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PubMed This is a summary of 5 peer-reviewed journal articles Updated
Endocrinology · Familial Partial Lipodystrophy Type 6 (LIPE-Related)

Physical Symptoms and Systemic Signs of LIPE-Related FPLD

At a Glance

LIPE-related FPLD6 typically causes fat loss in the lower legs with fat accumulation in the face, neck, armpits, and abdomen. Some people also report muscle weakness, retinal deposits, nerve symptoms, or kidney injury, but genetic testing is needed for diagnosis.

While many forms of lipodystrophy focus on what is happening inside the body, LIPE-related Familial Partial Lipodystrophy (FPLD6) is often first suspected by the unique way it reshapes the body’s physical frame. Because this condition involves a mutation in the LIPE gene—which helps your body break down and move fat—the fat accumulates in an atypical pattern [1][2].

Understanding these physical markers is essential because they often serve as the “clues” that raise clinical suspicion, though genetic testing and expert clinical assessment are required for a diagnosis.

The Signature Fat Distribution Pattern

In FPLD6, your body loses the protective layer of fat just under the skin (subcutaneous fat) in some areas while gaining ectopic fat in others [1]. This often begins in early adulthood, though the exact timing can vary [1][3].

  • Lipoatrophy (Fat Loss): The most striking feature is the loss of fat in the lower limbs [1]. Your legs may appear very lean or “muscular” because the fat that usually smooths over the muscles is gone [2].
  • Fat Accumulation: As fat storage capacity is reduced in the legs, ectopic fat often accumulates in the upper body. You may notice increased fat in the:
    • Face and Neck: Unlike some other forms of lipodystrophy that cause a “sunken” facial appearance, FPLD6 often causes fat to build up in the face and neck [1][2].
    • Axillary (Armpits): Unusual fatty deposits may appear in or around the armpits [1].
    • Abdomen: “Central” weight gain in the stomach area is common, even if your limbs are very thin [2][3].

In some cases, these deposits can look pseudo-lipomatous, meaning they resemble soft, fatty lumps known as lipomas. This is why FPLD6 is frequently confused with Multiple Symmetric Lipomatosis (MSL), a condition where large fatty masses grow around the neck and shoulders [1][3].

Systemic and “Extra-Metabolic” Reports

FPLD6 is unique because the LIPE gene affects more than just fat. While the following findings are variable and not established routine manifestations in every affected person, they have been reported in some individuals:

  • Muscle Weakness (Myopathy): Some patients have been reported to develop distal symmetric myopathy, which is a progressive weakness in the muscles furthest from the center of the body, such as the hands and feet [2][1]. Doctors may find an elevated level of creatine kinase (CK)—a marker of muscle breakdown—in your blood [2].
  • Retinal Changes: Research has identified small, yellow-white deposits called drusen-like deposits in the back of the eye (the retina) in some patients [1][3]. If you have diabetes, standard diabetic retinopathy screening is also important.
  • Nerve and Kidney Involvement: In rare reports, patients have experienced peripheral nerve damage (which can cause tingling or numbness) and renal tubular injury (a specific type of kidney damage) [3]. Screening for these is symptom- and specialist-directed.

Comparing FPLD6 to Other Subtypes

It can be helpful to know how your physical appearance might compare to other types of partial lipodystrophy your doctor may have seen before.

Feature LIPE-Related (FPLD6) Dunnigan Type (FPLD2)
Face/Neck Often gains fat; can look full or rounded [1]. Can also include fat accumulation in the face, neck, and visceral abdomen, making phenotypic overlap common [4].
Legs Significant fat loss [2]. Significant fat loss [5].
Unique Signs Muscle weakness and retinal deposits reported in some patients [1][3]. Generally lacks these specific muscle and eye findings [5].

If you have noticed these physical changes, it is important to share these specific observations with your care team, as they can raise clinical suspicion for the LIPE genetic variant [1].

Common questions in this guide

What does LIPE-related FPLD6 usually look like physically?
LIPE-related FPLD6 often causes loss of the fat layer in the lower legs, making them look unusually lean or muscular. Fat may build up in the face, neck, armpits, and abdomen, and these changes often begin in early adulthood, although timing varies. This pattern can suggest the condition but does not confirm it.
Can FPLD6 cause weakness in the hands or feet?
Some people with LIPE-related FPLD6 have reported weakness in muscles farther from the center of the body, such as those in the hands and feet. A clinician may consider a blood creatine kinase test when symptoms suggest muscle involvement, but muscle findings are not present in everyone.
Does LIPE-related FPLD6 affect the eyes, nerves, or kidneys?
Some affected people have been reported to have drusen-like deposits in the retina, tingling or numbness from peripheral nerve involvement, or kidney tubular injury. These findings are variable, so eye, nerve, and kidney evaluations are generally guided by symptoms and a specialist; people with diabetes should continue standard diabetic retinopathy screening.
How can FPLD6 be distinguished from FPLD2 or multiple symmetric lipomatosis?
FPLD6 and Dunnigan-type FPLD2 can both cause fat loss in the legs with fat accumulation in the face, neck, or abdomen, so their appearance may overlap. Fat deposits in FPLD6 can resemble lipomas and multiple symmetric lipomatosis, while muscle weakness and retinal deposits have been reported in FPLD6 but are generally not described in FPLD2. Clinical assessment and genetic testing are needed to clarify the diagnosis.
What confirms a diagnosis of LIPE-related FPLD6?
The physical pattern can raise suspicion, but it cannot confirm LIPE-related FPLD6 on its own. Diagnosis requires expert clinical assessment and genetic testing to look for a disease-causing LIPE variant. Your care team can choose appropriate testing based on your examination and clinical history.
When should someone with FPLD6 be screened for kidney, nerve, or eye problems?
Screening for nerve or kidney involvement is usually considered when symptoms or a specialist’s assessment suggest it, because these findings have been reported only in some people. If you have diabetes, routine diabetic retinopathy screening remains important, and an ophthalmologist can advise whether additional eye evaluation is appropriate.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my physical exam, do my fat accumulation patterns look more like 'pseudo-lipomatous' deposits or actual masses similar to multiple symmetric lipomatosis?
  2. 2.Given that LIPE-related FPLD can involve the muscles in some patients, should we check my creatine kinase (CK) levels based on my symptoms?
  3. 3.Can you refer me to an ophthalmologist to screen for retinal changes, or just for standard diabetic retinopathy screening?
  4. 4.How does the fat distribution in my face and neck fit with other types of partial lipodystrophy like FPLD2?
  5. 5.Should we perform specific tests to screen for the renal tubular or nerve issues reported in other LIPE cases, or only if I have symptoms?

Questions For You

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References

References (5)
  1. 1

    LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells.

    Sollier C, Capel E, Aguilhon C, et al.

    European journal of endocrinology 2021; (184(1)):155-168.

    PMID: 33112291
  2. 2

    Homozygous LIPE mutation in siblings with multiple symmetric lipomatosis, partial lipodystrophy, and myopathy.

    Zolotov S, Xing C, Mahamid R, et al.

    American journal of medical genetics. Part A 2017; (173(1)):190-194 doi:10.1002/ajmg.a.37880.

    PMID: 27862896
  3. 3

    Case report: First Chinese patient with family partial lipodystrophy type 6 due to novel compound heterozygous mutations in the LIPE gene.

    Zhou Y, Zhang L, Ding Y, Zhai Y

    Frontiers in genetics 2024; (15()):1417613 doi:10.3389/fgene.2024.1417613.

    PMID: 39113684
  4. 4

    Severe loss of adipose tissue in a Vietnamese lipodystrophy patient caused by LMNA p.G465D mutation: a first clinical characterization and two-year follow-up.

    Vu NP, Tran HT, Vu NB, et al.

    Journal of pediatric endocrinology & metabolism : JPEM 2022; (35(9)):1206-1210 doi:10.1515/jpem-2022-0208.

    PMID: 35822709
  5. 5

    Clinical Spectrum of LMNA-Associated Type 2 Familial Partial Lipodystrophy: A Systematic Review.

    Fernandez-Pombo A, Diaz-Lopez EJ, Castro AI, et al.

    Cells 2023; (12(5)) doi:10.3390/cells12050725.

    PMID: 36899861

This page is for informational purposes only and does not constitute medical advice. It describes reported LIPE-related FPLD6 findings; diagnosis and decisions about muscle, eye, nerve, or kidney screening should be made with your healthcare team.

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