In terms of the treatment for ativated PI3K delta syndrome, generally primary immunodeficiencies see the following used:

- Bacterial infection should be treated rapidly(with antibiotics)

- Antiviral therapy

- Modify lifestyle(exposure to pathogens need to be minimized)

Canakinumab has been approved for treatment of HIDS and has shown to be effective. The immunosuppressant drugs etanercept and anakinra have also shown to be effective. Statin drugs might decrease the level of mevalonate and are presently being investigated. A recent single case report highlighted bisphosphonates as a potential therapeutic option.

There is no treatment for MKD. But, the inflammation and the other effects can be reduced to a certain extent.

- IL-1 targeting drugs can be used to reduce the effects of the disorder. Anakinra is antagonist to IL-1 receptors. Anakinra binds the IL-1 receptor, preventing the actions of both IL-1α and IL-1β, and it has been proved to reduce the clinical and biochemical inflammation in MKD. It can effectively decreases the frequency as well as the severity of inflammatory attacks when used on a daily basis. Disadvantages with the usage of this drug are occurrence of painful injection site reaction and as the drug is discontinued in the near future the febrile attacks start. (Examined in a 12-year-old patient).

- Canakinumab is a long acting monoclonal antibody which is directed against IL-1β has shown to be effective in reducing both frequency and severity in patients suffering from mild and severe MKD in case reports and observational case series. It reduces the physiological effects but the biochemical parameter still remain elevated (Galeotti et al. demonstrated that it is more effective than anakinra –considered 6 patients suffering from MKD).

- Anti-TNF therapy might be effective in MKD, but the effect is mostly partial and therapy failure and clinical deterioration have been described frequently in patients on infliximab or etanercept. A beneficial effect of human monoclonal anti-TNFα antibody adalimumab was seen in a small number of MKD patients.

- Most MKD patients are benefited by anti-IL-1 therapy. However, anti-IL-1-resistant disease may also occur. Example. tocilizumab (a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor). This drug is used when the patients are unresponsive towards Anakinra. (Shendi et al. treated a young woman in whom anakinra was ineffective with tocilizumab). It was found that it was effective in reducing the biochemical and clinical inflammation [30].Stoffels et al. observed reduction of frequency and severity of the inflammatory attacks, although after several months of treatment one of these two patients persistently showed mild inflammatory symptoms in the absence of biochemical inflammatory markers.

- A beneficial effect of hematopoietic stem cell transplantation can be used in severe mevalonate kinase deficiency conditions (Improvement of cerebral myelinisation on MRI after allogenic stem cell transplantation was observed in one girl). But, liver transplantation did not influence febrile attacks in this patient.

Activated PI3K delta syndrome is a primary immunodeficiency disease caused by activating gain of function mutations in the PIK3CD gene. Which encodes the p110δ catalytic subunit of PI3Kδ, APDS-2 (PASLI-R1) is caused by exon-skipping mutations in PIK3R1 which encodes for the regulatory subunit p85α. APDS and APDS-2 affected individuals present with similar symptoms, which include increased susceptibility to airway infections, bronchiectasis and lymphoproliferation.

Once a diagnosis is made, the treatment is based on an individual’s clinical condition. Based on the apparent activation of the mTOR pathway, Lucas and colleagues treated patients with rapamycin, an mTOR inhibitor. This effectively reduced hepatosplenomegaly and lymphadenopathy, most likely by restoring the normal balance of naïve, effector, and memory cells in the patients’ immune system. More research is needed to determine the most effective timing and dosage of this medication and to investigate other treatment options. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

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 no cure and no standard course of treatment for Coffin–Lowry syndrome. Treatment is symptomatic and supportive, and may include occupational, physical and speech therapy and educational services.

There is no cure for McLeod syndrome; the treatment is supportive depending on symptoms. Medication may assist with management of epilepsy, and cardiac and psychiatric features, although patients may respond poorly to treatment for chorea.

During prolonged periods of fasting, ketone bodies serve as the primary energy source for the brain. In 2006, Henderson et al. showed that there is a therapeutic effect of maintaining a ketogenic diet – a diet consisting of high fat/low carbohydrate meals – in children with epilepsy. Ketogenic diets have also been shown to have some neuroprotective effects in models of Parkinson's disease and hypoxia as well. In a recent study conducted at the Hospital for Sick Children in Canada in 2007, researchers found that a ketogenic diet prolonged the lifespan of Aldh5a1-/- mice by greater than 300%, along with the normalization of ataxia and some improvement in various seizure types seen in SSADH deficient murine models. These effects were in conjunction with "...a significant restoration of GABAergic synaptic activity and region-specific restoration of GABA receptor associated chloride channel binding." Ultimately, the data seen in the study indicated that a ketogenic diet may work in its ability to restore GABAergic inhibition. But further studies on murine models need to be conducted, ultimately leading to the possibility of conducting a controlled study on humans afflicted with the disorder.

There is speculation that a ketogenic diet may be harmful for humans with SSADH deficiency as it may cause elevated levels of GHB in the bloodstream.

While SSADH deficiency has been studied for nearly 30 years, knowledge of the disorder and its pathophysiology remains unclear. However, the progress that has been made with both murine and human models of the disorder have provided a lot of insights into how the disease manifests itself and what more can be done in terms of therapeutic interventions. Much of the current research into SSADH has been led by a dedicated team of physicians and scientists, including Phillip L. Pearl, MD of the Boston Children's Hospital at Harvard Medical School and K. Michael Gibson, PhD of Washington State University College of Pharmacy. Both have contributed significant efforts to finding appropriate therapies for SSADH deficiency and have specifically spent most of their recent efforts into understanding the efficacy of the ketogenic diet for patients with SSADH deficiency. In addition, a lot of the research that was published in 2007 examined the pathogenesis for the disorder by examining the role of oxidative stress on tissues in various cerebral structures of Aldh5a1-/- mice.

Ultimately, the metabolic pathway of SSADH deficiency is known, but how the enzyme deficiency and accumulation of GABA and GHB contribute to the clinical phenotype is not. For the future however, treatment strategies should focus on both decreasing the total production of GHB and increasing the total concentration of GABA and further assessing whether the effects of these changes influences the neurological manifestations seen in patients afflicted with SSADH deficiency.

Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

McLeod syndrome is present in 0.5 to 1 per 100,000 of the population. McLeod males have variable acanthocytosis due to a defect in the inner leaflet bilayer of the red blood cell, as well as mild hemolysis. McLeod females have only occasional acanthocytes and very mild hemolysis; the lesser severity is thought to be due to X chromosome inactivation via the Lyon effect. Some individuals with McLeod phenotype develop myopathy, neuropathy, or psychiatric symptoms, producing a syndrome that may mimic chorea.

McLeod syndrome can cause an increase in the enzymes creatine kinase (CK) and lactate dehydrogenase (LDH) found in routine blood screening.

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.

Life expectancy for individuals with hypochondroplasia is normal; the maximum height is about 147 cm or 4.8 ft.

In the world less than 1 in 1.00.000 have HIDS [5]. 200 individuals throughout the world do suffer from MVK.

The main treatment for acral erythema is discontinuation of the offending drug, and symptomatic treatment to provide analgesia, lessen edema, and prevent superinfection. However, the treatment for the underlying cancer of the patient must not be neglected. Often, the discontinued drug can be substituted with another cancer drug or cancer treatment.

Symptomatic treatment can include wound care, elevation, and pain medication. Corticosteroids and pyridoxine have also been used to relieve symptoms. Other studies do not support the conclusion.

A number of additional remedies are listed in recent medical literature. Among them henna and 10% uridine ointment which went through clinical trial.

PPE invariably recurs with the resumption of chemotherapy. Long-term chemotherapy may also result in reversible palmoplantar keratoderma. Symptoms resolve 1–2 weeks after cessation of chemotherapy (Apisarnthanarax and Duvic 2003).

Survival rates for those diagnosed with typical PKAN is 11.18 years with a standard deviation of 7.8 years.

PASLI disease is a rare genetic disorder of the immune system. PASLI stands for “p110 delta activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency.” The immunodeficiency manifests as recurrent infections usually starting in childhood. These include bacterial infections of the respiratory system and chronic viremia due to Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV). Individuals with PASLI disease also have an increased risk of EBV-associated lymphoma. Investigators Carrie Lucas, Michael Lenardo, and Gulbu Uzel at the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health and Sergey Nejentsev at the University of Cambridge, UK simultaneously described a mutation causing this condition which they called Activated PI3K Delta Syndrome (APDS).

Dolichol kinase deficiency is a cutaneous condition caused by a mutation in the dolichol kinase gene.

It is also known as Congenital disorder of glycosylation 1m.

It is not known how mevalonate kinase mutations cause the febrile episodes, although it is presumed that other products of the cholesterol biosynthesis pathyway, the prenylation chains (geranylgeraniol and farnesol) might play a role.

Raine syndrome (RNS), also called osteosclerotic bone dysplasia, is a rare autosomal recessive congenital disorder characterized by craniofacial anomalies including microcephaly, noticeably low set ears, osteosclerosis, a cleft palate, gum hyperplasia, a hypoplastic nose, and eye proptosis. It is considered to be a lethal disease, and usually leads to death within a few hours of birth. However, a recent report describes two studies in which children with Raine Syndrome have lived to 8 and 11 years old, so it is currently proposed that there is a milder expression that the phenotype can take (Simpson 2009).

It was first characterized in 1989 in a report that was published on an infant that had been born with an unknown syndrome, that later came to be called Raine Syndrome.

The current research describes Raine Syndrome as a neonatal osteosclerotic bone dysplasia, indicated by its osteosclerotic symptoms that are seen in those suffering from the disease. It has been found that a mutation in the gene FAM20C is the cause of the Raine Syndrome phenotype. This microdeletion mutation leads to an unusual chromosome 7 arrangement. The milder phenotypes of Raine Syndrome, such as those described in Simpson’s 2007 report, suggest that Raine Syndrome resulting from missense mutations may not be as lethal as the other described mutations (OMIM). This is supported by findings from Fradin et al. (2011), who reported on children with missense mutations to FAM20C and lived to ages 1 and 4 years, relatively much longer than the life spans of the previously reported children. Simpson et al.’s (2007) report states that to date, effected individuals have had chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion. They had abnormal chromosome 7 arrangements, with microdeletions of their D7S2477 and D7S1484 markers (Simpson 2007).

Raine Syndrome appears to be an autosomal recessive disease. There are reports of recurrence in children born of the same parents, and an increased occurrence in children of closely related, genetically similar parents. Individuals with Raine Syndrome were either homozygous or compound heterozygous for the mutation of FAM20C. Also observed have been nonsynonomous mutation and splice-site changes (Simpson et al. 2007).

FAM20C, located on chromosome 7p22.3, is an important molecule in bone development. Studies in mice have demonstrated its importance in the mineralization of bones in teeth in early development (OMIM, Simpson et al. 2007, Wang et al. 2010). FAM20C stands for “family with sequence similarity 20, member C.” It is also commonly referred to as DMP-4. It is a Golgi-enriched fraction casein kinase and an extracellular serine/threonine protein kinase. It is 107,743 bases long, with 10 exons and 584 amino acids (Weizmann Institute of Science).

CGL patients have to maintain a strict diet for life, as their excess appetite will cause them to overeat. Carbohydrate intake should be restricted in these patients. To avoid chylomicronemia, CGL patients with hypertriglyceridemia need to have a diet very low in fat. CGL patients also need to avoid total proteins, trans fats, and eat high amounts of soluble fiber to avoid getting high levels of cholesterol in the blood.

Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH), also known as Mental retardation, X-linked, syndromic, Najm type (MRXSNA), is a rare genetic disorder of infants characterised by intellectual disability and pontocerebellar hypoplasia.

The disorder is associated with a mutation in the "CASK" gene which is transmitted in an X-linked manner. As with the vast majority of genetic disorders, there is no known cure to MICPCH.

The following values seem to be aberrant in children with CASK gene defects: lactate, pyruvate, 2-ketoglutarate, adipic acid and suberic acid, which seems to backup the proposal that CASK affects mitochondrial function. It is also speculated that phosphoinositide 3-kinase in the inositol metabolism is impacted in the disease, causing folic acid metabolization problems.

In adults, fibrates and statins have been prescribed to treat hyperglycerolemia by lowering blood glycerol levels. Fibrates are a class of drugs that are known as amphipathic carboxylic acids that are often used in combination with Statins. Fibrates work by lowering blood triglyceride concentrations. When combined with statins, the combination will lower LDL cholesterol, lower blood triglycerides and increase HDL cholesterol levels.

If hyperglycerolemia is found in a young child without any family history of this condition, then it may be difficult to know whether the young child has the symptomatic or benign form of the disorder. Common treatments include: a low-fat diet, IV glucose if necessary, monitor for insulin resistance and diabetes, evaluate for Duchenne muscular dystrophy, adrenal insufficiency & developmental delay.

The Genetic and Rare Diseases Information Center (GARD) does not list any treatments at this time.

Janus kinase 3 deficiency or JAK3 deficiency is a defect in the body's cytokine receptors and their signaling. JAK3 encodes Janus kinase 3, a tyrosine kinase that belongs to the Janus family. JAK3 functions in signal transduction and interacts with members of the STAT (signal transduction and activators of transcription) family. The cause of JAK3 deficiency. The deficiency causes the near absence of T lymphocytes and Natural killer cells; and normal or elevated B lymphocytes due to an autosomal recessive variant of severe combined immunodeficiency (SCID).