Familial partial lipodystrophy (FPL), also known as Köbberling–Dunnigan syndrome, is a rare genetic metabolic condition characterized by the loss of subcutaneous fat.

FPL also refers to a rare metabolic condition in which there is a loss of subcutaneous fat in the arms, legs and lower torso. The upper section of the body, face, neck, shoulders, back and trunk carry an excess amount of fat.

As the body is unable to store fat correctly this leads to fat around all the vital organs and in the blood (triglycerides). This results in heart problems, cirrhosis of the liver, lipoatrophic diabetes, and pancreatitis, along with various other complications.

Dunnigan-type familial partial lipodystrophy, also known as FPLD Type II and abbreviated as (FPLD2), is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes usually type 2, dyslipidemia, hypertension, and early endpoints of atherosclerosis. It can also result in hepatic steatosis. FPLD results from mutations in LMNA gene, which is the gene that encodes nuclear lamins A and C.

The clinical presentation is similar to people with congenital lipodystrophy: the only difference is that AGL patients are born with normal fat distribution and symptoms develop in childhood and adolescence years and rarely begins after 30 years of age. Females are more often affected than males, with ratio being 3:1.

The hallmark characteristics are widespread loss of subcutaneous fat, ectopic fat deposition, leptin deficiency, and severe metabolic abnormalities such as insulin resistance. Subcutaneous fat loss in AGL patients are visible in all parts of the body. AGL mostly affects face and the extremities and may look sunken or swollen in the eyes. However, the degree and location of severity may vary by person. Especially, intra-abdominal fat loss is variable. As subcutaneous fat is lost, affected areas show prominent structures of veins and muscle. Those with panniculitis-associated AGL may present erythematous nodules.

Metabolic complications include insulin resistance, high metabolic rate, and uncontrolled lipid levels such as hypertriglyceridemia, low HDL, and high LDL. Patients may develop diabetes mellitus secondary to insulin resistance.

Recent case reports reveled that lymphoma is present in some patients but its prevalence is not known at this time.

Acquired generalized lipodystrophy (also known as "Lawrence syndrome," and "Lawrence–Seip syndrome", abbreviation: AGL) is a rare skin condition that appears during childhood or adolescence, characterized by fat loss affecting large areas of the body, particularly the face, arms, and legs. There are 4 types of lipodystrophy based on its onset and areas affected: acquired or inherited (congenital or familial), and generalized or partial. Both acquired or inherited lipodystrophy present as loss of adipose tissues. The near-total loss of subcutaneous adipose tissue is termed generalized lipodystrophy while the selective loss of adipose tissues is denoted as partial lipodystrophy. Thus, as the name suggests, AGL is a near-total deficiency of adipose tissues in the body that is developed later in life. It is an extremely rare disease that only about 100 cases are reported worldwide. There are three main etiologies of AGL suspected: autoimmune, panniculitis-associated, or idiopathic. After its onset, the disease progresses over a few days, weeks, months, or even in years. Clinical presentations of AGL are similar to other lipodystrophies, including metabolic complications and hypoleptinemia. Treatments are also similar and mainly supportive for symptomatic alleviation. Although HIV- or drug-induced lipodystrophy are a type of acquired lipodystrophy, its origin is very specific and distinct hence is usually not discussed with AGL (see HIV-Associated Lipodystrophy).

Morgagni Stewart Morel syndrome (metabolic craniopathy ) is a condition with a wide range of associated endocrine problems including: diabetes mellitus, diabetes insipidus, and hyperparathyroidism. Other signs and symptoms include headaches, vertigo, hirsutism, menstrual problems, galactorrhoea, obesity, depression, and seizures. Thickening of the inner table of the frontal part of the skull a usually benign condition known as hyperostosis frontalis interna. The syndrome was first described in 1765. It's named after the Italian anatomist and pathologist Giovanni Battista Morgagni.

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.

The main sign of metabolic syndrome is central obesity (also known as visceral, male-pattern or apple-shaped adiposity), overweight with adipose tissue accumulation particularly around the waist and trunk.

Other signs of metabolic syndrome include high blood pressure, decreased fasting serum HDL cholesterol, elevated fasting serum triglyceride level (VLDL triglyceride), impaired fasting glucose, insulin resistance, or prediabetes.

Associated conditions include hyperuricemia, fatty liver (especially in concurrent obesity) progressing to nonalcoholic fatty liver disease, polycystic ovarian syndrome (in women), erectile dysfunction (in men), and acanthosis nigricans.

The variable presentation of ROHHAD includes the following main symptoms:

- Hyperphagia and obesity by age of 10 years - (median age 3 years);

- Respiratory Manifestations:

- Alveolar Hypoventilation (median onset age 6.2 years);

- Cardiorespiratory arrest;

- Reduced Carbon Dioxide Ventilatory Response;

- Obstructive sleep apnea.

- Thermal or other hypothalamic dysregulations, with autonomic dysregulation by median age 3.6 years:

- Failed Growth Hormone Stimulation;

- Adipsic hypernatremia (inability to feel thirst to keep normal hydration);

- Hypernatremia;

- Hyperprolactinemia;

- Hyperphagia;

- Diabetes insipidus;

- Ophthalmologic Manifestations;

- Thermal Dysregulation;

- Gastrointestinal dysmotility;

- Altered Perception of Pain;

- Altered Sweating;

- Cold Hands and Feet.

- Neurobehavioral disorders;

- Tumors of neural crest origin.

Clinically overlapping cases exist because CCHS phenotype can also include autonomic nervous system dysregulation, or tumors of neural crest origin.

"Maturity onset diabetes of the young" (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. MODY is often referred to as "monogenic diabetes" to distinguish it from the more common types of diabetes (especially type 1 and type 2), which involve more complex combinations of causes involving multiple genes and environmental factors. MODY 2 and MODY 3 are the most common forms. MODY should not be confused with latent autoimmune diabetes of adults (LADA) — a form of type 1 DM, with slower progression to insulin dependence than child-onset type 1 DM, and which occurs later in life.

Prediabetes typically has no distinct signs or symptoms except the sole sign of high blood sugar. Patients should monitor for signs and symptoms of type 2 diabetes mellitus. These include the following:

- Constant hunger

- Unexplained weight loss

- Weight gain

- Flu-like symptoms, including weakness and fatigue

- Blurred vision

- Slow healing of cuts or bruises

- Tingling or loss of feeling in hands or feet

- Recurring gum or skin infections

- Recurring vaginal or bladder infections

- A high BMI (Body Mass Index) result

High-sensitivity C-reactive protein has been developed and used as a marker to predict coronary vascular diseases in metabolic syndrome, and it was recently used as a predictor for nonalcoholic fatty liver disease (steatohepatitis) in correlation with serum markers that indicated lipid and glucose metabolism. Fatty liver disease and steatohepatitis can be considered as manifestations of metabolic syndrome, indicative of abnormal energy storage as fat in ectopic distribution.

Reproductive disorders (such as polycystic ovary syndrome in women of reproductive age), and erectile dysfunction or decreased total testosterone (low testosterone-binding globulin) in men can be attributed to metabolic syndrome.

Some of the possible symptoms that can occur with metabolic disorders are: lethargy, weight loss, jaundice, seizures, to name a few. The symptoms expressed would vary with the type of metabolic disorder. There are four categories of symptoms: acute symptoms, late-onset acute symptoms, progressive general symptoms and permanent symptoms.

Symptoms for Alström syndrome generally appear during infancy with great variability in age. Some of the symptoms include:

- Heart failure (Dilated cardiomyopathy) in over 60% of cases, usually within the first few weeks after birth, but sometimes the onset is in adolescence or adulthood.

- Light sensitivity and vision problems (Cone-rod dystrophy) in all cases, usually within 15 months of birth and progressively worsening until about 20 years of age

- Delays in early, developmental milestones in 50% of cases, learning disabilities in about 30% of cases

- Obesity in 100% of cases, apparent by 5 years of age, but often apparent in infancy (Alström infants usually have normal birth weights, and by adolescence, weights tend to be in the high-normal to normal range)

- Nystagmus (usually affects the children) one of the first symptoms to occur which causes involuntary rapid eye movement.

- Heart failure (Dilated cardiomyopathy) in over 60% of cases, usually within the first few weeks after birth, but sometimes the onset is in adolescence or adulthood.(chronic)

- Mild to moderate bilateral sensorineural hearing loss.

- Type 2 diabetes usually occurs in early childhood.

- Hyperinsulinemia/ insulin resistance—development of high level of insulin in blood.

- Steatosis (fatty liver) and elevated transaminases (liver enzymes) often develop in childhood and can progress in some patients to cirrhosis and liver failure.

- Endocrine dysfunctions may occur where the patient may experience an under or over active thyroid gland, weak growth hormone, increased androgen in females, and low testosterone in males.

- Slowly progressive kidney failure can occur in the second to fourth decade of life.

CCD causes persistent secretory diarrhea. In a fetus, it leads to polyhydramnios and premature birth. Immediately after birth, it leads to dehydration, hypoelectrolytemia, hyperbilirubinemia, abdominal distention, and failure to thrive.

Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD syndrome) is a very rare disease affecting approximately 75 people worldwide. Patients with ROHHAD, as well as patients with congenital central hypoventilation syndrome (CCHS) have damage to the mechanism governing proper breathing. ROHHAD syndrome is a disease that is potentially lethal and incurable. Fifteen patients with ROHHAD were evaluated by Diego Ize-Ludlow et al. work published in 2007.

Impaired glucose tolerance (IGT) is a pre-diabetic state of dysglycemia, that is associated with insulin resistance and increased risk of cardiovascular pathology. IGT may precede type 2 diabetes mellitus by many years. IGT is also a risk factor for mortality.

Marshall JD et al. provided a comprehensive guidance for diagnostic criteria in their 2007 publication.

Birth – 2 years:

Minimum diagnosis requires 2 major criteria or 1 major and 2 minor criteria.

Major criteria are:

1. ALMS1 mutation in 1 allele and/or family history of Alström Syndrome

2. Vision pathology (nystagmus, photophobia).

Minor criteria are:

1. Obesity

2. Dilated cardiomyopathy with congestive heart failure.

Other variable supportive evidence:

Recurrent pulmonary infections, normal digits, delayed developmental milestones.

At 3–14 years of age:

2 major criteria or 1 major and 3 minor criteria.

Major criteria are:

1. ALMS1 mutation in 1 allele and/or family history of Alström Syndrome,

2. Vision pathology (nystagmus, photophobia, diminished acuity). If old enough for testing: cone dystrophy by ERG.

Minor Criteria:

1. Obesity and/or insulin resistance and/or Type 2 Diabetes

2. History of dilated cardiomyopathy with congestive heart failure

3. Hearing loss

4. Hepatic dysfunction

5. Renal failure

6. Advanced bone age

Variable supportive evidence:

Recurrent pulmonary infections, normal digits, delayed developmental milestones, hyperlipidemia, scoliosis, flat wide feet

hypothyroidism, hypertension, recurrent urinary tract infection, growth hormone deficiency.

Presentation 15 years – adulthood:

2 major and 2 minor criteria or 1 major and 4 minor criteria.

Major criteria are:

1) ALMS1 mutation in 1 allele and/or family history of Alström Syndrome.

2) Vision pathology (history of nystagmus in infancy/childhood, legal blindness, cone and rod dystrophy by ERG).

Minor criteria:

1) Obesity and/or insulin resistance and/or Type 2 Diabetes

2) History of dilated cardiomyopathy with congestive heart failure.

3) Hearing loss

4) Hepatic dysfunction

5) Renal failure

6) Short stature

7) Males: hypogonadism, Females: irregular menses and/or hyperandrogenism

Other supportive features:

Recurrent pulmonary infections, normal digits, history of developmental delay, hyperlipidemia, scoliosis, flat wide feet,

hypothyroidism, hypertension, recurrent urinary tract infections/urinary dysfunction, growth hormone deficiency, alopecia.

A mutations in a number of genes have been associated with this condition. Mutations associated with FPL have been reported in "LMNA" (lamin A/C), "PPARG" (PPARγ), "AKT2" (AKT serine/threonine kinase 2), "PLIN1" (perilipin-1), and "CIDEC" (cell-death-inducing DFFA-like effector B).

Six types (1-6) have been described. Types 1-5 are inherited in an autosomal dominant fashion.

Type 1 (Kobberling variety, FPL1) is very rare and has only been reported in women to date. Fat loss is confined to the limbs and mostly in the distal parts. Central obesity may be present. Complications include hypertension, insulin resistance and hypertriglyceridemia. The gene causing this condition is not yet known. This form was first described in 1975.

Type 2 (Dunnigan Variety, FPL2) is the most common form and is due to mutations in the LMNA gene. Over 500 cases have been reported to date. Development up to puberty is normal. Fat is then gradually lost in is the limbs and trunk. Fat may accumulate around the face and between the shoulder blades. Insulin resistance is common. Other conditions associated with this condition include acanthosis nigricans, fatty liver, hypertriglyceridemia and polycystic ovary syndrome in women. There is an increased risk of coronary heart disease. Cardiomyopathy and muscular dystrophy may occur rarely. Xanthoma and nail changes may occur.

Type 3 is due to mutations in the PPARG gene. It is rare with approximately 30 cases reported to date. It is similar to type 2 but tends to be milder.

Type 4 is due to mutations in the PLIN1 gene. It is rare with only a small number of cases reported. Fat loss tends to affect the lower limbs and buttocks. Insulin resistance and hypertriglyceridemia occur. Calf muscular hypertrophy may occur.

Type 5 is due to mutations in the AKT2 gene. It has been reported in four patients all members of the same family. Fat loss affects the upper and lower limbs. The patients also suffered from hypertension, insulin resistance and hypertriglyceridemia.

Type 6 due to mutations in the CIDEC gene. It is inherited in an autosomal recessive fashion and has been reported in only one patient to date. Features included fat loss, severe insulin resistance, fatty liver, acanthosis nigricans and diabetes.

There are often no visible symptoms of hyperinsulinemia unless hypoglycaemia (low blood sugar) is present.

Some patients may experience a variety of symptoms when hypoglycaemia is present, including:

- Temporary muscle weakness

- Brain fog

- Fatigue

- Temporary thought disorder, or inability to concentrate

- Visual problems such as blurred vision or double vision

- Headaches

- Shaking/Trembling

- Thirst

If a person experiences any of these symptoms, a visit to a qualified medical practitioner is advised, and diagnostic blood testing may be required.

Lipodystrophy is a disorder in which the body is unable to produce fat. The medical condition is characterized by abnormal or degenerative conditions of the body's adipose tissue. ("Lipo" is Greek for "fat", and "dystrophy" is Greek for "abnormal or degenerative condition".) A more specific term, "lipoatrophy", is used when describing the loss of fat from one area (usually the face). This condition is also characterized by a lack of circulating leptin which may lead to osteosclerosis.

These depend on poorly understood variations in individual biology and consequently may not be found with all people diagnosed with insulin resistance.

- Increased hunger

- Lethargy (tiredness)

- Brain fogginess and inability to focus

- High blood sugar

- Weight gain, fat storage, difficulty losing weight – for most people, excess weight is from high subcutaneous fat storage; the fat in IR is generally stored in and around abdominal organs in both males and females; it is currently suspected that hormones produced in that fat are a precipitating cause of insulin resistance

- Increased blood cholesterol levels

- Increased blood pressure; many people with hypertension are either diabetic or pre-diabetic and have elevated insulin levels due to insulin resistance; one of insulin's effects is to control arterial wall tension throughout the body

Normal weight obesity is the condition of having normal body weight, but with a high body fat percentage, leading to some of the same health risks as obesity.

Hyperlipoproteinemia type II, by far the most common form, is further classified into types IIa and IIb, depending mainly on whether elevation in the triglyceride level occurs in addition to LDL cholesterol.

Inherited metabolic disorders are one cause of metabolic disorders, and occur when a defective gene causes an enzyme deficiency. These diseases, of which there are many subtypes, are known as inborn errors of metabolism. Metabolic diseases can also occur when the liver or pancreas do not function properly.

Accessory pancreas is a rare condition in which small groups of pancreatic cells are separate from the pancreas. They may occur in the mesentery of the small intestine, the wall of the duodenum, the upper part of the jejunum, or more rarely, in the wall of the stomach, ileum, gallbladder or spleen. The condition was first described by Klob in 1859.

Accessory pancreas is a small cluster of pancreas cells detached from the pancreas and sometimes found in the wall of the stomach or intestines.