No specific treatment or cure exists. Affected children usually need total parenteral nutrition through a central venous catheter. Further worsening of liver damage should however be avoided if possible. Diarrhea will likely continue even though food stops passing through the gastrointestinal system. They can subsequently be managed with tube feeding, and some may be weaned from nutritional support during adolescence.

There is no known cure at the moment but there are several things that can be done to relieve the symptoms. Moisturising products are very helpful to minimize the scaling/cracking, and anti-infective treatments are useful when appropriate because the skin is very susceptible to infection. Extra protein in the diet during childhood is also beneficial, to replace that which is lost through the previously mentioned "leaky" skin.

Steroid and retinoid products have been proven ineffective against Netherton syndrome, and may in fact make things worse for the affected individual.

Intravenous immunoglobulin has become established as the treatment of choice in Netherton's syndrome. This therapy reduces infection; enables improvement and even resolution of the skin and hair abnormalities, and dramatically improves quality of life of the patients; although exactly how it achieves this is not known. Given this; it is possible that the reason Netherton's usually is not very severe at or shortly after birth is due to a protective effect of maternal antibodies; which cross the placenta but wane by four to six months.

The standard treatment is chenodeoxycholic acid (CDCA) replacement therapy. Serum cholesterol levels are also followed. If hypercholesterolemia is not controlled with CDCA, an HMG-CoA reductase inhibitor ("statins" such as simvastatin) can also be used.

The only treatment for Omenn syndrome is chemotherapy followed by a bone marrow transplantation. Without treatment, it is rapidly fatal in infancy.

Acrodermatitis enteropathica without treatment is fatal, and affected individuals may die within a few years. There is no cure for the condition. Treatment includes lifelong dietary zinc supplementation.

Most patients with hyper IgE syndrome are treated with long-term antibiotic therapy to prevent staphylococcal infections. Good skin care is also important in patients with hyper IgE syndrome. High-dose intravenous gamma-globulin has also been suggested for the treatment of severe eczema in patients with HIES and atopic dermatitis.

Currently, there is no cure for infantile Refsum disease syndrome, nor is there a standard course of treatment. Infections should be guarded against to prevent such complications as pneumonia and respiratory distress. Other treatment is symptomatic and supportive. Patients show variable lifespans with some individuals surviving until adulthood and into old age.

It is nearly always fatal unless, like short bowel syndrome patients, treated with parenteral nutrition or an intestinal transplant. The patient is often classified as being in "intestinal failure" and treated with the cohort of patients known as "short bowel syndrome" patients.

Treatment is limited. Drugs can alleviate the symptoms, such as sleep difficulties and epilepsy. Physiotherapy helps affected children retain the ability to remain upright for as long as possible, and prevents some of the pain.

Recent attempts to treat INCL with cystagon have been unsuccessful.

Standard of care for treatment of CPT II deficiency commonly involves limitations on prolonged strenuous activity and the following dietary stipulations:

- The medium-chain fatty acid triheptanoin appears to be an effective therapy for adult-onset CPT II deficiency.

- Restriction of lipid intake

- Avoidance of fasting situations

- Dietary modifications including replacement of long-chain with medium-chain triglycerides supplemented with L-carnitine

On April 27, 2017, the U.S. Food and Drug Administration approved Brineura (cerliponase alfa) as the first specific treatment for NCL. Brineura is enzyme replacement therapy manufactured through recombinant DNA technology. The active ingredient in Brineura, cerliponase alpha, is intended to slow loss of walking ability in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency. Brineura is administered into the cerebrospinal fluid by infusion via a surgically implanted reservoir and catheter in the head (intraventricular access device).

There are no specific treatments for lipid storage disorders; however, there are some highly effective enzyme replacement therapies for people with type 1 Gaucher disease and some patients with type 3 Gaucher disease. There are other treatments such as the prescription of certain drugs like phenytoin and carbamazepine to treat pain for patients with Fabry disease. Furthermore, gene thereapies and bone marrow transplantation may prove to be effective for certain lipid storage disorders. Diet restrictions do not help prevent the buildup of lipids in the tissues.

On October 20, 2005, the Food and Drug Administration approved a phase I clinical trial of neural stem cells to treat infantile and late infantile Batten disease. Subsequent approval from an independent review board also approved the stem cell therapy in early March 2006. This treatment will be the first ever transplant of fetal stem cells performed on humans. The therapy is being developed by Stem Cells Inc and is estimated to have six patients. The treatment will be carried out in Oregon.

Juvenile NCL has recently been listed on the Federal Clinical Trials website to test the effectiveness of bone marrow/stem cell transplants for this condition. A bone marrow transplant has been attempted in the late infantile form of NCL with disappointing results; while the transplant may have slowed the onset of the disease, the child eventually developed the disease and died in 1998.

Trials testing the effectiveness of bone marrow transplants for infantile NCL in Finland have also been disappointing, with only a slight slowing of disease reported.

No cures for lysosomal storage diseases are known, and treatment is mostly symptomatic, although bone marrow transplantation and enzyme replacement therapy (ERT) have been tried with some success. ERT can minimize symptoms and prevent permanent damage to the body. In addition, umbilical cord blood transplantation is being performed at specialized centers for a number of these diseases. In addition, substrate reduction therapy, a method used to decrease the production of storage material, is currently being evaluated for some of these diseases. Furthermore, chaperone therapy, a technique used to stabilize the defective enzymes produced by patients, is being examined for certain of these disorders. The experimental technique of gene therapy may offer cures in the future.

Ambroxol has recently been shown to increase activity of the lysosomal enzyme glucocerebrosidase, so it may be a useful therapeutic agent for both Gaucher disease and Parkinson's disease. Ambroxol triggers the secretion of lysosomes from cells by inducing a pH-dependent calcium release from acidic calcium stores. Hence, relieving the cell from accumulating degradation products is a proposed mechanism by which this drug may help.

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).

In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others.

Medical treatments include the use of hyperbaric oxygen which has beneficial effects in radiation proctitis or anal damage. Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and vitamin B12 or vitamin D supplements, together with bile acid sequestrants for bile acid diarrhea and possibly antibiotics for small intestinal bacterial overgrowth. Probiotics have all been suggested as another therapeutic avenue.

Endoscopic therapies including argon plasma coagulation have been used for bleeding telangiectasia in radiation proctitis and at other intestinal sites, although there is a rick of perforation. Sucralfate enemas look promising in proctitis.

Surgical treatment may be needed for intestinal obstruction, fistulae, or perforation, which can happen in more severe cases. These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common.

Optimal treatment usually produces significant improvements in quality of life.

Treatment is multifactorial. A diet very low in fat and high in high quality protein is essential. Treatment of humans can also involve the use of MCT (medium-chain triglycerides) oil and/or the drug octreotide. In dogs, fat soluble vitamins (A, D, E, and K) should be supplemented. Corticosteroid treatment may be required for life. Antibiotics can be used to treat bacterial overgrowth. With a very low serum albumin, transfusion with blood plasma or an infusion of hetastarch may be necessary to treat the signs until the diet can take effect. Lymphangiectasia is rarely cured but can remain in remission for a long time. It can be fatal when unresponsive to treatment.

Although there is no known cure for Krabbe disease, bone marrow transplantation has been shown to benefit cases early in the course of the disease. Generally, treatment for the disorder is symptomatic and supportive. Physical therapy may help maintain or increase muscle tone and circulation. Cord blood transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.

Treatment for colitis-X usually does not save the horse. The prognosis is average to poor, and mortality is 90% to 100%. However, treatments are available, and one famous horse that survived colitis-X was U.S. Triple Crown winner Seattle Slew, that survived colitis-X in 1978 and went on to race as a four-year-old.

Large amounts of intravenous fluids are needed to counter the severe dehydration, and electrolyte replacement is often necessary. Flunixin meglumine (Banamine) may help block the effects of toxemia. Mortality rate has been theorized to fall to 75% if treatment is prompt and aggressive, including administration of not only fluids and electrolytes, but also blood plasma, anti-inflammatory and analgesic drugs, and antibiotics. Preventing dehydration is extremely important. Nutrition is also important. Either parenteral or normal feeding can be used to support the stressed metabolism of the sick horse. Finally, the use of probiotics is considered beneficial in the restoration of the normal intestinal flora. The probiotics most often used for this purpose contain "Lactobacillus" and "Bifidobacterium".

Improving environmental factors will reduce damage to the hair. Gentle brushing with a soft brush should replace more aggressive brushing, ratting, or other procedures. Harsh chemicals such as hair straightening compounds and permanents should be avoided. The hair should not be ironed. Excessively harsh shampoo should be avoided. Hair conditioners should be used.

Dysentery is managed by maintaining fluids by using oral rehydration therapy. If this treatment cannot be adequately maintained due to vomiting or the profuseness of diarrhea, hospital admission may be required for intravenous fluid replacement. In ideal situations, no antimicrobial therapy should be administered until microbiological microscopy and culture studies have established the specific infection involved. When laboratory services are not available, it may be necessary to administer a combination of drugs, including an amoebicidal drug to kill the parasite, and an antibiotic to treat any associated bacterial infection.

If shigellosis is suspected and it is not too severe, letting it run its course may be reasonable — usually less than a week. If the case is severe, antibiotics such as ciprofloxacin or TMP-SMX may be useful. However, many strains of "Shigella" are becoming resistant to common antibiotics, and effective medications are often in short supply in developing countries. If necessary, a doctor may have to reserve antibiotics for those at highest risk for death, including young children, people over 50, and anyone suffering from dehydration or malnutrition.

Amoebic dysentery is often treated with two antimicrobial drug such as metronidazole and paromomycin or iodoquinol.

There is currently no cure or standard procedure for treatment. A bone marrow transplant has been attempted on a child, but it made no improvement. Hydrocephalus may be seen in younger patients and can be relieved with surgery or by implanting a shunt to relieve pressure.

As of October 2015, asfotase alfa (Strensiq) has been approved by the FDA for the treatment of hypophosphatasia. Current management consists of palliating symptoms, maintaining calcium balance and applying physical, occupational, dental and orthopedic interventions, as necessary.

- Hypercalcemia in infants may require restriction of dietary calcium or administration of calciuretics. This should be done carefully so as not to increase the skeletal demineralization that results from the disease itself. Vitamin D sterols and mineral supplements, traditionally used for rickets or osteomalacia, should not be used unless there is a deficiency, as blood levels of calcium ions (Ca2+), inorganic phosphate (Pi) and vitamin D metabolites usually are not reduced.

- Craniosynostosis, the premature closure of skull sutures, may cause intracranial hypertension and may require neurosurgical intervention to avoid brain damage in infants.

- Bony deformities and fractures are complicated by the lack of mineralization and impaired skeletal growth in these patients. Fractures and corrective osteotomies (bone cutting) can heal, but healing may be delayed and require prolonged casting or stabilization with orthopedic hardware. A load-sharing intramedullary nail or rod is the best surgical treatment for complete fractures, symptomatic pseudofractures, and progressive asymptomatic pseudofractures in adult hypophosphatasia patients.

- Dental problems: Children particularly benefit from skilled dental care, as early tooth loss can cause malnutrition and inhibit speech development. Dentures may ultimately be needed. Dentists should carefully monitor patients’ dental hygiene and use prophylactic programs to avoid deteriorating health and periodontal disease.

- Physical Impairments and pain: Rickets and bone weakness associated with hypophosphatasia can restrict or eliminate ambulation, impair functional endurance, and diminish ability to perform activities of daily living. Nonsteroidal anti-inflammatory drugs may improve pain-associated physical impairment and can help improve walking distance]

- Bisphosphonate (a pyrophosphate synthetic analog) in one infant had no discernible effect on the skeleton, and the infant’s disease progressed until death at 14 months of age.

- Bone marrow cell transplantation in two severely affected infants produced radiographic and clinical improvement, although the mechanism of efficacy is not fully understood and significant morbidity persisted.

- Enzyme replacement therapy with normal, or ALP-rich serum from patients with Paget’s bone disease, was not beneficial.

- Phase 2 clinical trials of bone targeted enzyme-replacement therapy for the treatment of hypophosphatasia in infants and juveniles have been completed, and a phase 2 study in adults is ongoing.

Prevention of radiation injury to the small bowel is a key aim of techniques such as brachytherapy, field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy. Medications including ACE inhibitors, statins and probiotics have also been studied and reviewed.

As of 2010 there was no treatment that addressed the cause of Tay–Sachs disease or could slow its progression; people receive supportive care to ease the symptoms and extend life by reducing the chance of contracting infections. Infants are given feeding tubes when they can no longer swallow. In late-onset Tay–Sachs, medication (e.g., lithium for depression) can sometimes control psychiatric symptoms and seizures, although some medications (e.g., tricyclic antidepressants, phenothiazines, haloperidol, and risperidone) are associated with significant adverse effects.