Mucolipidosis type IV is severely under-diagnosed. It is often misdiagnosed as cerebral palsy. In the Ashkenazi Jewish population there are two severe mutations with a higher carrier frequency of 1:90 to 1:100.

Mucolipidosis type IV (ML IV or ML4) is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation channel, mucolipin1. These mutations disrupt cellular functions and lead to a neurodevelopmental disorder through an unknown mechanism. Researchers dispute the physiological role of the protein product and which ion it transports.

I-cell disease is an autosomal recessive disorder caused by a deficiency of GlcNAc phosphotransferase, which phosphorylates mannose residues to mannose-6-phosphate on N-linked glycoproteins in the Golgi apparatus within the cell. Without mannose-6-phosphate to target them to the lysosomes, the enzymes are transported from the Golgi to the extracellular space, resulting in large intracellular inclusions of molecules requiring lysosomal degradation in patients with the disease (hence the name of the disorder). Hydrolases secreted into the blood stream cause little problem as they are deactivated in the neutral pH of the blood.

It can be associated with GNPTA.

In a case report, it was complicated by severe dilative cardiomyopathy(DCM)

Though rare, a deficiency of phosphodiesterase which would cleave GlcNAc from the Mannose 6 Phosphate tag will also cause I-Cell. The presence of lipids, glycosaminoglycans (GAG's) and carbohydrates in the blood provide for the distinguishing characteristic to separate I-Cell from Hurlers Syndrome, in Hurlers, only glycosaminoglycans would be present.

Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II (ML II), is part of the lysosomal storage disease family and results from a defective phosphotransferase (an enzyme of the Golgi apparatus). This enzyme transfers phosphate to mannose residues on specific proteins. Mannose 6 phosphate serves as a marker for them to be targeted to lysosomes within the cell. Without this marker, the proteins are instead excreted outside the cell—the default pathway for proteins moving through the Golgi apparatus. Lysosomes cannot function without these proteins, which function as catabolic enzymes for the normal breakdown of substances (e.g. oligosaccharides, lipids, and glycosaminoglycans) in various tissues throughout the body (i.e. fibroblasts). As a result, a buildup of these substances occurs within lysosomes because they cannot be degraded, resulting in the characteristic I-cells, or "inclusion cells". These cells can be identified under the microscope. In addition, the defective lysosomal enzymes normally found only within lysosomes are instead found in high concentrations in the blood.

Mucolipidosis type I (ML I) or sialidosis is an inherited lysosomal storage disease that results from a deficiency of the enzyme alpha-N -acetyl neuraminidase (sialidase). The lack of this enzyme results in an abnormal accumulation of complex carbohydrates known as mucopolysaccharides, and of fatty substances known as mucolipids. Both of these substances accumulate in bodily tissues.

Pseudo-Hurler polydystrophy, also referred to as mucolipidosis III (ML III), is a lysosomal storage disease closely related to I-cell disease (ML II). This disorder is called Pseudo-Hurler because it resembles a mild form of Hurler syndrome, one of the mucopolysaccharide (MPS) diseases.

Mucolipidosis (ML) is a group of inherited metabolic disorders that affect the body's ability to carry out the normal turnover of various materials within cells.

When originally named, the mucolipidoses derived their name from the similarity in presentation to both mucopolysaccharidoses and sphingolipidoses. A biochemical understanding of these conditions has changed how they are classified. Although four conditions (I, II, III, and IV) have been labeled as mucolipidoses, type I (sialidosis) is now classified as a glycoproteinosis, and type IV (Mucolipidosis type IV) is now classified as a gangliosidosis.

As in Mucolipidosis II, Mucolipidosis III results from genetic defects in GlcNAc phosphotransferase (N-acetylglucosamine-1-phosphotransferase). However, ML III produces less severe symptoms and progresses more slowly, probably because the defect in GlcNAc phosphotranspherase lies in its protein recognition domain. Therefore, the catalytic domain retains some of its activity, resulting in a smaller accumulation of carbohydrates, lipids, and proteins in the inclusion bodies.

The other two types are closely related.

Mucolipidosis types II and III (ML II and ML III) result from a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase, which phosphorylates target carbohydrate residues on N-linked glycoproteins. Without this phosphorylation, the glycoproteins are not destined for lysosomes, and they escape outside the cell.

Other diseases that result from a deficiency in the sialidase enzyme are categorized in a broader group known as sialidoses. Because ML I is classified as a sialidosis, it is sometimes referred to as sialidosis type II.

A rarer form of sialidosis – sialidosis type 1– occurs in children and adolescents and is often referred to as the juvenile form of the disorder. Children usually begin to show symptoms during the second decade of life, and myoclonus and cherry-red macules are often the initial symptoms. Patients usually develop seizures and progressive deterioration of coordinated muscular and mental activities.

Heterozygous protein C deficiency occurs in 0.14–0.50% of the general population. Based on an estimated carrier rate of 0.2%, a homozygous or compound heterozygous protein C deficiency incidence of 1 per 4 million births could be predicted, although far fewer living patients have been identified. This low prevalence of patients with severe genetic protein C deficiency may be explained by excessive fetal demise, early postnatal deaths before diagnosis, heterogeneity in the cause of low concentrations of protein C among healthy individuals and under-reporting.

The incidence of protein C deficiency in individuals who present with clinical symptoms has been reported to be estimated at 1 in 20,000.

Based on studies conducted in the United States, the prognosis for individuals with ALECT2 amyloidosis is guarded, particularly because they are elderly and their kidney disease is usually well-advanced at the time of presentation. End-stage renal disease develops in 1 out of 3 patients and has a median renal survival of 62 months. A suggested prognostic tool is to track creatinine levels in ALect2 patients. The attached Figure gives survival plotss for individuals with LECT2 renal amyloidosis and serum creatinine levels less than 2 mg/100 ml versus 2 mg/100 ml or greater than 2 mg/100 ml. The results show that afflicted individuals with lower creatinine levels have a ~four-fold higher survival rate.

The prognosis is guarded with an overall mortality of 50%. Poor prognostic factors included HLH associated with malignancy, with half the patients dying by 1.4 months compared to 22.8 months for non-tumour associated HLH patients.

Secondary HLH in some individuals may be self-limited because patients are able to fully recover after having received only supportive medical treatment (i.e., IV immunoglobulin only). However, long-term remission without the use of cytotoxic and immune-suppressive therapies is unlikely in the majority of adults with HLH and in those with involvement of the central nervous system (brain and/or spinal cord).

Protein C deficiency is a rare genetic trait that predisposes to thrombotic disease. It was first described in 1981. The disease belongs to a group of genetic disorders known as thrombophilias. Protein C deficiency is associated with an increased incidence of venous thromboembolism (relative risk 8–10), whereas no association with arterial thrombotic disease has been found.

Congenital dyserythropoietic anemia (CDA) is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells (RBCs) in the body and a less than normal quantity of hemoglobin in the blood.

LECT2 Amyloidosis is a form of amyloidosis caused by the LECT2 protein. It was found to be the third most common (~3% of total) cause of amyloidosis in a set of more than 4,000 individuals studied at the Mayo Clinic; the first and second most common forms the disorder were AL amyloidosis and AA amyloidosis, respectively. Amyloidosis is a disorder in which the abnormal deposition of a protein in organs and/or tissues gradually leads to organ failure and/or tissue injury.

Although more than 30 different proteins can cause amyloidosis, the disorder caused by LECT2 is distinctive in three ways. First, it has an unusually high incidence in certain ethnic populations. Second, it is a systemic form of amyloidosis (i.e. amyloid deposited in multiple organs), as opposed to a localized form (amyloid deposits limited to a single organ) but nonetheless injures the kidney without or rarely injuring the other organs in which it is deposited. Third, LECT2 amyloidosis is diagnosed almost exclusively in elderly individuals.

Given its relatively recent discovery, exceptionally strong ethnic bias, limitation to causing kidney disease, and restriction to elderly individuals, LECT2 amyloidosis appears at present to be an under-recognized cause of chronic kidney disease particularly in the ethnic groups that exhibit a high incidence of the disorer.

Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages, characterised by proliferation of morphologically benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes.

Autoimmune lymphoproliferative syndrome (ALPS), also known as Canale-Smith syndrome, is a form of lymphoproliferative disorder (LPDs). It affects lymphocyte apoptosis. It is a RASopathy.

It is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Normally, after infectious insult, the immune system down-regulates by increasing Fas expression on activated B and T lymphocytes and Fas-ligand on activated T lymphocytes. Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this apoptotic pathway, leading to chronic non-malignant lymphoproliferation, autoimmune disease, and secondary cancers.

It is most common in certain European populations (such as the Irish and Norwegians) and occurs in 0.6% of the population. Men with the disease are 24 times more likely to experience symptoms than affected women.

Affected individuals over age 40 or who have high serum ferritin levels are at risk for developing cirrhosis. Iron overload increases the risk of hepatocellular carcinoma. This risk is greater in those with cirrhosis but is still present in those without cirrhosis. Significant problems occur in around one in ten.

The incidence of the disease is higher in people from certain parts of the world including South-East Asia, South Africa and the Middle East.

Although the cause is unknown, genetic factors play a role in some cases, with a family history of multiple endocrine neoplasia type 1 (MEN 1) being a risk factor. These tumors are usually cancerous, with the cancer spreading and getting worse.

A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone glucagon. Alpha cell tumors are commonly associated with glucagonoma syndrome, though similar symptoms are present in cases of pseudoglucagonoma syndrome in the absence of a glucagon-secreting tumor.

This condition is usually caused by mutations in the FAS gene. Rarely cases due to mutations in other genes including the

FAS ligand gene have been reported.

To minimize the risk for contrast-induced nephropathy, various actions can be taken if the patient has predisposing conditions. These have been reviewed in a meta-analysis. A separate meta-analysis addresses interventions for emergency patients with baseline insufficient kidney function.

Individuals with chronic kidney disease, diabetes mellitus, high blood pressure, reduced intravascular volume, or who are elderly are at increased risk of developing CIN after exposure to iodinated contrast.

A clinical prediction rule is available to estimate probability of nephropathy (increase ≥25% and/or ≥0.5 mg/dl in serum creatinine at 48 h):

Risk Factors:

- Systolic blood pressure <80 mm Hg - 5 points

- Intraarterial balloon pump - 5 points

- Congestive heart failure (Class III-IV or history of pulmonary edema) - 5 points

- Age >75 y - 4 points

- Hematocrit level <39% for men and <35% for women - 3 points

- Diabetes mellitus- 3 points

- Contrast media volume - 1 point for each 100 mL

- Decreased kidney function:

- Serum creatinine level >1.5 g/dL - 4 points

- Estimated Glomerular filtration rate (online calculator)

Scoring:

5 or less points

- Risk of CIN - 7.5

- Risk of Dialysis - 0.04%

6–10 points

- Risk of CIN - 14.0

- Risk of Dialysis - 0.12%

11–16 points

- Risk of CIN - 26.1*

- Risk of Dialysis - 1.09%

>16 points

- Risk of CIN - 57.3

- Risk of Dialysis - 12.8%