The following characteristics suggest the possibility of a diagnosis of MODY in hyperglycemic and diabetic patients:

- Mild to moderate hyperglycemia (typically 130–250 mg/dl, or 7–14 mmol/l) discovered before 30 years of age. However, anyone under 50 can develop MODY.

- A first-degree relative with a similar degree of diabetes.

- Absence of positive antibodies or other autoimmunity (e.g., thyroiditis) in patient and family. However, Urbanova et al. found that about one quarter of Central European MODY patients are positive for islet cell autoantibodies (GADA and IA2A). Their expression is transient but highly prevalent. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. The islet cell autoantibodies are absent in MODY in at least some populations (Japanese, Britons).

- Persistence of a low insulin requirement (e.g., less than 0.5 u/kg/day) past the usual "honeymoon" period.

- Absence of obesity (although overweight or obese people can get MODY) or other problems associated with type 2 diabetes or metabolic syndrome (e.g., hypertension, hyperlipidemia, polycystic ovary syndrome).

- Insulin resistance very rarely happens.

- Cystic kidney disease in patient or close relatives.

- Non-transient neonatal diabetes, or apparent type 1 diabetes with onset before six months of age.

- Liver adenoma or hepatocellular carcinoma in MODY type 3

- Renal cysts, rudimentary or bicornuate uterus, vaginal aplasia, absence of the vas deferens, epidymal cysts in MODY type 5

The diagnosis of MODY is confirmed by specific gene testing available through commercial laboratories.

Currently, MODY is the final diagnosis in 1%–2% of people initially diagnosed with diabetes. The prevalence is 70–110 per million population. 50% of first-degree relatives will inherit the same mutation, giving them a greater than 95% lifetime risk of developing MODY themselves. For this reason, correct diagnosis of this condition is important. Typically patients present with a strong family history of diabetes (any type) and the onset of symptoms is in the second to fifth decade.

There are two general types of clinical presentation.

- Some forms of MODY produce significant hyperglycemia and the typical signs and symptoms of diabetes: increased thirst and urination (polydipsia and polyuria).

- In contrast, many people with MODY have no signs or symptoms and are diagnosed either by accident, when a high glucose is discovered during testing for other reasons, or screening of relatives of a person discovered to have diabetes. Discovery of mild hyperglycemia during a routine glucose tolerance test for pregnancy is particularly characteristic.

MODY cases may make up as many as 5% of presumed type 1 and type 2 diabetes cases in a large clinic population. While the goals of diabetes management are the same no matter what type, there are two primary advantages of confirming a diagnosis of MODY.

- Insulin may not be necessary and it may be possible to switch a person from insulin injections to oral agents without loss of glycemic control.

- It may prompt screening of relatives and so help identify other cases in family members.

As it occurs infrequently, many cases of MODY are initially assumed to be more common forms of diabetes: type 1 if the patient is young and not overweight, type 2 if the patient is overweight, or gestational diabetes if the patient is pregnant. Standard diabetes treatments (insulin for type 1 and gestational diabetes, and oral hypoglycemic agents for type 2) are often initiated before the doctor suspects a more unusual form of diabetes.

The classic symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss. Other symptoms that are commonly present at diagnosis include a history of blurred vision, itchiness, peripheral neuropathy, recurrent vaginal infections, and fatigue. Many people, however, have no symptoms during the first few years and are diagnosed on routine testing. A small number of people with type 2 diabetes mellitus can develop a hyperosmolar hyperglycemic state (a condition of very high blood sugar associated with a decreased level of consciousness and low blood pressure).

MODY 3 is a form of maturity onset diabetes of the young.

MODY 3 (also known as HNF1A-MODY) is caused by mutations of the HNF1-alpha; gene, a homeobox gene on chromosome 12. This is the most common type of MODY in populations with European ancestry, accounting for about 70% of all cases in Europe. HNF1α is a transcription factor (also known as transcription factor 1, TCF1) that is thought to control a regulatory network (including, among other genes, HNF1α) important for differentiation of beta cells. Mutations of this gene lead to reduced beta cell mass or impaired function. MODY 1 and MODY 3 diabetes are clinically similar. About 70% of people develop this type of diabetes by age 25 years, but it occurs at much later ages in a few. This type of diabetes can often be treated with sulfonylureas with excellent results for decades. However, the loss of insulin secretory capacity is slowly progressive and most eventually need insulin.

This is the form of MODY which can most resemble ordinary type 1 diabetes, and one of the incentives for diagnosing it is that insulin may be discontinued or deferred in favor of oral sulfonylureas. Some people treated with insulin for years due to a presumption of type 1 diabetes have been able to switch to pills and discontinue injections. Long-term diabetic complications can occur if the glucose is not adequately controlled.

High-sensitivity measurements of CRP may help to distinguish between HNF1A-MODY and other forms of diabetes

MODY 1 is a form of maturity onset diabetes of the young.

MODY 1 is due to a loss-of-function mutation in the gene on chromosome 20. This gene codes for HNF4-α protein also known as transcription factor 14 (TCF14). HNF4α controls function of HNF1α (see MODY 3; ) and perhaps HNF1β (MODY 5) as well. This transcription network plays a role in the early development of the pancreas, liver, and intestines. In the pancreas these genes influence expression of, among others, the genes for insulin, the principal glucose transporter (GLUT2), and several proteins involved in glucose and mitochondrial metabolism.

Although pancreatic beta cells produce adequate insulin in infancy, the capacity for insulin production declines thereafter. Diabetes (persistent hyperglycemia) typically develops by early adult years, but may not appear until later decades. The degree of insulin deficiency is slowly progressive. Many patients with MODY 1 are treated with sulfonylureas for years before insulin is required.

Liver effects are subtle and not clinically significant. Many people with this condition have low levels of triglycerides, lipoprotein(a), apolipoproteins AII and CIII.

Mutations in the alternative promoter of HNF4A are linked to development of type 2 diabetes.

Type 2 diabetes is typically a chronic disease associated with a ten-year-shorter life expectancy. This is partly due to a number of complications with which it is associated, including: two to four times the risk of cardiovascular disease, including ischemic heart disease and stroke; a 20-fold increase in lower limb amputations, and increased rates of hospitalizations. In the developed world, and increasingly elsewhere, type 2 diabetes is the largest cause of nontraumatic blindness and kidney failure. It has also been associated with an increased risk of cognitive dysfunction and dementia through disease processes such as Alzheimer's disease and vascular dementia. Other complications include acanthosis nigricans, sexual dysfunction, and frequent infections.

Low blood sugar is common in persons with type 1 and type 2 DM. Most cases are mild and are not considered medical emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild cases to more serious issues such as confusion, changes in behavior such as aggressiveness, seizures, unconsciousness, and (rarely) permanent brain damage or death in severe cases. Moderate hypoglycemia may easily be mistaken for drunkenness; rapid breathing and sweating, cold, pale skin are characteristic of hypoglycemia but not definitive. Mild to moderate cases are self-treated by eating or drinking something high in sugar. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.

People (usually with type 1 DM) may also experience episodes of diabetic ketoacidosis, a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness.

A rare but equally severe possibility is hyperosmolar hyperglycemic state, which is more common in type 2 DM and is mainly the result of dehydration.

The classic symptoms of untreated diabetes are weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger). Symptoms may develop rapidly (weeks or months) in type 1 DM, while they usually develop much more slowly and may be subtle or absent in type 2 DM.

Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known ones above, they include blurry vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.

MODY 2 is a form of maturity onset diabetes of the young.

MODY 2 is due to any of several mutations in the "GCK" gene on chromosome 7 for glucokinase. Glucokinase serves as the glucose sensor for the pancreatic beta cell. Normal glucokinase triggers insulin secretion as the glucose exceeds about 90 mg/dl (5 mM). These loss-of-function mutations result in a glucokinase molecule that is less sensitive or less responsive to rising levels of glucose. The beta cells in MODY 2 have a normal ability to make and secrete insulin, but do so only above an abnormally high threshold (e.g., 126–144 mg/dl, or 7-8 mM). This produces a chronic, mild increase in blood sugar, which is usually asymptomatic. It is usually detected by accidental discovery of mildly elevated blood sugar (e.g., during pregnancy screening). An oral glucose tolerance test is much less abnormal than would be expected from the impaired (elevated) fasting blood sugar, since insulin secretion is usually normal once the glucose has exceeded the threshold for that specific variant of the glucokinase enzyme.

The degree of blood sugar elevation does not worsen rapidly with age, and long-term diabetic complications are rare. In healthy children and adults, a high blood sugar level can be avoided by a healthy diet and exercise, primarily avoiding large amounts of carbohydrates. However, as people who have MODY2 enter their 50's and 60's, even though they continue to eat a healthy diet and exercise, they sometimes are unable to control a high blood sugar level with these measures. In these cases, many medicines for type II diabetes mellitus are not effective, because MODY2 does not cause insulin resistance. Repaglinide (Prandin) can help the body regulate the amount of glucose in the blood by stimulating the pancreas to release insulin before meals. In some cases, the baseline glucose levels are too high as well and insulin is required.

MODY2 is an autosomal dominant condition. Autosomal dominance refers to a single, abnormal gene on one of the first 22 nonsex chromosomes from either parent which can cause an autosomal disorder. Dominant inheritance means an abnormal gene from one parent is capable of causing disease, even though the matching gene from the other parent is normal. The abnormal gene "dominates" the pair of genes. If just one parent has a dominant gene defect, each child has a 50% chance of inheriting the disorder.

This type of MODY demonstrates the common circulation but complex interplay between maternal and fetal metabolism and hormone signals in the determination of fetal size. A small number of infants will have a new mutation not present in their mothers. If the mother is affected and the fetus is not, the maternal glucose will be somewhat high and the normal pancreas of the fetus will generate more insulin to compensate, resulting in a large infant. If the fetus is affected but mother is not, glucoses will be normal and fetal insulin production will be low, resulting in intrauterine growth retardation. Finally, if both mother and fetus have the disease, the two defects will offset each other and fetal size will be unaffected.

When both "GCK" genes are affected the diabetes appears earlier and the hyperglycemia is more severe. A form of permanent neonatal diabetes has been caused by homozygous mutations in the GCK gene.

MODY 4 is a form of maturity onset diabetes of the young.

MODY 4 arises from mutations of the PDX1 homeobox gene on chromosome 13. Pdx-1 is a transcription factor vital to the development of the embryonic pancreas. Even in adults it continues to play a role in the regulation and expression of genes for insulin, GLUT2, glucokinase, and somatostatin.

MODY 4 is so rare that only a single family has been well-studied. A child born with pancreatic agenesis (absence of the pancreas) was found to be homozygous for Pdx-1 mutations. A number of older relatives who were heterozygous had mild hyperglycemia or diabetes. None were severely insulin-deficient and all were controlled with either diet or oral hypoglycemic agents.

MODY 6 is a form of maturity onset diabetes of the young.

MODY 6 arises from mutations of the gene for the transcription factor referred to as neurogenic differentiation 1. The gene is on chromosome 2 in a region of the p arm known as IDDM7 because it includes genes affecting susceptibility to type 1 diabetes. NeuroD1 promotes transcription of the insulin gene as well as some genes involved in formation of beta cells and parts of the nervous system.

This is also one of the rarer forms of MODY. Only 3 kindreds with mutations causing MODY6 have been identified so far. In both, some of the members had more typical type 2 diabetes rather than MODY, and the reasons for the difference of expression have not been worked out. Most of the family members with diabetes were diagnosed after age 40, but a few required insulin for blood sugar control.

Renal cysts and diabetes syndrome (RCAD), also known as MODY 5, is a form of maturity onset diabetes of the young.

HNF1β-related MODY is one of the less common forms of MODY, with some distinctive clinical features, including atrophy of the pancreas and several forms of renal disease. HNF1β, also known as transcription factor 2 (TCF2), is involved in early stages of embryonic development of several organs, including the pancreas, where it contributes to differentiation of pancreatic endocrine Ngn3 cell progenitors from non-endocrine embryonic duct cells. The gene is on chromosome 17q.

The degree of insulin deficiency is variable. Diabetes can develop from infancy through middle adult life, and some family members who carry the gene remain free of diabetes into later adult life. Most of those who develop diabetes show atrophy of the entire pancreas, with mild or subclincal deficiency of exocrine as well as endocrine function.

The non-pancreatic manifestations are even more variable. Kidney and genitourinary malformation and diseases may occur, but inconsistently even within a family, and the specific conditions include a range of apparently unrelated anomalies and processes. The most common genitourinary condition is cystic kidney disease, but there are many varieties even of this. Renal effects begin with structural alterations (small kidneys, renal cysts, anomalies of the renal pelvis and calices), but a significant number develop slowly progressive renal failure associated with chronic cystic disease of the kidneys. In some cases, renal cysts may be detected in utero. Kidney disease may develop before or after hyperglycemia, and a significant number of people with MODY5 are discovered in renal clinics.

With or without kidney disease, some people with forms of HNF1β have had various minor or major anomalies of the reproductive system. Male defects have included epididymal cysts, agenesis of the vas deferens, or infertility due to abnormal spermatozoa. Affected women have been found to have vaginal agenesis, hypoplastic, or bicornuate uterus.

Liver enzyme elevations are common, but clinically significant liver disease is not. Hyperuricaemia and early onset gout have occurred.

The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.

It has several different types:

- type 1 - Apert syndrome

- type 2 - Crouzon syndrome

- type 3 - Saethre-Chotzen syndrome

- type 5 - Pfeiffer syndrome

A related term, "acrocephalopolysyndactyly" (ACPS), refers to the inclusion of polydactyly to the presentation. It also has multiple types:

- type 1 - Noack syndrome; now classified with Pfeiffer syndrome

- type 2 - Carpenter syndrome

- type 3 - Sakati-Nyhan-Tisdale syndrome

- type 4 - Goodman syndrome; now classified with Carpenter syndrome

- type 5 - Pfeiffer syndrome

It has been suggested that the distinction between "acrocephalosyndactyly" versus "acrocephalopolysyndactyly" should be abandoned.

The most common presentation of Milroy Disease is bilateral lower extremity lymphedema, and may also be accompanied by hydrocele.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a "primary" immunodeficiency, the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 100 recognized PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, autoinflammatory disorders, tumors, and disorders of various organs. There are currently no cures for these conditions; treatment is palliative and consists of managing infections and boosting the immune system.

Many of the physical features associated with the disorder are congenital. Characteristic craniofacial abnormalities typically include a long, narrow head that is disproportionate to the body size, a broad and prominent forehead, and a triangular-shaped face with a hypoplastic midface, pointed chin, prominent mouth, fleshy tipped upturned nose, large ears, and full lips. The teeth may be abnormally crowded together in some affected individuals.

Skeletal anomalies aren't present at birth but develop in the individual and include delayed bone maturation, slender long tubular bones, and tall vertebral bodies. Joint hyper-mobility and increased risk of hip dislocation has been presented in individuals. Abnormal spinal curvature, either kyhoscholiosis or hyperlordosis, causing back pain can also be experienced from this disorder.

Acrocephalosyndactylia (or acrocephalosyndactyly) is the common presentation of craniosynostosis and syndactyly.

Milroy's disease (MD) is a familial disease characterized by lymphedema, commonly in the legs, caused by congenital abnormalities in the lymphatic system. Disruption of the normal drainage of lymph leads to fluid accumulation and hypertrophy of soft tissues. It is also known as Milroy disease, Nonne-Milroy-Meige syndrome and hereditary lymphedema.

It was named by Sir William Osler for William Milroy, a Canadian physician, who described a case in 1892, though it was first described by Rudolf Virchow in 1863.

Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, lethargy, hypoglycemia, hypotonia, liver problems, and abnormally high levels of hyperinsulinism. Insulin controls the amount of sugar that moves from the blood into cells for conversion to energy. Individuals with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden unexpected death.

Problems related to 3-hydroxyacyl-coenzyme A dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADH deficiency) is a rare condition that prevents the body from converting certain fats to energy, particularly during fasting. Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to metabolize fats and convert them to energy. People with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency have inadequate levels of an enzyme required for a step that metabolizes groups of fats called medium chain fatty acids and short chain fatty acids; for this reason this disorder is sometimes called medium- and short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (M/SCHAD) deficiency.

Basophilia is a condition where the basophil quantity is abnormally elevated (more than 10 basophils per liter of blood). Basophilia is associated with pruritus (itching) due to the release of histamine.

The most common presentation is gastrointestinal bleed (~45% of cases), followed by abdominal pain (~43% of cases) and anemia (~15% of cases).

Onset of late infantile GM1 is typically between ages 1 and 3 years.

Neurological symptoms include ataxia, seizures, dementia, and difficulties with speech.