The main symptoms of AIE include:

- Diarrhea (frequent loss of fluids)

- Intestinal inflammation

- Vomiting

- Intestinal bleeding

- Difficulty or inability to gain weight

- Rapid weight loss

- Decreased urine output from dehydration

Tricho-hepato-enteric syndrome is one particular form of intractable diarrhea of infancy, presenting typically in the first month of life. These babies were usually born small for their age and continue to experience failure to thrive, usually with a final short stature. Typical facial features include prominent forehead and cheeks, a broad nasal root and widely spaced eyes (hypertelorism). Their hairs are woolly, easily removed and poorly pigmented. Liver disease is mainly present as cirrhosis or fibrosis, and staining might reveal high iron content of the liver cells (consistent with hemochromatosis). Most evaluated patients had some degree of decrease in intelligence.

Autoimmune enteropathy (AIE) is a rare disorder of the immune system condition that affects infants, young children and (rarely) adults causing severe diarrhea, vomiting, and other morbidities of the digestive tract. AIE causes malabsorption of food, vitamins, and minerals often necessitating replacement fluids and total parenteral nutrition. Some disorders, such as IPEX Syndrome, include autoimmune enteropathy as well as autoimmune "pathies" of the skin, thyroid, other glands, or kidneys.

CCD causes persistent secretory diarrhea. In a fetus, it leads to polyhydramnios and premature birth. Immediately after birth, it leads to dehydration, hypoelectrolytemia, hyperbilirubinemia, abdominal distention, and failure to thrive.

Tricho-hepato-enteric syndrome (THE), also known as syndromic or phenotypic diarrhea, is an extremely rare congenital bowel disorder which manifests itself as intractable diarrhea in infants with intrauterine growth retardation, hair and facial abnormalities. Many also have liver disease and abnormalities of the immune system. The associated malabsorption leads to malnutrition and failure to thrive.

It is thought to be a genetic disorder with an autosomal recessive inheritance pattern, although responsible genes have not been found and the exact cause remains unknown. Prognosis is poor; many patients die before the age of 5 (mainly from infections or cirrhosis), although most patients nowadays survive with intravenous feeding (parenteral nutrition).

The most common presentation of Milroy Disease is bilateral lower extremity lymphedema, and may also be accompanied by hydrocele.

Infants with LPI are usually symptom-free when breastfed because of the low protein concentration in human milk, but develop vomiting and diarrhea after weaning. The patients show failure to thrive, poor appetite, growth retardation, enlarged liver and spleen, prominent osteoporosis and osteopenia, delayed bone age and spontaneous protein aversion. Forced feeding of protein may lead to convulsions and coma. Mental development is normal if prolonged episode of hyperammonemia can be avoided. Some patients develop severe pulmonary and renal complications. High levels of plasma glutamine and glycine are observed.

Affected infants present within a few months after birth with failure to thrive and severe folate deficiency manifested as macrocytic anemia and developmental delays. There can be (i) pancytopenia, (ii) diarrhea and/or mucositis and/or (iii) immune deficiency due to T-cell dysfunction and hypoimmunoglobulinemia resulting in pneumonia usually due to Pneumocystis jirovecii. Recently, several infants with the immune deficiency syndrome were described. Untreated, or with inadequate treatment, there are progressive systemic and neurological signs with a spectrum of manifestations including seizures that are often intractable. Females with HFM are fertile and, if folate sufficient during pregnancy, have normal offspring. Subjects that carry one mutated PCFT allele are normal. The genomic and clinical features of HFM were recently reviewed.

Hereditary folate malabsorption (HFM - OMIM #229050) is a rare autosomal recessive disorder caused by loss-of-function mutations in the proton-coupled folate transporter (PCFT) gene, resulting in systemic folate deficiency and impaired delivery of folate to the brain.

Polyps are most frequent in the stomach and large intestine, are also found in the small intestine, and are least frequent in the esophagus. A biopsy will reveal them to be hamartomas; the possibility that they progress to cancer is generally considered to be low, although it has been reported multiple times in the past. Chronic diarrhea and protein-losing enteropathy are often observed. Possible collateral features include variable anomalies of ectodermal tissues, such as alopecia, atrophy of the nails, or skin pigmentation

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.

The signs/symptoms of protein losing enteropathy are consistent with diarrhea, fever, and general abdominal discomfort. Swelling of the legs due to peripheral edema can also occur, however if the PLE is related to a systemic disease such as congestive heart failure or constrictive pericarditis, then the symptoms could be of the primary disease development.

Lysinuric protein intolerance (LPI), also called hyperdibasic aminoaciduria type 2,cationic aminoaciduria or familial protein intolerance, is an autosomal recessive metabolic disorder affecting amino acid transport.

About 140 patients have been reported, almost half of them of Finnish origin. Individuals from Japan, Italy, Morocco and North Africa have also been reported.

Protein losing enteropathy refers to any condition of the gastrointestinal tract (e.g. damage to the gut wall) that results in a net loss of protein from the body.

Hypertryptophanemia, also called familial hypertryptophanemia, is a rare autosomal recessive metabolic disorder that results in a massive buildup of the amino acid tryptophan in the blood, with associated symptoms and tryptophanuria ("-uria" denotes "in the urine").

Elevated levels of tryptophan are also seen in Hartnup disease, a disorder of amino acid transport. However, the increase of tryptophan in that disorder is negligible when compared to that of hypertryptophanemia.

Milroy's disease (MD) is a familial disease characterized by lymphedema, commonly in the legs, caused by congenital abnormalities in the lymphatic system. Disruption of the normal drainage of lymph leads to fluid accumulation and hypertrophy of soft tissues. It is also known as Milroy disease, Nonne-Milroy-Meige syndrome and hereditary lymphedema.

It was named by Sir William Osler for William Milroy, a Canadian physician, who described a case in 1892, though it was first described by Rudolf Virchow in 1863.

The characteristic symptom of Degos disease is the development of papules. Initially, individuals may have skin lesions or rashes, but they will proceed to develop distinct bumps, or papules. Papules are circular in shape, have a porcelain-white center and red border. As papules age, the white centers will skin in and only the border will remain raised. Typically, papules range from 0.5 to 1 cm in width. Papules appear on the trunk and upper extremities and are not found on the individual's palms, soles, scalp, or face.

Depending on whether an individual has the benign variant or malignant variant of the disease symptoms will vary. Both the benign and malignant forms have development of the characteristic papules. Individuals with the benign form will have the typical papules persisting anywhere from a few years to throughout their whole lives. In the benign form, no inner organs are affected. If an individual develops the malignant form, it means that not only are the papules present, but inner organs are involved. Most malignant cases involve problems of the gastrointestinal tract leading to small intestine lesions, abdominal pain, diarrhea, and bowel perforation. If the central nervous system is involved, symptoms can include headaches, dizziness, seizures, paralysis of cranial nerves, weakness, stroke, damage to small areas of the brain due to artery blockage (cerebral infarcts, and cerebral hemorrhage). Additional organs commonly impacted include the heart, lungs, and kidneys. Symptoms that may develop from damage to these organs include double vision (diploplia), clouding of lenses of eyes, swelling of the optic disc (papilledema), partial loss of vision, shortness of breath, chest pain, epilepsy,and thickening of pericardium.

Someone with the benign form may suddenly develop symptoms of the malignant form. Symptoms can last anywhere from a few weeks to several years. Onset of symptoms typically begins to manifest between the ages of 20-50. A few cases of this condition in newborns have also been described.

At the beginning, affected individuals often notice the loss of pain and temperature sensation or all sensory modalities in their feet. As the disease progresses, the sensory abnormalities may extend up to the knees. However, they often do not notice sensory loss for a long time. Many affected individuals only become aware of the disease when they notice painless injuries and burns or when they seek medical advice for slowly healing wounds or foot ulcers. Foot ulcerations may appear due to permanent pressure, such as long walks or badly fitting shoes. Minor wounds or blisters may then lead to deep foot ulcerations. Once infection occurs, complications such as inflammation and destruction of the underlying bones may follow. Affected individuals who do not lose sensation may experience spontaneous pain. In addition, many affected individuals exhibit, to a variable degree, symmetrical distal muscle weakness and wasting.

HSAN I is characterized by marked sensory disturbances mainly as the loss of pain and temperature sensation in the distal parts of the lower limbs. The loss of sensation can also extend to the proximal parts of the lower limbs and the upper limbs as the disease progresses. Some affected individuals do not lose sensation, but instead experience severe shooting, burning, and lancinating pains in the limbs or in the trunk. Autonomic disturbances, if present, manifest as decreased sweating. The degree of motor disturbances is highly variable, even within families, ranging from absent to severe distal muscle weakness and wasting.

The disease progresses slowly, but often disables the affected individuals severely after a long duration. The onset of the disease varies between the 2nd and 5th decade of life, albeit congenital or childhood onset has occasionally been reported. With the progression of the disease, the affected individuals lose the ability to feel pain in their feet and legs. Minor injuries in the painless area can result in slow-healing wounds which, if not immediately recognized, can develop into chronic ulcerations. Once infection occurs, these ulcerations can result in severe complications that lead to foot deformity, such as inflammation of the underlying bones, spontaneous bone fractures, and progressive degeneration of weight-bearing joints. Furthermore, foot deformity promotes skin changes such as hyperkeratosis at pressure points. These complications may necessitate amputation of the affected foot.

Biopsies of severely affected sural nerve (short saphenous nerve) in patients with HSAN I showed evidence of neuronal degeneration. Only a very few myelinated fibers were observed some of which showed a sign of primary (segmental) demyelination. A reasonable number of unmyelinated axons remained, although the presence of stacks of flattened Schwann cell processes suggested unmyelinated axon loss. Electrophysiological testing provides additional evidence that neuronal degeneration underlies the disease. Sensory potentials are usually absent in the lower limbs but are often recordable or even normal in the upper limbs of the patients. In addition, motor conduction is slow, possibly implying a demyelinating process.

Cronkhite–Canada syndrome is a rare syndrome characterized by multiple polyps of the digestive tract. It is sporadic (i.e. it does not seem to be a hereditary disease), and it is currently considered acquired and idiopathic (i.e. cause remains unknown).

About two-thirds of patients are of Japanese descent and the male to female ratio is 2:1. It was characterized in 1955.

AA-amyloidosis with kidney failure is a complication and may develop without overt crises. AA amyloid protein is produced in very large quantities during attacks, and at a low rate between them, and accumulates mainly in the kidney, as well as the heart, spleen, gastrointestinal tract, and thyroid.

There appears to be an increase in the risk for developing particular vasculitis-related diseases (e.g. Henoch–Schönlein purpura), spondylarthropathy, prolonged arthritis of certain joints and protracted myalgia.

There are seven types of attacks. Ninety percent of all patients have their first attack before they are 18 years old. All develop over 2–4 hours and last anywhere from 6 hours to 4 days. Most attacks involve fever.

1. Abdominal attacks, featuring abdominal pain, affect the whole abdomen with all signs of peritonitis (inflammation of abdominal lining), and acute abdominal pain like appendicitis. They occur in 95% of all patients and may lead to unnecessary laparotomy. Incomplete attacks, with local tenderness and normal blood tests, have been reported.

2. Joint attacks mainly occur in large joints, especially in the legs. Usually, only one joint is affected. 75% of all FMF patients experience joint attacks.

3. Chest attacks include pleuritis (inflammation of the pleura) and pericarditis (inflammation of the pericardium). Pleuritis occurs in 40% of patients and makes it difficult to breathe or lie flat, but pericarditis is rare.

4. Scrotal attacks due to inflammation of the tunica vaginalis occurs in up to 5% and may be mistaken for acute scrotum (i.e. testicular torsion).

5. Myalgia (rare in isolation)

6. Erysipeloid (a skin reaction on the legs, rare in isolation)

7. Fever without any of the other symptoms listed above (25%)

A number of abnormalities and symptoms have been observed with hypertryptophanemia.

Musculoskeletal effects include: joint contractures of the elbows and interphalangeal joints of the fingers and thumbs (specifically the distal phalanges), pes planus (fallen arches), an ulnar drift affecting the fingers of both hands (an unusual, yet correctible feature where the fingers slant toward the ulnar side of the forearm), joint pain and laxity, and adduction of the thumbs (where the thumb appears drawn into the palm, related to contracture of the adductor pollicis).

Behavioral, developmental and other anomalies often include: hypersexuality, perceptual hypersensitivity, emotional lability (mood swings), hyperaggressive behavior; hypertelorism (widely-set eyes),

optical strabismus (misalignment) and myopia.

Metabolically, hypertryptophanemia results in tryptophanuria and exhibits significantly elevated serum levels of tryptophan, exceeding 650% of maximum (normal range: 25-73 micromole/l) in some instances.

A product of the bacterial biosynthesis of tryptophan is indole. The excess of tryptophan in hypertryptophanemia also results in substantial excretion of indoleic acids. These findings suggest a possible congenital defect in the metabolic pathway where tryptophan is converted to kynurenine.

HIDS is one of a number of periodic fever syndromes. It is characterised by attacks of fever, arthralgia, skin lesions including cyclical mouth ulcers, and diarrhea. Laboratory features include an acute phase response (elevated CRP and ESR) and markedly elevated IgD (and often IgA), although cases with normal IgD have been described.

It has mainly been described in the Netherlands and France, although the international registry includes a number of cases from other countries.

The differential diagnosis includes fever of unknown origin, familial Mediterranean fever (FMF) and familial Hibernian fever (or TNFα reception associated periodic syndrome/TRAPS).