Malonyl-CoA decarboxylase deficiency (MCD), or Malonic aciduria is an autosomal-recessive metabolic disorder caused by a genetic mutation that disrupts the activity of Malonyl-Coa decarboxylase. This enzyme breaks down Malonyl-CoA (a fatty acid precursor and a fatty acid oxidation blocker) into Acetyl-CoA and carbon dioxide.

The signs and symptoms of this disorder typically appear in early childhood. Almost all affected children have delayed development. Additional signs and symptoms can include weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low blood sugar (hypoglycemia). A heart condition called cardiomyopathy, which weakens and enlarges the heart muscle, is another common feature of malonyl-CoA decarboxylase deficiency.

Some common symptoms in Malonyl-CoA decarboxylase deficiency, such as cardiomyopathy and metabolic acidosis, are triggered by the high concentrations of Malonyl-CoA in the cytoplasm. High level of Malonyl-CoA will inhibits β-oxidation of fatty acids through deactivating the carrier of fatty acyl group, CPT1, and thus, blocking fatty acids from going into the mitochondrial matrix for oxidation.

A research conducted in Netherlands has suggested that carnitine supplements and a low fat diet may help to reduce the level of malonic acid in our body.

Microlissencephaly is listed in Orphanet database as a rare disease. There is no much information available about the epidemiology of microlissencepahly in literature. A PhD thesis has estimated the prevalence of microlissencepahly in South–Eastern Hungary between July 1992 and June 2006 to be a case every 91,000 live births (0.11:10,000).

Microlissencephaly (MLIS) is a rare congenital brain disorder that combines severe microcephaly (small head) with lissencephaly (smooth brain surface due to absent sulci and gyri). Microlissencephaly is a heterogeneous disorder i.e. it has many different causes and a variable clinical course. Microlissencephaly is a malformation of cortical development (MCD) that occurs due to failure of neuronal migration between the third and fifth month of gestation as well as stem cell population abnormalities. Numerous genes have been found to be associated with microlissencephaly, however, the pathophysiology is still not completely understood.

The combination of lissencephaly with severe congenital microcephaly is designated as microlissencephaly only when the cortex is abnormally thick. If such combination exists with a normal cortical thickness (2.5 to 3 mm), it is known as "microcephaly with simplified gyral pattern" (MSGP). Both MLIS and MSGP have a much more severe clinical course than microcephaly alone. They are inherited in autosomal recessive manner. Prior to 2000, the term “microlissencephaly” was used to designate both MLIS and MSGP.

Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome in children and adolescents, as well as a leading cause of kidney failure in adults. It is also known as "focal glomerular sclerosis" or "focal nodular glomerulosclerosis". It accounts for about a sixth of the cases of nephrotic syndrome. (Minimal change disease (MCD) is by far the most common cause of nephrotic syndrome in children: MCD and primary FSGS may have a similar cause.)

Macular corneal dystrophy, also known as Fehr corneal dystrophy named for German ophthalmologist Oskar Fehr (1871-1959), is a rare pathological condition affecting the stroma of cornea. The first signs are usually noticed in the first decade of life, and progress afterwards, with opacities developing in the cornea and attacks of pain. The condition was first described by Arthur Groenouw in 1890.

Corticosteroids such as prednisone are often prescribed along with a blood pressure medication, typically an ACE inhibitor such as lisinopril. Some nephrologists will start out with the ACE inhibitor first in an attempt to reduce the blood pressure's force which pushes the protein through the cell wall in order to lower the amount of protein in the urine. In some cases, a corticosteroid may not be necessary if the case of minimal change disease is mild enough to be treated just with the ACE inhibitor. Often, the liver is overactive with minimal change disease in an attempt to replace lost protein and overproduces cholesterol. Therefore, a statin drug is often prescribed for the duration of the treatment. When the urine is clear of protein, the medications can be discontinued. Fifty percent of patients will relapse and need further treatment with immunosuppressants, such as cyclosporine and tacrolimus.

Minimal change disease usually responds well to initial treatment and over 90% of patients will respond to oral steroids within 6–8 weeks, with most of these having a complete remission. Symptoms of nephrotic syndrome (NS) typically go away; but, this can take from 2 weeks to many months. Younger children, who are more likely to develop minimal change disease, usually respond faster than adults. In 2 out of 3 children with minimal change disease; however, the symptoms of NS can recur, called a relapse, particularly after an infection or an allergic reaction. This is typical and usually requires additional treatment. Many children experience 3 to 4 relapses before the disease starts to go away. Some children require longer term therapy to keep MCD under control. It appears that the more time one goes without a relapse, the better the chances are that a relapse will not occur. In most children with minimal change disease, particularly among those who respond typically, there is minimal to no permanent damage observed in their kidneys.

With corticosteroid treatment, most cases of nephrotic syndrome from minimal change disease in children will go into remission. This typically occurs faster, over 2 to 8 weeks, in younger children, but can take up to 3 or 4 months in adults. Typically, the dose of corticosteroids will initially be fairly high, lasting 1or 2 months. When urine protein levels have normalised, corticosteroids are gradually withdrawn over several weeks (to avoid triggering an Addisonian crisis). Giving corticosteroids initially for a longer period of time is thought to reduce the likelihood of relapse. The majority of children with minimal change disease will respond to this treatment.

Even among those who respond well to corticosteroids initially, it is common to observe periods of relapse (return of nephrotic syndrome symptoms). 80% of those who get minimal change disease have a recurrence. Because of the potential for relapse, the physician may prescribe and teach the patient how to use a tool to have them check urine protein levels at home. Two out of 3 children who initially responded to steroids will experience this at least once. Typically the steroids will be restarted when this occurs, although the total duration of steroid treatment is usually shorter during relapses than it is during the initial treatment of the disease.

There are several immunosuppressive medications that can be added to steroids when the effect is insufficient or can replace them if intolerance or specific contraindications are encountered.

Macular corneal dystrophy is inherited in autosomal recessive fashion and is thought to be caused by the lack or abnormal configuration of keratan sulfate. Most cases of MCD are caused by mutations in CHST6 gene.

The gene CHST6 is a carbohydrate sulfotransferase encoding an enzyme designated corneal N-acetylglucosamine-6-sulfotransferase. In MCD type I, various mutations lead to inactivation of the enzyme, in MCD type II, inactivation is caused by large deletions and/or replacements in the gene.

The individual components of the name refer to the appearance of the kidney tissue on biopsy: "focal"—only some of the glomeruli are involved (as opposed to diffuse), "segmental"—only part of each glomerulus is involved (as opposed to global), "glomerulosclerosis"—refers to scarring of the glomerulus (a part of the nephron (the functional unit of the kidney)). The glomerulosclerosis is usually indicated by heavy PAS staining and findings of immunoglobulin M (IgM) and C3-convertase (C3) in the sclerotic segment.

Minimal change disease is most common in very young children but can occur in older children and adults. It is by far the most common cause of nephrotic syndrome in children between the ages of 1 and 7, accounting for the majority (about 90%) of these diagnoses. Among teenagers who develop nephrotic syndrome, it is caused by minimal change disease about half the time. It can also occur in adults but accounts for less than 20% of adults diagnosed with nephrotic syndrome. Among children less than 10 years of age, boys seem to be more likely to develop minimal change disease than girls. Minimal change disease is being seen with increasing frequency in adults over the age of 80.

People with one or more autoimmune disorders are at increased risk of developing minimal change disease. Having minimal change disease also increases the chances of developing other autoimmune disorders.

The treatment of nephrotic syndrome can be symptomatic or can directly address the injuries caused to the kidney.

The objective of this treatment is to treat the imbalances brought about by the illness: edema, hypoalbuminemia, hyperlipemia, hypercoagulability and infectious complications.

- Edema: a return to an unswollen state is the prime objective of this treatment of nephrotic syndrome. It is carried out through the combination of a number of recommendations:

- Rest: depending on the seriousness of the edema and taking into account the risk of thrombosis caused by prolonged bed rest.

- Medical nutrition therapy: based on a diet with the correct energy intake and balance of proteins that will be used in synthesis processes and not as a source of calories. A total of 35 kcal/kg body weight/day is normally recommended. This diet should also comply with two more requirements: the first is to not consume more than 1 g of protein/kg body weight/ day, as a greater amount could increase the degree of proteinuria and cause a negative nitrogen balance. Patients are usually recommended lean cuts of meat, fish, and poultry. The second guideline requires that the amount of water ingested is not greater than the level of diuresis. In order to facilitate this the consumption of salt must also be controlled, as this contributes to water retention. It is advisable to restrict the ingestion of sodium to 1 or 2 g/day, which means that salt cannot be used in cooking and salty foods should also be avoided. Foods high in sodium include seasoning blends (garlic salt, Adobo, season salt, etc.) canned soups, canned vegetables containing salt, luncheon meats including turkey, ham, bologna, and salami, prepared foods, fast foods, soy sauce, ketchup, and salad dressings. On food labels, compare milligrams of sodium to calories per serving. Sodium should be less than or equal to calories per serving.

- Medication: The pharmacological treatment of edema is based on the prescription of diuretic drugs (especially loop diuretics, such as furosemide). In severe cases of edema (or in cases with physiological repercussions, such as scrotal, preputial or urethral edema) or in patients with one of a number of severe infections (such as sepsis or pleural effusion), the diuretics can be administered intravenously. This occurs where the risk from plasmatic expansion is considered greater than the risk of severe hypovolemia, which can be caused by the strong diuretic action of intravenous treatment. The procedure is the following:

- Hypoalbuminemia: is treated using the medical nutrition therapy described as a treatment for edema. It includes a moderate intake of foods rich in animal proteins.

- Hyperlipidaemia: depending of the seriousness of the condition it can be treated with medical nutrition therapy as the only treatment or combined with drug therapy. The ingestion of cholesterol should be less than 300 mg/day, which will require a switch to foods that are low in saturated fats. Avoid saturated fats such as butter, cheese, fried foods, fatty cuts of red meat, egg yolks, and poultry skin. Increase unsaturated fat intake, including olive oil, canola oil, peanut butter, avocadoes, fish and nuts. In cases of severe hyperlipidaemia that are unresponsive to nutrition therapy the use of hypolipidemic drugs, may be necessary (these include statins, fibrates and resinous sequesters of bile acids).

- Thrombophilia: low molecular weight heparin (LMWH) may be appropriate for use as a prophylactic in some circumstances, such as in asymptomatic patients that have no history of suffering from thromboembolism. When the thrombophilia is such that it leads to the formation of blood clots, heparin is given for at least 5 days along with oral anticoagulants (OAC). During this time and if the prothrombin time is within its therapeutic range (between 2 and 3), it may be possible to suspend the LMWH while maintaining the OACs for at least 6 months.

- Infectious complications: an appropriate course of antibacterial drugs can be taken according to the infectious agent.

In addition to these key imbalances, vitamin D and calcium are also taken orally in case the alteration of vitamin D causes a severe hypocalcaemia, this treatment has the goal of restoring physiological levels of calcium in the patient.

- Achieving better blood glucose level control if the patient is diabetic.

- Blood pressure control. ACE inhibitors are the drug of choice. Independent of their blood pressure lowering effect, they have been shown to decrease protein loss.

A new model of pathogenesis (lymph node changes are not “benign tumors” that secrete cytokines, but reactive changes due to excessive cytokine release from an as-yet unknown cause) and a new classification system for MCD (based on HHV-8 status) have ensued. CDCN has launched a platform for online discussion among physicians and researchers, developed a global research agenda, and launched a global patient community in partnership with EURODIS and NORD. Current strategic priorities include: 1) establishing a global patient registry, 2) empowering the global patient community to support one another and join the fight against CD, and 3) distributing high-impact research grants.

There is no standard therapy for multicentric Castleman disease. Treatment modalities change based on HHV-8 status, so it is essential to determine HHV-8 status before beginning treatment. For HHV-8-associated MCD the following treatments have been used: rituximab, antiviral medications such as ganciclovir, and chemotherapy.

Treatment with the antiherpesvirus medication ganciclovir or the anti-CD20 B cell monoclonal antibody, rituximab, may markedly improve outcomes. These medications target and kill B cells via the B cell specific CD20 marker. Since B cells are required for the production of antibodies, the body's immune response is weakened whilst on treatment and the risk of further viral or bacterial infection is increased. Due to the uncommon nature of the condition there are not many large scale research studies from which standardized approaches to therapy may be drawn, and the extant case studies of individuals or small cohorts should be read with caution. As with many diseases, the patient's age, physical state and previous medical history with respect to infections may impact the disease progression and outcome.

Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is sometimes called the plasmablastic form of multicentric Castleman disease. It has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. It has variable CD20 expression and unmutated immunoglobulin variable region genes.

Castleman disease (CD) is a lymphoproliferative disorder of unknown cause. CD is associated with an increased risk of B-cell lymphoma.

Human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV) has been found in some cases of multicentric Castleman disease (MCD). The HHV8 can give rise to an increased number of plasmablast cells within the mantle zone of B-cell follicles. These plasmablasts express IgM-immunoglobulin light chains, most often of lambda subtype. These plasmablasts can give rise to a spectrum of abnormalities including progression to microlymphoma (microscopic clusters of plasmablast cells) or clinical lymphoma.

This type of lymphoma is predominantly seen in acquired immunodeficiencies, including acquired immunodeficiency syndrome (AIDS) but it can also occur in immunosuppression such as with organ transplantation or the elderly. The plasmablasts do not show rearranged immunoglobulin genes, and typically lack EBV infection.

The disease predominantly affects lymph nodes and the spleen, a pattern dissimilar to plasmablastic lymphoma of the oral cavity of AIDS which is not associated with HHV-8 infection. Despite traditional chemotherapy with CHOP (cyclophosphamide, doxorubicin, prednisone, vincristine), and the possible addition of antiviral therapy and inhibition of specific cellular targets including the use of rituximab, the prognosis in this lymphoma has been poor.

This lymphoma subtype has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. Similarly, this subtype is considered distinct from other lymphomas which have a plasmablastic immunophenotype such as primary effusion lymphoma, ALK+ large B-cell lymphoma, and extracavitary HHV–8-positive lymphoma.

HHV8 is also associated with Kaposi's sarcoma and with another subtype of lymphoma, primary effusion lymphoma, previously called body cavity-based lymphoma.