The prognosis of this condition in childhood usually has a stable outcome, whereas in neonatal is almost always fatal, according to Jurecka, et al.

As of June 2014 (the latest update on HFM in GeneReviews) a total of 32 families had been reported with a clinical diagnosis of HFM of which there was genotypic confirmation in 24 families. Since then, another two confirmed cases have been reported and an additional case was reported based on a clinical diagnosis alone. Most cases emerge from consanguineous parents with homozygous mutations. There are three instances of HFM from non-consanguineous parents in which there were heterozygous mutations. HFM cases are worldwide with mostly private mutations. However, a number of families of Puerto Rican ancestry have been reported with a common pathogenic variant at a splice receptor site resulting in the deletion of exon 3 and the absence of transport function. A subsequent population-based study of newborn infants in Puerto Rico identified the presence of the same variant on the island. Most of the pathogenic variants result in a complete loss of the PCFT protein or point mutations that result in the complete loss of function. However, residual function can be detected with some of the point mutants.

The drug tafamidis has completed a phase II/III 18-month-long placebo controlled clinical trial

and these results in combination with an 18-month follow-on study demonstrated that Tafamidis or Vyndaqel slowed progression of FAP, particularly when administered to patients early in the course of FAP. This drug is now approved by the European Medicines Agency.

The US Food and Drug Administration's Peripheral and Central Nervous System Drugs Advisory Committee rejected the drug in June 2012, in a 13-4 vote. The committee stated that there was not enough evidence supporting efficacy of the drug, and requested additional clinical trials.

Treatment of adenylosuccinate lyase deficiency can be done via epilepsy management with anticonvulsive drugs.Additionally the following options include:

- D-ribose and uridine administration

- Ketogenic diet

- S-adenosyl-l-methionine

Because HFM is a rare disorder, there are no studies that define its optimal treatment. Correction of the systemic folate deficiency, with the normalization of folate blood levels, is easily achieved with high doses of oral folates or much smaller doses of parenteral folate. This will rapidly correct the anemia, immune deficiency and GI signs. The challenge is to achieve adequate treatment of the neurological component of HFM. It is essential that the folate dose is sufficiently high to achieve CSF folate levels as close as possible to the normal range for the age of the child. This requires close monitoring of the CSF folate level. The physiological folate is 5-methyltetrahydrofolate but the oral formulation available is insufficient for treatment of this disorder and a parenteral form is not available. The optimal folate at this time is 5-formyltetrahydrofolate which, after administration, is converted to 5-methyltetrahydrofolate. The racemic mixture of 5-formyltetrahydrofolate (leucovorin) is generally available; the active S-isomer, levoleucovorin, may be obtained as well. Parenteral administration is the optimal treatment if that is possible. Folic acid should not be used for the treatment of HFM. Folic acid is not a physiological folate. It binds tightly to, and may impede, FRα-mediated endocytosis which plays an important role in the transport of folates across the choroid plexus into the CSF (see above). For a further consideration of treatment see GeneReviews.

Prevention focuses on improving sanitation of water and food sources.

Treatment focuses on addressing the central components of intestinal inflammation, bacterial overgrowth and nutritional supplementation.

In the absence of a liver transplant, FAP is invariably fatal, usually within a decade. The disadvantage of liver transplantation is that approximately 10% of the subjects die from the procedure or complications resulting from the procedure, which is a form of gene therapy wherein the liver expressing wild type and mutant TTR is replaced by a liver only expressing wild type TTR. Moreover, transplanted patients must take immune suppressants (drugs) for the remainder of their life, which can lead to additional complications. In late 2011, the European Medicines Agency approved the transthyretin kinetic stabilizer Tafamidis or Vyndaqel discovered by Jeffery W. Kelly and developed by FoldRx pharmaceuticals (acquired by Pfizer in 2010) for the treatment of FAP based on clinical trial data. Tafamidis (20 mg once daily) slowed the progression of FAP over a 36-month period and importantly reversed the weight loss and muscle wasting associated with disease progression.

There are multiple large-field, multi-country research initiatives focusing on strategies to prevent and treat EE.

- The MAL-ED project

- The Alive and Thrive nutrition project

- The Sanitation, Hygiene and Infant Nutrition Efficacy (SHINE) Trial (ClinicalTrials.gov identifier: NCT01824940)

- The WASH Benefits Study

Since the essential pathology is due to the inability to absorb vitamin B from the bowels, the solution is therefore injection of IV vitamin B. Timing is essential, as some of the side effects of vitamin B deficiency are reversible (such as RBC indices, peripheral RBC smear findings such as hypersegmented neutrophils, or even high levels of methylmalonyl CoA), but some side effects are irreversible as they are of a neurological source (such as tabes dorsalis, and peripheral neuropathy). High suspicion should be exercised when a neonate, or a pediatric patient presents with anemia, proteinuria, sufficient vitamin B dietary intake, and no signs of pernicious anemia.

The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e.g., heart attack).

Fructose and fructans are FODMAPs (fermentable oligo-, di- and mono-saccharides and polyols) known to cause gastrointestinal discomfort in susceptible individuals. A low FODMAP diet has widespread application for managing functional gastrointestinal disorders such as IBS.

Whether MTHFR deficiency has any effect at all on all-cause mortality is unclear. One Dutch study showed that the MTHFR mutation was more prevalent in younger individuals (36% relative to 30%), and found that elderly men with MTHFR had an elevated mortality rate, attributable to cancer. Among women, however, no difference in life expectancy was seen. More recently, however, a meta-analysis has shown that overall cancer rates are barely increased with an odds ratio of 1.07, which suggests that an impact on mortality from cancer is small or zero.

Low-protein food is recommended for this disorder, which requires food products low in particular types of amino acids (e.g., methionine).

The first line of treatment are corticosteroids and other medicines used to suppress the immune system such as tacrolimus and sirolimus.

A intravenous nutrition such as total parenteral nutrition and/or a special diet may be necessary. Hematopoietic stem cell transplantation may be curative.

Patients with propionic acidemia should be started as early as possible on a low protein diet. In addition to a protein mixture that is devoid of methionine, threonine, valine, and isoleucine, the patient should also receive -carnitine treatment and should be given antibiotics 10 days per month in order to remove the intestinal propiogenic flora. The patient should have diet protocols prepared for him with a “well day diet” with low protein content, a “half emergency diet” containing half of the protein requirements, and an “emergency diet” with no protein content. These patients are under the risk of severe hyperammonemia during infections that can lead to comatose states.

Liver transplant is gaining a role in the management of these patients, with small series showing improved quality of life.

Reoviruses vaccines are advocated (in dams or in broilers) do not entirely solve the problem.

General hygiene and correct breeding conditions (especially correct brooding temperatures) may be efficient, but the disease often disappears as it had appeared, which makes it difficult to appreciate the effectiveness of control measures.

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.

Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) is a rare autosomal recessive mitochondrial disease. It has been previously referred to as polyneuropathy, ophthalmoplegia, leukoencephalopathy, and POLIP syndrome. The disease presents in childhood, but often goes unnoticed for decades. Unlike typical mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations, MNGIE is caused by mutations in the TYMP gene, which encodes the enzyme thymidine phosphorylase. Mutations in this gene result in impaired mitochondrial function, leading to intestinal symptoms as well as neuro-ophthalmologic abnormalities. "A secondary form of MNGIE, called MNGIE without leukoencephalopathy, can be caused by mutations in the POLG gene".

In common forms of MTHFR deficiency, elevated plasma homocysteine levels have sometimes been treated with Vitamin B12 and low doses of folic acid. Although this treatment significantly decreases the serum levels of homocysteine, this treatment is not thought to improve health outcomes.

Due to the ineffectiveness of these treatments, it is no-longer considered clinically useful to test for MTHFR in most cases of thrombophilia or recurrent pregnancy loss.

Infant mortality is high for patients diagnosed with early onset; mortality can occur within less than 2 months, while children diagnosed with late-onset syndrome seem to have higher rates of survival. Patients suffering from a complete lesion of mut0 have not only the poorest outcome of those suffering from methylaonyl-CoA mutase deficiency, but also of all individuals suffering from any form of methylmalonic acidemia.

Vitamin E supplements have shown to help children with the deficiency.

That MMA can have disastrous effects on the nervous system has been long reported; however, the mechanism by which this occurs has never been determined. Published on June 15th 2015, research performed on the effects of methylmalonic acid on neurons isolated from fetal rats in an in vitro setting using a control group of neurons treated with an alternate acid of similar pH. These tests have suggested that methylmalonic acid causes decreases in cellular size and increase in the rate of cellular apoptosis in a concentration dependent manner with more extreme effects being seen at higher concentrations. Furthermore, micro-array analysis of these treated neurons have also suggested that on a epigenetic-level methylmalonic acid alters the transcription rate of 564 genes, notably including those involved in the apoptosis, p53, and MAPK signaling pathways.

The prognosis will vary depending on the severity of the condition and the individual's response to treatment. Prognosis is typically better for those with cobalamin-responsive variants and not promising in those suffering from noncobalamin-responsive variants, typically the milder variants have a higher frequency of appearance in the population than the more severe ones. Even with dietary modification and continued medical care, it may not be possible to prevent neurological damage in those with a nonresponsive acidemia. Without proper treatment or diagnosis, it not uncommon for the first acidemic attack to be fatal.

Despite these challenges, since it was first identified in 1967, treatment and understanding of the condition has improved to the point where it is not unheard of for even those with unresponsive forms of methylmalonic acidemia to be able to reach adulthood and even carry and deliver children safely.

Treatment of LPLD has two different objectives: immediate prevention of pancreatitis attacks and long term reduction of cardiovascular disease risk. Treatment is mainly based on medical nutrition therapy to maintain plasma triglyceride concentration below 11,3 mmol/L (1000 mg/dL). Maintenance of triglyceride levels below 22,6 mmol/L (2000 mg/dL) prevents in general from recurrent abdominal pain.

Strict low fat diet and avoidance of simple carbohydrates

Restriction of dietary fat to not more than 20 g/day or 15% of the total energy intake is usually sufficient to reduce plasma triglyceride concentration, although many patients report that to be symptom free a limit of less than 10g/day is optimal. Simple carbohydrates should be avoided as well. Medium-chain triglycerides can be used for cooking, because they are absorbed into the portal vein without becoming incorporated into chylomicrons. Fat-soluble vitamins A, D, E, and K, and minerals should be supplemented in patients with recurrent pancreatitis since they often have deficiencies as a result of malabsorption of fat. However, the diet approach is difficult to sustain for many of the patients.

Lipid lowering drugs

Lipid-lowering agents such as fibrates and omega-3-fatty acids can be used to lower TG levels in LPLD, however those drugs are very often not effective enough to reach treatment goals in LPLD patients. Statins should be considered to lower elevated non-HDL-Cholesterol.

Additional measures are avoidance of agents known to increase endogenous triglyceride levels, such as alcohol, estrogens, diuretics, isotretinoin, anidepressants (e.g. sertraline) and b-adrenergic blocking agents.

Gene therapy

In 2012, the European Commission approved alipogene tiparvovec (Glybera), a gene therapy for adults diagnosed with familial LPLD (confirmed by genetic testing) and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. It was the first gene therapy to receive marketing authorization in Europe; it was priced at about $1 million per treatment, and as of 2016, only one person had been treated with it.

This is a rare disease with prevalence about 1 in 200,000 to 1 in 600,000. Studies showed that mutations in "CUBN" or "AMN" clustered particularly in the Scandinavian countries and the Eastern Mediterranean regions. Founder effect, higher clinical awareness to IGS, and

frequent consanguineous marriages all play a role in the higher prevalence of IGS among these populations