Screening among family members of people with known FH is cost-effective. Other strategies such as universal screening at the age of 16 were suggested in 2001. The latter approach may however be less cost-effective in the short term. Screening at an age lower than 16 was thought likely to lead to an unacceptably high rate of false positives.

A 2007 meta-analysis found that "the proposed strategy of screening children and parents for familial hypercholesterolaemia could have considerable impact in preventing the medical consequences of this disorder in two generations simultaneously." "The use of total cholesterol alone may best discriminate between people with and without FH between the ages of 1 to 9 years."

Screening of toddlers has been suggested, and results of a trial on 10,000 one-year-olds were published in 2016. Work was needed to find whether screening was cost-effective, and acceptable to families.

In 2016 the United States Preventive Services Task Force concluded that testing the general population under the age of 40 without symptoms is of unclear benefit.

Testing the general population under the age of 40 without symptoms is of unclear benefit.

The U.S. Preventive Services Task Force in 2008 strongly recommends routine screening for men 35 years and older and women 45 years and older for lipid disorders and the treatment of abnormal lipids in people who are at increased risk of coronary heart disease. They also recommend routinely screening men aged 20 to 35 years and women aged 20 to 45 years if they have other risk factors for coronary heart disease. In 2016 they concluded that testing the general population under the age of 40 without symptoms is of unclear benefit.

In Canada, screening is recommended for men 40 and older and women 50 and older. In those with normal cholesterol levels, screening is recommended once every five years. Once people are on a statin further testing provides little benefit except to possibly determine compliance with treatment.

Approximately 85% of individuals with this disorder have not been diagnosed and consequently are not receiving lipid-lowering treatments. Physical examination findings can help a physician make the diagnosis of FH. Tendon xanthomas are seen in 20-40% of individuals with FH and are pathognomonic for the condition. A xanthelasma or corneal arcus may also be seen. These common signs are supportive of the diagnosis, but are non-specific findings.

Lifestyle changes recommended for those with high cholesterol include: smoking cessation, limiting alcohol consumption, increasing physical activity, and maintaining a healthy weight.

Overweight or obese individuals can lower blood cholesterol by losing weight - on average a kilogram of weight loss can reduce LDL cholesterol by 0.8 mg/dl.

Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production. Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin), can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression.

Several different problems may lead to the diagnosis, usually by two years of age:

- seizures or other manifestations of severe fasting hypoglycemia

- hepatomegaly with abdominal protuberance

- hyperventilation and apparent respiratory distress due to metabolic acidosis

- episodes of vomiting due to metabolic acidosis, often precipitated by minor illness and accompanied by hypoglycemia

Once the diagnosis is suspected, the multiplicity of clinical and laboratory features usually makes a strong circumstantial case. If hepatomegaly, fasting hypoglycemia, and poor growth are accompanied by lactic acidosis, hyperuricemia, hypertriglyceridemia, and enlarged kidneys by ultrasound, gsd I is the most likely diagnosis. The differential diagnosis list includes glycogenoses types III and VI, fructose 1,6-bisphosphatase deficiency, and a few other conditions (page 5), but none are likely to produce all of the features of GSD I.

The next step is usually a carefully monitored fast. Hypoglycemia often occurs within six hours. A critical blood specimen obtained at the time of hypoglycemia typically reveals a mild metabolic acidosis, high free fatty acids and beta-hydroxybutyrate, very low insulin levels, and high levels of glucagon, cortisol, and growth hormone. Administration of intramuscular or intravenous glucagon (0.25 to 1 mg, depending on age) or epinephrine produces little rise of blood sugar.

The diagnosis is definitively confirmed by liver biopsy with electron microscopy and assay of glucose-6-phosphatase activity in the tissue and/or specific gene testing, available in recent years.

Without adequate metabolic treatment, patients with GSD I have died in infancy or childhood of overwhelming hypoglycemia and acidosis. Those who survived were stunted in physical growth and delayed in puberty because of chronically low insulin levels. Mental retardation from recurrent, severe hypoglycemia is considered preventable with appropriate treatment.

Hepatic complications have been serious in some patients. Adenomas of the liver can develop in the second decade or later, with a small chance of later malignant transformation to hepatoma or hepatic carcinomas (detectable by alpha-fetoprotein screening). Several children with advanced hepatic complications have improved after liver transplantation.

Additional problems reported in adolescents and adults with GSD I have included hyperuricemic gout, pancreatitis, and chronic renal failure. Despite hyperlipidemia, atherosclerotic complications are uncommon.

With diagnosis before serious harm occurs, prompt reversal of acidotic episodes, and appropriate long-term treatment, most children will be healthy. With exceptions and qualifications, adult health and life span may also be fairly good, although lack of effective treatment before the mid-1970s means information on long-term efficacy is limited.

This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasma, and premature cardiovascular disease. The incidence of this disease is about one in 500 for heterozygotes, and one in 1,000,000 for homozygotes.

HLPIIa is a rare genetic disorder characterized by increased levels of LDL cholesterol in the blood due to the lack of uptake (no Apo B receptors) of LDL particles. This pathology, however, is the second-most common disorder of the various hyperlipoproteinemias, with individuals with a heterozygotic predisposition of one in every 500 and individuals with homozygotic predisposition of one in every million. These individuals may present with a unique set of physical characteristics such as xanthelasmas (yellow deposits of fat underneath the skin often presenting in the nasal portion of the eye), tendon and tuberous xanthomas, arcus juvenilis (the graying of the eye often characterized in older individuals), arterial bruits, claudication, and of course atherosclerosis. Laboratory findings for these individuals are significant for total serum cholesterol levels two to three times greater than normal, as well as increased LDL cholesterol, but their triglycerides and VLDL values fall in the normal ranges. To manage persons with HLPIIa, drastic measures may need to be taken, especially if their HDL cholesterol levels are less than 30 mg/dL and their LDL levels are greater than 160 mg/dL. A proper diet for these individuals requires a decrease in total fat to less than 30% of total calories with a ratio of monounsaturated:polyunsaturated:saturated fat of 1:1:1. Cholesterol should be reduced to less than 300 mg/day, thus the avoidance of animal products and to increase fiber intake to more than 20 g/day with 6g of soluble fiber/day. Exercise should be promoted, as it can increase HDL. The overall prognosis for these individuals is in the worst-case scenario if uncontrolled and untreated individuals may die before the age of 20, but if one seeks a prudent diet with correct medical intervention, the individual may see an increased incidence of xanthomas with each decade, and Achilles tendinitis and accelerated atherosclerosis will occur.

Weight loss and dietary modification are effective first-line lifestyle modification treatments for hypertriglyceridemia. For people with mildly or moderately high levels of triglycerides lifestyle changes including weight loss and dietary modification are recommended. This may include restriction of carbohydrates (specifically fructose) and fat in the diet. Medications are recommended in those with high levels of triglycerides that are not corrected with the aforementioned lifestyle modifications, with fibrates being recommended first.

The decision to treat hypertriglyceridemia with medication depends on the levels and on the presence of other risk factors for cardiovascular disease. Very high levels that would increase the risk of pancreatitis is treated with a drug from the fibrate class. Niacin and omega-3 fatty acids as well as drugs from the statin class may be used in conjunction, with statins being the main medication for moderate hypertriglyceridemia when reduction of cardiovascular risk is required.

Diagnosis is made comprehensively, together with visual observation, body fat assessment, a review of lab panels consisting of A1c, glucose, lipid, and patient history.

Caliper measurements of skinfold thickness is recommended to quantify fat loss as a supportive information. In this measurement, skinfold thickness of less than 10mm for men and 22mm for women at the anterior thigh is suggestive cutoff for the diagnosis of lipodystrophy. Less commonly, biphotonic absorptiometry and magnetic resonance imaging (MRI) can be done for the measurement of body fat.

Other forms of insulin resistance may be assessed for differential diagnosis. Resistance to conventional therapy for hyperglycemia and hypertriglyceridemia serves as an indication for lipodystrophy. Specifically, the diagnosis is strongly considered for those requiring ≥200 units/day of insulin and persistent elevation of ≥250 mg/dl of triglyceride levels.

The use of leptin levels should be carefully approached. While low leptin levels are helpful for making the diagnosis, they are not specific for the lipodystrophy. High leptin levels can help excluding the possible lipodystrophy, but there is no well-established standardized leptin ranges.

Vitamin E supplements have shown to help children with the deficiency.

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.

In some forms of MODY, standard treatment is appropriate, though exceptions occur:

- In MODY2, oral agents are relatively ineffective and insulin is unnecessary.

- In MODY1 and MODY3, insulin may be more effective than drugs to increase insulin sensitivity.

- Sulfonylureas are effective in the K channel forms of neonatal-onset diabetes. The mouse model of MODY diabetes suggested that the reduced clearance of sulfonylureas stands behind their therapeutic success in human MODY patients, but Urbanova et al. found that human MODY patients respond differently to the mouse model and that there was no consistent decrease in the clearance of sulfonylureas in randomly selected HNF1A-MODY and HNF4A-MODY patients.

Combined hyperlipidemia (or -aemia) (also known as multiple-type hyperlipoproteinemia) is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electrophoresis (a test now rarely performed) it shows as a hyperlipoproteinemia type IIB. It is the most commonly inherited lipid disorder, occurring in around one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 have this disorder.

The elevated triglyceride levels (>5 mmol/l) are generally due to an increase in very low density lipoprotein (VLDL), a class of lipoproteins prone to cause atherosclerosis.

Around 80 cases have been reported in the literature worldwide, hence this condition appears to be relatively rare. More than likely, sitosterolemia is significantly underdiagnosed and many patients are probably misdiagnosed with hyperlipidemia.

Initial and general approach for AGL patients are to treat the metabolic complications such as leptin-replacement therapy and/or to control the abnormal levels of lipids or glucose levels. Anti-diabetic medications such as insulin, metformin, or thiazolidinediones are used for insulin-resistance or high glucose levels, or statins or fibrates are used for hyperlipidemia. If symptoms persist, metreleptin can be prescribed.

Metreleptin (MYALEPT) is a recombinant human leptin analog and was approved by FDA in 2014 for generalized lipodystrophy as an adjunct therapy to diet to treat the complication of leptin deficiency. It is the only drug option approved for generalized lipodystrophy-related symptoms and is not intended to use for patients with HIV-related lipodystrophy or complications of partial lipodystrophy. Although it is a recombinant human leptin analog, it is not completely the same as natural leptin as it is produced in "e. coli" and has added methionine residues at is amino terminus. It works by binding to the human leptin receptor, ObR, and activates the receptor. The receptor belongs to the Class I cytokine family and signals the JAK/STAT pathway. It is available as 11.3 mg powder in a vial for subcutaneous injection upon reconstitution and needs to be protected from the light. For treatment, patients and their doctors need to be enrolled and certified in the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program because people on this treatment has a risk of developing anti-metreleptin antibodies that decrease the effectiveness of metreleptin, and increased risk of lymphoma. Clinical study with GL patients who took metreleptin had increased insulin sensitivity, as indicated by decreased HbA1c and fasting glucose level, and reduced caloric intake as well as fasting triglyceride levels.

Plasmapheresis was previously an option for lowering extremely high triglyceride levels for preventing pancreatitis and painful xanthoma, but its use has been decreased after the approval of metreleptin.

Cosmetic treatments, such as facial reconstruction or implants, can be done to replace adipose tissues.

Lifestyle modifications are also recommended, including changes into less fat diet and exercise.

The prognosis of the disease is unknown as of December, 2017.

The disorder is treated by strictly reducing the intake of foods rich in plant sterols (e.g., vegetable oils, olives and avocados). However, dietary therapy is often never fully sufficient to control this disease since plant sterols are constituents of all plant-based foods. Statins have been used, and while these lower cholesterol levels and may ameliorate atherosclerotic disease, plant sterol levels are insufficiently lowered by their use alone.

If dietary treatment alone is insufficient, bile acid-binding resins (e.g., cholestyramine, colestipol) could be considered. In October 2002, a new cholesterol absorption inhibitor, ezetimibe, received US Food and Drug Administration (FDA) approval for use in sitosterolemia. This drug is now the standard of care, as it blocks sterol entry and can be used in combination with bile-acid resins.

Finally, ileal bypass has been performed in select cases to decrease the levels of plant sterols in the body, though this therapy was undertaken prior to the advent of ezetimibe.

The initial workup of abetalipoproteinemia typically consists of stool sampling, a blood smear, and a fasting lipid panel though these tests are not confirmatory. As the disease is rare, though a genetics test is necessary for diagnosis, it is generally not done initially.

Acanthocytes are seen on blood smear. Since there is no or little assimilation of chylomicrons, their levels in plasma remains low.

The inability to absorb fat in the ileum will result in steatorrhea, or fat in the stool. As a result, this can be clinically diagnosed when foul-smelling stool is encountered. Low levels of plasma chylomicron are also characteristic.

There is an absence of apolipoprotein B. On intestinal biopsy, vacuoles containing lipids are seen in enterocytes. This disorder may also result in fat accumulation in the liver (hepatic steatosis). Because the epithelial cells of the bowel lack the ability to place fats into chylomicrons, lipids accumulate at the surface of the cell, crowding the functions that are necessary for proper absorption.

There are drugs that can increase serum HDL such as niacin or gemfibrozil. While these drugs are useful for patients with hyperlipidemia, Tangier's disease patients do not benefit from these pharmaceutical interventions.

Therefore, the only current treatment modality for Tangier's disease is diet modification. A low-fat diet can reduce some of the symptoms, especially those involving neuropathies.

In the setting of critical illness, low cholesterol levels are predictive of clinical deterioration, and are correlated with altered cytokine levels.

In humans with genetic loss-of-function variants in one copy of the "ANGPTL3" gene, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of "ANGPTL3", low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia").

Hooft disease is a rare condition evidenced by low blood lipid level, red rash and mental and physical retardation.

Acanthosis nigricans is typically diagnosed clinically. A skin biopsy may be needed in unusual cases. If no clear cause is obvious, it may be necessary to search for one. Blood tests, an endoscopy, or X-rays may be required to eliminate the possibility of diabetes or cancer as the cause.

On biopsy, hyperkeratosis, epidermal folding, leukocyte infltration, and melanocyte proliferation may be seen.

Acanthosis nigricans should be distinguished from the casal collar appearing in pellagra.

High-density lipoproteins are created when a protein in the bloodstream, Apolipoprotein A1 (apoA1), combines with cholesterol and phospholipids. The cholesterol and phospholipids used to form HDL originate from inside cells but are transported out of the cell into the blood via the ABCA1 transporter. People with Tangier disease have defective ABCA1 transporters resulting in a greatly reduced ability to transport cholesterol out of their cells, which leads to an accumulation of cholesterol and phospholipids in many body tissues, which can cause them to increase in size. Reduced blood levels of high-density lipoproteins is sometimes described as hypoalphalipoproteinemia.

People affected by this condition also have slightly elevated amounts of fat in the blood (mild hypertriglyceridemia) and disturbances in nerve function (neuropathy). The tonsils are visibly affected by this disorder; they frequently appear orange or yellow and are extremely enlarged. Affected people often develop premature atherosclerosis, which is characterized by fatty deposits and scar-like tissue lining the arteries. Other signs of this condition may include an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly), clouding of the cornea, and early-onset cardiovascular disease.

Tangier disease is a rare disorder with approximately 50 cases identified worldwide. This disorder was originally discovered on Tangier Island off the coast of Virginia, but has now been identified in people from many different countries.