Hematological, biochemical and metabolic investigations on blood and urine between attacks are normal, as are karyotyping and EKG recordings. EKG recordings during attacks show sinus tachycardia. CT, MRI, EMG and nerve conduction studies produce normal results. EEG recordings are normal between attacks but show early-onset tachycardia during attacks. On the Neuropathic Pain Questionnaire patients indicated that pain during attacks is extremely unpleasant and typically felt deep, though also superficial on occasion. Aside from presentation of typical symptoms (see Signs and symptoms above) mutation of the gene "SCN9A" aids in appropriate diagnosis as this gene is mutated in 8 of 14 studied families.

Carbamazepine is at least partly effective at reducing the number or severity of attacks in the majority of PEPD patients. High doses of this drug may be required, perhaps explaining the lack of effect in some individuals. While other anti-epileptic drugs, gabapentin and topiramate, have limited effect in some patients, they have not been shown to be generally effective. Opiate derived analgesics are also largely ineffective, with only sporadic cases of beneficial effect.

Familial dysautonomia is inherited in an autosomal recessive pattern, which means 2 copies of the gene in each cell are altered. If both parents are shown to be carriers by genetic testing, there is a 25% chance that the child will produce FD. Prenatal diagnosis for pregnancies at increased risk for FD by amniocentesis (for 14–17 weeks) or chorionic villus sampling (for 10–11 weeks) is possible.

Genetic testing is performed on a small sample of blood from the tested individual. The DNA is examined with a designed probe specific to the known mutations. The accuracy of the test is above 99%. Dr. Anat Blumenfeld of the Hadasah Medical center in Jerusalem identified chromosome number 9 as the responsible chromosome.

High-voltage pulsed galvanic stimulation (HGVS) has been shown to be of prophylactic benefit, to reduce the incidence of attacks. The patient is usually placed in the left lateral decubitus position and a sterile probe is inserted into the anus. The negative electrode is used and the stimulator is set with a pulse frequency of 80 to 120 cycles per second. The voltage (intensity) is started at 0, progressively raised to a threshold of patient discomfort, and then is decreased to a level that the patient finds comfortable. As the patient's tolerance increases, the voltage can be gradually increased to 250 to 350 Volts. Each treatment session usually lasts between 15 and 60 minutes. Several studies have reported short-term success rates that ranged from 65 to 91%.

Traditional remedies have ranged from warm baths (if the pain lasts long enough to draw a bath), warm to hot enemas, relaxation techniques, and various medications.

Yoga pose "downward facing dog" -Adho Mukha Svanasana, or modification from it seems to help to relax the muscles and ease the pain. The idea of the yoga pose is that the position will force the muscles to relax and therefore tension will relieve over time. Also relaxing one's jaw muscles will help to relax the muscles in rectal area, method used by women giving birth.

In patients who suffer frequent, severe, prolonged attacks, inhaled salbutamol has been shown in some studies to reduce their duration.

The use of botulinum toxin has been proposed as analgesic, and low dose diazepam at bedtime has been suggested as preventative.

The most common approach for mild cases is simply reassurance and topical treatment with calcium-channel blocker (diltiazem, nifedipine) ointment, salbutamol inhalation and sublingual nitroglycerine.For persistent cases, local anesthetic blocks, clonidine or Botox injections can be considered. Supportive treatments directed at aggravating factors include high-fiber diet, withdrawal of drugs which have gut effects (e.g., drugs that provoke or worsen constipation including narcotics and oral calcium channel blockers; drugs that provoke or worsen diarrhea including quinidine, theophylline, and antibiotics), warm baths, rectal massage, perineal strengthening exercises, anti-cholinergic agents, non-narcotic analgesics, sedatives or muscle relaxants such as diazepam.

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common.

Hereditary sensory neuropathy type IV (HSN4) is a rare genetic disorder characterized by the loss of sensation (sensory loss), especially in the feet and legs and, less severely, in the hands and forearms. The sensory loss is due to abnormal functioning of small, unmyelinated nerve fibers and portions of the spinal cord that control responses to pain and temperature as well as other involuntary or automatic body processes. Sweating is almost completely absent with this disorder. Intellectual disability is usually present.

Type 4, congenital insensitivity to pain with anhidrosis (CIPA), is an autosomal recessive condition and affected infants present with episodes of hyperthermia unrelated to environmental temperature, anhidrosis and insensitivity to pain. Palmar skin is thickened and charcot joints are commonly present. NCV shows motor and sensory nerve action potentials to be normal. The histopathology of peripheral nerve biopsy reveals absent small unmyelinated fibers and mitochondria are abnormally enlarged.

Management of Hereditary sensory and autonomic neuropathy Type 4:

Treatment of manifestations: Treatment is supportive and is best provided by specialists in pediatrics, orthopedics, dentistry, ophthalmology, and dermatology. For anhidrosis: Monitoring body temperature helps to institute timely measures to prevent/manage hyperthermia or hypothermia. For insensitivity to pain: Modify as much as reasonable a child’s activities to prevent injuries. Inability to provide proper immobilization as a treatment for orthopedic injuries often delays healing; additionally, bracing and invasive orthopedic procedures increase the risk for infection. Methods used to prevent injuries to the lips, buccal mucosa, tongue, and teeth include tooth extraction, and/or filing (smoothing) of the sharp incisal edges of teeth, and/or use of a mouth guard. Skin care with moisturizers can help prevent palmar and plantar hyperkeratosis and cracking and secondary risk of infection; neurotrophic keratitis is best treated with routine care for dry eyes, prevention of corneal infection, and daily observation of the ocular surface. Interventions for behavioral, developmental, and motor delays as well as educational and social support for school-age children and adolescents are recommended.

Prevention of secondary complications: Regular dental examinations and restriction of sweets to prevent dental caries; early treatment of dental caries and periodontal disease to prevent osteomyelitis of the mandible. During and following surgical procedures, potential complications to identify and manage promptly include hyper- or hypothermia and inadequate sedation, which may trigger unexpected movement and result in secondary injuries.

Definitive diagnosis is made by suction biopsy of the distally narrowed segment. A histologic examination of the tissue would show a lack of ganglionic nerve cells. Diagnostic techniques involve anorectal manometry, barium enema, and rectal biopsy.

The suction rectal biopsy is considered the current international gold standard in the diagnosis of Hirschsprung's disease.

Radiologic findings may also assist with diagnosis. Cineanography (fluoroscopy of contrast medium passing anorectal region) assists in determining the level of the affected intestines.

Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation.

They are less common than Charcot-Marie-Tooth disease.

A team from the National Institute of Nutrition, Hyderabad conducted research in the affected regions and found out that the disease was confined to a dalit colony. They also found out that the disease was affecting people of all age groups and it was non-contagious and non-infectious. This research was further followed by research conducted over four years (1984–88) by the Indian Council of Medical Research (ICMR). Study groups involving experts from different medical fields were formed and these groups visited the affected places to conduct experiments. They were also helped by the Health Department of Karnataka who also provided a team to assist them. Despite undertaking extensive research, the team could not come into any conclusion on the cause of the disease. The team wound up in 1988 and this was the first phase of their research. The second phase of the research by ICMR was started in the year 2001 under the leadership of S. S. Agarwal of the Sanjay Gandhi Post-graduate centre in Lucknow. Some of the activities in the second phase were to x-ray the patients and also study their family history to see if the disease was related to genetics. The study reported that Handigodu syndrome is a syndrome of familial spondyloepi(meta)physeal dysplasia. It is inherited as an autosomal dominant trait. All the presentations of the varied manifestation of the disease could be explained as being caused by defective development of bones as a result of monogenic disorder.

Symptoms of the disease are an acute pain and swelling in the hips and knee joints. Some of the other characteristics of this disease are dwarfism from birth, deformation of the limbs after age seven and death as early as between 25 and 30 years or even younger. Depending on the mobility of the affected patients, the disease has been identified with three severities: in mild to moderate cases, the patient is able to walk with difficulty, in severe cases mobility is very restricted, whereas in acute cases the limbs are bent and badly crippled making the patients crawl.

Diagnosis is by rectal examination. A specialized tool called a "Perineocaliper" can be used to measure the descent of the perineum. A retro anal ultrasound scan may demonstrate the condition. "Anti sagging tests", whereby the abnormal descent is corrected temporarily, may help to show whether symptoms are due to descending perineum syndrome or are in fact due to another condition.

Normally, the anal margin lies just below a line drawn between the coccyx (tailbone) and the pubic symphysis. In descending perineum syndrome the anal canal is situated several cm below this imaginary line, or it descends 3–4 cm during straining.

Defecography may also demonstrate abnormal perineal descent.

Physical examination can rule out anismus (by identifying another cause) but is not sufficient to diagnose anismus.

The rectal cooling test is suggested to differentiate between rectal inertia and impaired relaxation/paradoxical contraction

Other techniques include manometry, balloon expulsion test, evacuation proctography (see defecating proctogram), and MRI defecography. Diagnostic criteria are: fulfillment of criteria for functional constipation, manometric and/or EMG and/or radiological evidence (2 out of 3), evidence of adequate expulsion force, and evidence of incomplete evacuation. Recent dynamic imaging studies have shown that in persons diagnosed with anismus the anorectal angle during attempted defecation is abnormal, and this is due to abnormal (paradoxical) movement of the puborectalis muscle.

Treatment of Hirschsprung's disease consists of surgical removal (resection) of the abnormal section of the colon, followed by reanastomosis.

Surgical treatments may be used to treat the condition, and include retro-rectal levatorplasty, post-anal repair, retro-anal levator plate myorrhaphy.

Levator ani syndrome is a condition characterized by brief intermittent burning pain or tenesmus of the rectal or perineal area.

Pain relief is administered concomitantly to the treatment of the primary disease causing tenesmus. Methadone has been shown to be an effective pain-reliever.

Familial LPL deficiency should be considered in anyone with severe hypertriglyceridemia and the chylomicronemia syndrome. The absence of secondary causes of severe hypertriglyceridemia (like e.g. diabetes, alcohol, estrogen-, glucocorticoid-, antidepressant- or isotretinoin-therapy, certain antihypertensive agents, and paraproteinemic disorders) increases the possibility of LPL deficiency. In this instance besides LPL also other loss-of-function mutations in genes that regulate catabolism of triglyceride-rich lipoproteins (like e.g. ApoC2, ApoA5, LMF-1, GPIHBP-1 and GPD1) should also be considered

The diagnosis of familial lipoprotein lipase deficiency is finally confirmed by detection of either homozygous or compound heterozygous pathogenic gene variants in "LPL" with either low or absent lipoprotein lipase enzyme activity.

Lipid measurements

· Milky, lipemic plasma revealing severe hyperchylomicronemia;

· Severely elevated fasting plasma triglycerides (>2000 mg/dL);

LPL enzyme

· Low or absent LPL activity in post-heparin plasma;

· LPL mass level reduced or absent in post-heparin plasma;

Molecular genetic testing

The LPL gene is located on the short (p) arm of chromosome 8 at position 22. More than 220 mutations in the LPL gene have been found to cause familial lipoprotein lipase deficiency so far.

With most infections, the key is to block the spread of the organism.

- Wash hands frequently

- Eat properly prepared and stored food.

- Bleach soiled laundry

- Vaccinations for "Vibrio cholerae" and rotavirus have been developed. Rotavirus vaccination is recommended for infants in the U.S. Vaccines for "V. cholerae" may be administered to individuals traveling to at-risk areas

A physical examination should involve at least an abdominal exam and rectal exam. Abdominal exam may reveal an abdominal mass if there is significant stool burden and may reveal abdominal discomfort. Rectal examination gives an impression of the anal sphincter tone and whether the lower rectum contains any feces or not. Rectal examination also gives information on the consistency of the stool, the presence of hemorrhoids, blood and whether any perineal irregularities are present including skin tags, fissures, anal warts. Physical examination is done manually by a physician and is used to guide which diagnostic tests to order.

Functional constipation is common and does not warrant diagnostic testing. Imaging and laboratory tests are typically recommended for those with alarm signs or symptoms.

The laboratory tests performed depends on the suspected underlying cause of the constipation. Tests may include CBC (complete blood count), thyroid function tests, serum calcium, serum potassium, etc.

Abdominal X-rays are generally only performed if bowel obstruction is suspected, may reveal extensive impacted fecal matter in the colon, and may confirm or rule out other causes of similar symptoms.

Colonoscopy may be performed if an abnormality in the colon like a tumor is suspected. Other tests rarely ordered include anorectal manometry, anal sphincter electromyography, and defecography.

Colonic propagating pressure wave sequences (PSs) are responsible for discrete movements of the bowel contents and are vital for normal defecation. Deficiencies in PS frequency, amplitude, and extent of propagation are all implicated in severe defecatory dysfunction (SDD). Mechanisms that can normalize these aberrant motor patterns may help rectify the problem. Recently the novel therapy of sacral nerve stimulation (SNS) has been utilized for the treatment of severe constipation.

There is a risk of development of cancer with fundic gland polyposis, but it varies based on the underlying cause of the polyposis. The risk is highest with congenital polyposis syndromes, and is lowest in acquired causes. As a result, it is recommended that patients with multiple fundic polyps have a colonoscopy to evaluate the colon. If there are polyps seen on colonoscopy, genetic testing and testing of family members is recommended.

In the gastric adenocarcinoma associated with proximal polyposis of the stomach (GAPPS), there is a high risk of early development of proximal gastric adenocarcinoma.

It is still unclear which patients would benefit with surveillance gastroscopy, but most physicians recommend endoscopy every one to three years to survey polyps for dysplasia or cancer. In the event of high grade dysplasia, polypectomy, which is done through the endoscopy, or partial gastrectomy may be recommended. One study showed the benefit of NSAID therapy in regression of gastric polyps, but the efficacy of this strategy (given the side effects of NSAIDs) is still dubious.

Identification of the exact causes usually begins with a thorough medical history, including detailed questioning about symptoms, bowel habits, diet, medication and other medical problems. Digital rectal examination is performed to assesses resting pressure and voluntary contraction (maximum squeeze) of the sphincter complex and puborectalis. Anal sphincter defects, rectal prolapse, and abnormal perineal descent may be detected. Anorectal physiology tests assess the functioning of the anorectal anatomy. Anorectal manometry records the pressure exerted by the anal sphincters and puborectalis during rest and during contraction. The procedure is also able to assess sensitivity of the anal canal and rectum. Anal electromyography tests for nerve damage, which is often associated with obstetric injury. Pudendal nerve terminal motor latency tests for damage to the pudendal motor nerves. Proctography, also known as defecography, shows how much stool the rectum can hold, how well the rectum holds it, and how well the rectum can evacuate the stool. It will also highlight defects in the structure of the rectum such as internal rectal intussusception. Dynamic pelvic MRI, also called MRI defecography is an alternative which is better for some problems but not as good for other problems. Proctosigmoidoscopy involves the insertion of an endoscope (a long, thin, flexible tube with a camera) into the anal canal, rectum and sigmoid colon. The procedure allows for visualization of the interior of the gut, and may detect signs of disease or other problems that could be a cause, such as inflammation, tumors, or scar tissue. Endoanal ultrasound, which some consider to be the gold standard for detection of anal canal lesions, evaluates the structure of the anal sphincters, and may detect occult sphincter tears that otherwise would go unseen.

Functional FI is common. The Rome process published diagnostic criteria for functional FI, which they defined as "recurrent uncontrolled passage of fecal material in an individual with a developmental age of at least 4 years". The diagnostic criteria are, one or more of the following factors present for the last 3 months: abnormal functioning of normally innervated and structurally intact muscles, minor abnormalities of sphincter structure/innervation (nerve supply), normal or disordered bowel habits, (i.e., fecal retention or diarrhea), and psychological causes. Furthermore, exclusion criteria are given. These are factors which all must be excluded for a diagnosis of functional FI, and are abnormal innervation caused by lesion(s) within the brain (e.g., dementia), spinal cord (at or below T12), or sacral nerve roots, or mixed lesions (e.g., multiple sclerosis), or as part of a generalized peripheral or autonomic neuropathy (e.g., due to diabetes), anal sphincter abnormalities associated with a multisystem disease (e.g., scleroderma), and structural or neurogenic abnormalities that are the major cause.

Most juvenile polyps are benign, however, malignancy can occur. The cumulative lifetime risk of colorectal cancer is 39% in patients with juvenile polyposis syndrome.