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.

The most common method to manage hypoglycemia and diabetes is with an insulin pump. . However in infants and very young children long acting insulins like Glargine and Levemir are preferred to prevent recurrent hypoglycemia . As soon as parent knows Walcott-Rallison syndrome is the source, treatment or therapy plans need to be drawn up along with frequent check ins to make sure kidney and liver functions are around normal and insulin therapy are working. If needed, the patient can undergo thyroxin therapy in order to maintain proper thyroid stimulating hormone levels. This has only been needed in a few cases were hypothyroidism was present in the patient.

There is currently no cure for Costeff syndrome. Treatment is supportive, and thus focuses on management of the symptoms. The resulting visual impairment, spasticity, and movement disorders are treated in the same way as similar cases occurring in the general population.

There are no treatments for MDDS, but some of the symptoms can be managed. For survivors living with MDDS, there are drugs to control epilepsy, and physical therapy can help with muscle control. Liver transplants may benefit people with liver involvement.

Nucleoside bypass therapy is an experimental treatment aimed to restore the normal levels of deoxyribonucleotides (dNTPs) in mitochondria.

Individuals presenting with Type III galactosemia must consume a lactose- and galactose-restricted diet devoid of dairy products and mucilaginous plants. Dietary restriction is the only current treatment available for GALE deficiency. As glycoprotein and glycolipid metabolism generate endogenous galactose, however, Type III galactosemia may not be resolved solely through dietary restriction.

There is no cure for Alström syndrome; however, there are treatment aims to reduce the symptoms and prevent further complications. Some of these treatment aims include:

- Corrective lenses: tinted lenses that help with the sensitivity from bright lights. The patients may have to adapt to reading in Braille, use adaptive equipment, mobility aids, and adaptive computing skills.

- Education: patients with Alström syndrome suffering from intellectual disabilities must have access to education. They must be able to receive free and appropriate education. Some Alström syndrome patients are educated in normal classrooms. Other patients have to take special education classes or attend to specialized schools that are prepared to teach children with disabilities. Staff members from schools have to consult with patient's parents or caregivers in order to design an education plan based on the child's needs. In addition, the school may document the progress of the child in order to confirm that the child's needs are being met.

- Hearing aids: the battery-operated devices are available in three styles: behind the ear, in the ear, and inside the ear canal. Behind the ear aims for mild-to-profound hearing loss. In the ear aims for mild to severe hearing loss. Lastly, the canal device is aimed for mild to moderately severe hearing loss. Patients that have severe hearing loss may benefit from a cochlear implant.

- Diet: an appropriate and healthy diet is necessary for individuals with Alström syndrome because it could potentially decreases chances of obesity or diabetes.

- Occupational therapy: the therapist helps the child learn skills to help him or her perform basic daily tasks like eating, getting dressed, and communicating with others.

- Physical Activity: exercising reduces chances of being obese and helping control blood sugar levels.

- Dialysis: helps restore filtering function. With hemodialysis, a patient's blood circulates into an external filter and clean. The filtered blood is then returned into the body. With peritoneal dialysis, fluid containing dextrose is introduced into the abdomen by a tube. The solution then absorbs the wastes into the body and is then removed.

- Transplantation: patients that endure a kidney failure may undergo a kidney transplantation.

- Surgery: if the patient endures severe scoliosis or kyphosis, surgery may be required.

The long-term prognosis of Costeff syndrome is unknown, though it appears to have no effect on life expectancy at least up to the fourth decade of life. However, as mentioned previously, movement problems can often be severe enough to confine individuals to a wheelchair at an early age, and both visual acuity and spasticity tend to worsen over time.

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.

Typically no treatment is needed. If jaundice is significant phenobarbital may be used.

LAL deficiency can be treated with sebelipase alfa is a recombinant form of LAL that was approved in 2015 in the US and EU. The disease of LAL affects < 0.2 in 10,000 people in the EU. According to an estimate by a Barclays analyst, the drug will be priced at about US $375,000 per year.

It is administered once a week via intraveneous infusion in people with rapidly progressing disease in the first six months of life. In people with less aggressive disease, it is given every other week.

Before the drug was approved, treatment of infants was mainly focused on reducing specific complications and was provided in specialized centers. Specific interventions for infants included changing from breast or normal bottle formula to a specialized low fat formula, intravenous feeding, antibiotics for infections, and steroid replacement therapy because of concerns about adrenal function.

Statins were used in people with LAL-D prior to the approval of sebelipase alfa; they helped control cholesterol but did not appear to slow liver damage; liver transplantation was necessary in most patients.

Infants with LAL deficiencies typically show signs of disease in the first weeks of life and if untreated, die within 6–12 months due to multi-organ failure. Older children or adults with LAL-D may remain undiagnosed or be misdiagnosed until they die early from a heart attack or stroke or die suddenly of liver failure. The first enzyme replacement therapy was approved in 2015. In those clinical trials nine infants were followed for one year; 6 of them lived beyond one year. Older children and adults were followed for 36 weeks.

The primary treatment for type 1 tyrosinemia is nitisinone (Orfadin) and restriction of tyrosine in the diet. Nitisinone inhibits the conversion of 4-OH phenylpyruvate to homogentisic acid by 4-Hydroxyphenylpyruvate dioxygenase, the second step in tyrosine degradation. By inhibiting this enzyme, the accumulation of the fumarylacetoacetate is prevented. Previously, liver transplantation was the primary treatment option and is still used in patients in whom nitisinone fails.

As reported by Dispenzieri "et al." Mayo Clinic treatment regimens are tailored to treat the clinical manifestations and prognosis for the rate of progression of the POEMS syndrome in each patient. In rare cases, patients may have minimal or no symptoms at presentation or after successful treatment of their disorder. These patients may be monitored every 2–3 months for symptoms and disease progression. Otherwise, treatment is divided based on the local versus systemic spread of its clonal plasma cells. Patients with one or two plasmacytoma bone lesions and no clonal plasma cells in their bone marrow biopsy specimens are treated by surgical removal or radiotherapy of their tumors. These treatments can relieve many of the syndromes clinical manifestations including neuropathies, have a 10-year overall survival of 70% and a 6-year progression-free survival of 62%. Patients with >2 plasmacytoma bone lesions and/or increases in bone marrow clonal plasma cells are treated with a low-dose or high-dose chemotherapy regimen, i.e. a corticosteroid such as dexamethasone plus an alkylating agents such as melphalan. Dosage regimens are selected on the basis of patient tolerance. Hematological response rates to the dexamethasone/melphalan regimens have been reported to be in the 80% range with neurological response rates approaching 100%. Patients successfully treated with the high-dose dexamethasone/melphalan regimen have been further treated with autologous stem cell transplantation. In 59 patients treated with the chemotherapy/transplantation regimen, the Mayo Clinic reported progression-free survival rates of 98%, 94%, and 75% at 1, 2, and 5 years, respectively.

Other treatment regiments are being studied. Immunomodulatory imide drugs such as thalidomide and lenalidomide have been used in combination with dexamethasone to treat POEMS syndrome patients. While the mechanism of action fo these immunomodulators are not clear, they do inhibit the production of cytokines suspected of contributing to POEMS syndrome such as VEGF, TNFα, and IL-6 and stimulate T cells and NK cells to increase their production of interferon gamma and interleukin 2 (see immunomodulatory imide drug's mechanism of action). A double blind study of 25 POEMS syndrome patients found significantly better results (VEGF reduction, neuromuscular function improvement, quality of life improvement) in patients treated with thalidomide plus dexamethasone compared to patients treated with a thalidomide placebo plus dexamethasone.

Since VEGF plays a central role in the symptoms of POEMS syndrome, some have tried bevacizumab, a monoclonal antibody directed against VEGF. While some reports were positive, others have reported capillary leak syndrome suspected to be the result of overly rapid lowering of VEGF levels. It therefore remains doubtful as to whether this will become part of standard treatment for POEMS syndrome.

Although research is ongoing, treatment options are currently limited; vitamins are frequently prescribed, though the evidence for their effectiveness is limited.

Pyruvate has been proposed in 2007 as a treatment option. N-acetyl cysteine reverses many models of mitochondrial dysfunction.. In the case of mood disorders, specifically bipolar disorder, it is hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options.

Carotenemia and carotenoderma is in itself harmless, and does not require treatment. In primary carotenoderma, when the use of high quantities of carotene is discontinued the skin color will return to normal. It may take up to several months, however, for this to happen. Infants with this condition should not be taken off prescribed vitamin supplements unless advised to do so by the child's pediatrician.

As to underlying disorders in secondary carotinemia and carotenoderma, treatment depends wholly on the cause.

MRI will help with the diagnosis of structural abnormality of the brain. Genetic testing may also be pursued.

DeSanctis–Cacchione syndrome is an extremely rare disorder characterized by the skin and eye symptoms of xeroderma pigmentosum (XP) occurring in association with microcephaly, progressive mental retardation, retarded growth and sexual development, deafness, choreoathetosis, ataxia and quadriparesis.

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).

Wolcott–Rallison syndrome, WRS, is a rare, autosomal recessive disorder with infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, osteopenia, mental retardation or developmental delay, and hepatic and renal dysfunction as main clinical findings. Patients with WRS have mutations in the EIF2AK3 gene, which encodes the pancreatic eukaryotic translation initiation factor 2-alpha kinase 3.

The most common drug used to treat AHC is flunarizine. Flunarizine functions by acting as a calcium channel blocker. Other drugs, in order of frequency of use are benzodiazepines, carbamazapine, barbiturates, and valproic acid. Flunarizine is prescribed for the purpose of reducing the severity of AHC attacks and the number of episodes, though it rarely stops attacks altogether. Minimizing the attacks may help reduce damage to the body from hemiplegic attacks and improve long-term outcomes as far as mental and physical disabilities are concerned.

Experts differ in their confidence in flunarizine's effectiveness. Some studies have found it to be very effective in reducing the duration, severity, and frequency of hemiplegic attacks. It is generally considered the best treatment available, but this drug is thought by some to be of little benefit to AHC patients. Many patients suffer adverse effects without seeing any improvement. Flunarizine also causes problems because it is difficult for patients to obtain, as it is not readily available in the United States.

Where venesection is not possible, long-term administration of desferrioxamine mesylate is useful. Desferrioxamine is an iron-chelating compound, and excretion induced by desferrioxamine is enhanced by administration of Vitamin C. It cannot be used during pregnancy or breast-feeding due to risk of defects in the child.

The best treatment for MAS has not been firmly established. Most commonly used treatments include high-dose glucocorticoids, and cyclosporine. In refractory cases treatment regimens are used similar to that in HLH.

In at least some case, the gene lesion involves a mutation in the "CSB" gene.

It can be associated with "ERCC6".

Most pharmacological treatments work poorly, but the best treatment is a low dosage of clonazepam, a muscle relaxant. Patients may also benefit from other benzodiazepines, phenobarbital, and other anticonvulsants such as valproic acid. Affected individuals have reported garlic to be effective for softening the attacks, but no studies have been done on this.