The diagnosis of the disease is mainly clinical (see diagnostic criteria). A laboratory workup is needed primarily to investigate for the presence of associated disorders (metabolic, autoimmune, and renal diseases).

- Every patient should have a fasting blood glucose and lipid profile, creatinine evaluation, and urinalysis for protein content at the first visit, after which he/she should have these tests on a regular basis.

- Although uncommon, lipid abnormalities can occur in the form of raised triglyceride levels and low high-density lipoprotein cholesterol levels.

- Patients usually have decreased serum C3 levels, normal levels of C1 and C4, and high levels of C3NeF (autoantibody), which may indicate the presence of renal involvement.

- Antinuclear antibodies (ANA) and antidouble-stranded deoxyribonucleic acid (DNA) antibodies have reportedly been observed in some patients with acquired partial lipodystrophy.

- A genetic workup should be performed if the familial form of lipodystrophy is suggested.

Laboratory work for associated diseases includes:

- Metabolic disease - fasting glucose, glucose tolerance test, lipid profile, and fasting insulin to characterize the insulin resistance state; free testosterone (in women) to look for polycystic ovary syndrome.

- Autoimmune disease - ANA, antidouble-stranded DNA, rheumatoid factor, thyroid antibodies, C3, and C3NeF.

As a confirmatory test, whole-body MRI usually clearly demonstrates the extent of lipodystrophy. MRI is not recommended on a routine basis.

Medical diagnosis of CGL can be made after observing the physical symptoms of the disease: lipoatrophy (loss of fat tissues) affecting the trunk, limbs, and face; hepatomegaly; acromegaly; insulin resistance; and high serum levels of triglycerides. Genetic testing can also confirm the disease, as mutations in the AGPAT2 gene is indicative of CGL1, a mutation in the BSCL2 gene is indicative of CGL2, and mutations in the CAV1 and PTRF genes are indicative of CGL3 and CGL4 respectively. Physical diagnosis of CGL is easier, as CGL patients are recognizable from birth, due to their extreme muscular appearance, which is caused by the absence of subcutaneous fat.

CGL3 patients have serum creatine kinase concentrations much higher than normal (2.5 to 10 times the normal limit). This can be used to diagnose type 3 patients and differentiate them from CGL 1 and 2 without mapping their genes. Additionally, CGL3 patients have low muscle tone when compared with other CGL patients.

This condition can be diagnosed by genetic testing. Furthermore, an echocardiogram and X-ray may help in the diagnosis.

A review published in 2004, which was based on 35 patients seen by the respective authors over 8 years and also a literature review of 220 cases of acquired partial lipodystrophy (APL), proposed an essential diagnostic criterion. Based on the review and the authors experience, they proposed that APL presents as a gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the "cephalocaudal" sequence, sparing the lower extremities. The median age of the onset of lipodystrophy was seven years. Several autoimmune diseases, in particular systemic lupus erythematosus and dermatomyositis, were associated with APL. The prevalence rates of diabetes mellitus and impaired glucose tolerance were 6.7% and 8.9%, respectively. Around 83% of APL patients had low complement 3 (C3) levels and the presence of polyclonal immunoglobulin C3 nephritic factor. About 22% of patients developed membranoproliferative glomerulonephritis (MPGN) after a median of about 8 years following the onset of lipodystrophy. Compared with patients without renal disease, those with MPGN had earlier age of onset of lipodystrophy (12.6 ± 10.3 yr vs 7.7 ± 4.4 yr, respectively; p < 0.001) and a higher prevalence of C3 hypocomplementemia (78% vs 95%, respectively; p = 0.02).

The adipose stores of the gluteal regions and lower extremities (including soles) tend to be either preserved or increased, particularly among women. Variable fat loss of the palms, but no loss of intramarrow or retro-orbital fat, has been demonstrated.

The differential diagnosis of this condition consists of:

- Hypertrophic cardiomyopathy

- Beckwith-Wiedemann syndrome

- Berardinelli-Seip congenital lipodystrophy

CGL patients have to maintain a strict diet for life, as their excess appetite will cause them to overeat. Carbohydrate intake should be restricted in these patients. To avoid chylomicronemia, CGL patients with hypertriglyceridemia need to have a diet very low in fat. CGL patients also need to avoid total proteins, trans fats, and eat high amounts of soluble fiber to avoid getting high levels of cholesterol in the blood.

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.

Many people with MDP syndrome are high achievers intellectually following careers in law, medicine and computing. A crucial point is that they do not have progeria and there is no evidence of accelerated intellectual decline with age in these patients. Equally life expectancy has not been shown to be reduced. Patients of 65 have been described in the literature and none of the patients are known to have malignancy. Therefore, there are many crucial differences with progeria and the name of progeroid in the title is confusing as this really refers to the lack of fat in the face and taut skin and not any intellectual or other age associated features.

This not known with certainty but is estimated to be about one per million. It appears to be more common in females than males.

As fat cannot be stored under the skin it is important to have a healthy diet without excess fat. Often due to failure to thrive or lack of subcutaneous fat there may have been encouragement to add supplements or fat to the diet however this will not result in any increase in fat under the skin and can easily result in it going into tissues such as the liver or kidney where it is not desired. In people with moderate / severe lipodystrophy a low fat diet would be recommended but in those where the lipodystrophy has not progressed (for example in younger children) a healthy relatively low fat diet may be sufficient. The fat and muscle reduction is not the result of dietary insufficiency and cannot be treated with dietary measures. Apart from diet the other thing that is important is exercise which should be encouraged and will make insulin work more effectively.

In those who have not developed diabetes it is recommended fasting insulin, triglycerides, glucose and HbA1c should be measured annually to monitor insulin resistance and blood glucose.

In those with diabetes it is suggested using Metformin in doses of at least 2g/day as it decreases insulin resistance and improves insulin sensitivity, following appropriate clinical consultation.

The thin skin means if there is trauma there should be rapid attention to any wounds to avoid infection and help primary healing as there can be problems with skin ulcers.

There are several treatments available for bleeding due to factor X deficiency, however a specifi FX concentrate is not available (2009).

1. Prothrombin complex concentrate (PCC) supplies FX with a risk of thrombosis.

2. Fresh frozen plasma (FFP): This is relatively inexpensive and readily available. While effective this treatment carries a risk of blood-borne viruses and fluid overload.

3. If vitamin K levels are low, vitamin K can be supplied orally or parenterally.

Treatment of FX deficiency in amyloidosis may be more complex and involve surgery (splenectomy) and chemotherapy.

Reversion of lipodystrophy does not occur after withdrawal of protease inhibitors.

A lipodystrophy can be a lump or small dent in the skin that forms when a person performs injections repeatedly in the same spot. These types of lipodystrophies are harmless and can be avoided by changing (rotating) the locations of injections. For those with diabetes, using purified insulins may also help.

One of the side-effects of lipodystrophy is the rejection of the injected medication, the slowing down of the absorption of the medication, or trauma that can cause bleeding that, in turn, will reject the medication. In any of these scenarios, the dosage of the medication, such as insulin for diabetics, becomes impossible to gauge correctly and the treatment of the disease for which the medication is administered is impaired, thereby allowing the medical condition to worsen.

In some cases, rotation of the injection sites may not be enough to prevent lipodystrophy.

Blood tests are needed to differentiate FX deficiency from other bleeding disorders. Typical are normal thrombin time, prolonged prothrombin time (PT) and prolonged partial thromboplastin time(PTT). FX antigen and its coagulant activity can be used to classify the severity of the condition:

1. Type I has low levels of FX antigen and activity.

2. Type II has low coagulant activity but normal or borderline FX antigen levels.

The FX (F10) gene is found on chromosome 13q34. Heterogeneous mutations have been described in FX deficient patients.

GHRH analogs such as tesamorelin can be used to treat HIV-associated lipodystrophy.

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.

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.

Lipodystrophy can be caused by metabolic abnormalities due to genetic issues. These are often characterized by insulin resistance and are associated with metabolic syndrome.

In terms of diagnosis of Fukuyama congenital muscular dystrophy, serum creatine kinase concentration and muscle biopsies can be obtained to help determine if the individual has FMCD. FKTN molecular genetic testing is used to determine a mutation in the FKTN gene after a serum creatine kinase concentration, muscle biopsies, and/or MRI imaging have presented abnormalities indicative of FCMD, the presence of the symptoms indicates Fukuyama congenital muscular dystrophy. The available genetic test include:

- Linkage analysis

- Deletion analysis

- Sequence analysis - exons

- Sequence analysis - entire coding region

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 basic tests performed when an immunodeficiency is suspected should include a full blood count (including accurate lymphocyte and granulocyte counts) and immunoglobulin levels (the three most important types of antibodies: IgG, IgA and IgM).

Other tests are performed depending on the suspected disorder:

- Quantification of the different types of mononuclear cells in the blood (i.e. lymphocytes and monocytes): different groups of T lymphocytes (dependent on their cell surface markers, e.g. CD4+, CD8+, CD3+, TCRαβ and TCRγδ), groups of B lymphocytes (CD19, CD20, CD21 and Immunoglobulin), natural killer cells and monocytes (CD15+), as well as activation markers (HLA-DR, CD25, CD80 (B cells).

- Tests for T cell function: skin tests for delayed-type hypersensitivity, cell responses to mitogens and allogeneic cells, cytokine production by cells

- Tests for B cell function: antibodies to routine immunisations and commonly acquired infections, quantification of IgG subclasses

- Tests for phagocyte function: reduction of nitro blue tetrazolium chloride, assays of chemotaxis, bactericidal activity.

Due to the rarity of many primary immunodeficiencies, many of the above tests are highly specialised and tend to be performed in research laboratories.

Criteria for diagnosis were agreed in 1999. For instance, an antibody deficiency can be diagnosed in the presence of low immunoglobulins, recurrent infections and failure of the development of antibodies on exposure to antigens. The 1999 criteria also distinguish between "definitive", "probable" and "possible" in the diagnosis of primary immunodeficiency. "Definitive" diagnosis is made when it is likely that in 20 years, the patient has a >98% chance of the same diagnosis being made; this level of diagnosis is achievable with the detection of a genetic mutation or very specific circumstantial abnormalities. "Probable" diagnosis is made when no genetic diagnosis can be made, but the patient has all other characteristics of a particular disease; the chance of the same diagnosis being made 20 years later is estimated to be 85-97%. Finally, a "possible" diagnosis is made when the patient has only some of the characteristics of a disease are present, but not all.

Lipomatosis is believed to be an autosomal dominant condition in which multiple lipomas are present on the body. Many discrete, encapsulated lipomas form on the trunk and extremities, with relatively few on the head and shoulders. In 1993, a genetic polymorphism within lipomas was localized to chromosome 12q15, where the HMGIC gene encodes the high-mobility-group protein isoform I-C. This is one of the most commonly found mutations in solitary lipomatous tumors but lipomas often have multiple mutations. Reciprocal translocations involving chromosomes 12q13 and 12q14 have also been observed within.

Although this condition is benign, it can sometimes be very painful depending on location of the lipomas. Some patients who are concerned with cosmetics seek removal of individual lipomas. Removal can include simple excision, endoscopic removal, or liposuction.

Other entities which are accompanied by multiple lipomas include Proteus syndrome, Cowden syndrome and related disorders due to PTEN gene mutations, benign symmetric lipomatosis (Madelung disease),Dercum's Disease, familial lipodystrophy, hibernomas, epidural steroid injections with epidural lipomatosis, and familial angiolipomatosis.

Unlike other autoinflammatory disorders, patients with CANDLE do not respond to IL-1 inhibition treatment in order to stop the autoinflammatory response altogether. This suggests that the condition also involves IFN dysregulation.

Microlissencephaly can be diagnosed by prenatal MRI. MRI is better than ultrasound when it comes to detecting microlissencephaly or MSGP prenatally.

The ideal time for proper prenatal diagnosis is between the 34th and 35th gestational week which is the time when the secondary gyration normally terminates. In microlissencephaly cases, the primary sulci would be unusually wide and flat while secondary sulci would be missing.

At birth, lissencephaly with a head circumference of less than minus three standard deviations (< –3 SD) is considered microlissencephaly.

Although genetic diagnosis in patients with MLIS is challenging, exome sequencing has been suggested to be a powerful diagnostic tool.

Marfanoid–progeroid–lipodystrophy syndrome (MPL), also known as Marfan lipodystrophy syndrome (MFLS) or progeroid fibrillinopathy, is an extremely rare medical condition which manifests as a variety of symptoms including those usually associated with Marfan syndrome, an appearance resembling that seen in neonatal progeroid syndrome (NPS; also known as Wiedemann–Rautenstrauch syndrome), and severe partial lipodystrophy. It is a genetic condition that is caused by mutations in the "FBN1" gene, which encodes profibrillin, and affects the cleavage products of profibrillin, fibrillin-1, a fibrous structural protein, and asprosin, a glucogenic protein hormone. As of 2016, fewer than 10 cases of the condition have been reported. Lizzie Velasquez and Abby Solomon have become known publicly through the media for having the condition.

In addition to severe lipodystrophy (loss of adipose tissue), individuals with MPL show a concomitant marked loss of lean tissue mass, which also contributes to their "skinny" appearance. Based on visual inspection, it was originally thought that the lipodystrophy associated with MPL was generalized. However, it appears in fact to be partial, being confined to the face, distal extremities, and the and lateral regions of the buttocks. Normal amounts of subcutaneous fat are found in the torso over the chest and abdomen. As such, the breasts are normal in females with MPL.

Individuals with MPL have an appearance of being prematurely aged, but this is not due to actual early aging and is instead due to their paucity of subcutaneous fat. As such, MPL is not truly a form of progeria.

In 2016, it was discovered that the partial lipodystrophy associated with MPL is caused by loss of the C-terminal domain cleavage product of profibrillin and novel glucogenic protein hormone, which has been named asprosin. Due to asprosin deficiency, individuals with MPL eat less, and do not gain weight or develop symptoms of diabetes like insulin resistance. MPL patients burn less energy than normal individuals, but also consume less, and their net energy balance is moderately reduced. In contrast to MPL patients, whose asprosin is undetectable in the blood, individuals with obesity and diabetes have elevated levels of asprosin. As such, "FBN1" has been nicknamed the "thin gene", and drug development for targeted inhibition of asprosin signaling is considered to be an "unusually promising" potential therapeutic route in the treatment of obesity and diabetes.