The patient was a thirty-nine-year-old woman who manifested pain and tenderness in both knees since the age of thirty-three. A routinary laboratory analysis in another centre demonstrated type IV hyperlipidemia. She did not refer any other clinical symptoms. She had no history of suffering fractures.
The patient was a thirty-nine-year-old woman who manifested pain and tenderness in both knees since the age of thirty-three. A routinary laboratory analysis in another centre demonstrated type IV hyperlipidemia. She did not refer any other clinical symptoms. She had no history of suffering fractures. On admission, results of physical exam were normal showing movement of all extremities without any inflammatory signs, as increase in warmth or edema. Laboratory data demonstrated hypercalciuria of 841 mg/d and hyperphosphaturia of 1824 mg/d with serum calcium level and serum phosphorus concentration within normal limits. Lipid plasma levels were trygliceride concentration 525 mgr/dl, plasma total-cholesterol 204 mgr/dl and high-density lipoprotein-cholesterol (HDL-C) 24 mgr/dl. Lypidogram revealed beta 28.5%, prebeta 66.5% and alpha 5.0%. The rest of laboratory data did not show other significant findings. In the moment of her visit to hospital she only manifested pain in both knees without revealing neurological nor psychiatric symptoms. The younger brother of the patient suffers a non-drafted bone disease. Plain radiographs of knees were obtained. The study was completed with radiographs of hands, ankles, cranium and spinal column. Biopsy from the cystic lesions of the affected bone marrow was performed to obtain histopathological and radiological correlation.
Membranous lipodystrophy represents a rare disease manifested as progressive skeletal and neuropsychiatric symptoms. In the description of an autopsy case with unusual findings in the nervous and skeletal systems Nasu et al firstly named the term "membranous lipodystrophy" [1]. Similar findings were reported in Finland by Hakola, referred as "progressive dementia and lipomembranous polycystic osteodysplasia". The aetiology of this disease is unknown. Some hypotheses have been proposed such as a development anomaly of blood vessels of bone, a metabolic disorder affecting structural common to both bones and myelin sheaths (Sourander et al. 1981), abnormal lipid metabolism, neuroaxonal dystrophy [Amano et al. 1987] and disturbance of glycolipid or glycoprotein metabolism [2]. Hereditary factors are also suggested. The clinical signs and symptoms may be divided into three groups: skeletal, psychiatric and neurological [3]. Although patients refer tenderness and local pain in the joints as the most common skeletal symptoms, pathological fractures of long bones may be the main cause of their visit to hospital. Radiological exams reveal large symmetric transparent cyst-like lesions in the metaphyses of long bones, in metatarsal bones and in phalanxes. The ribs, cranium, pelvic bones and spinal column are rarely affected [4]. The cortex near the affected region may seem thin in some cases but periosteal reaction is quite infrequent. Some patients may reveal psychiatric symptoms as the initial clinical feature manifested as presenile dementia or as upheavals of the mood. The neurological symptoms consist of convulsions, ataxia, urinary incontinence and disturbance of consciousness and appear in the final stages of the disease. Some authors have also reported that peripheral neuropathy may be one of the cardinal features of membranous lipodystrophy. The diagnosis of membranous lipodystrophy should be based on three main features: clinical manifestations, radiological exams and histopathological findings. Characteristic patterns of the illness involve the peculiar membranous transformation of marrow adipose tissue of the bone and, are not seen in hemangioma or lipoma of bone, healing fractures, or traumatic fat necrosis [5]. Other adipose tissues throughout the body are also affected. The presence of neuropsychiatric manifestations allows differentiating membranous lipodystrophy from other similar diseases.
Membranous lipodistrophy.
Based on the provided X-ray images of the knees, hands, ankles, as well as the skull and spine, the following main characteristics can be observed:
1) Both knee joints: The distal femur and proximal tibia show multiple, relatively symmetrical radiolucent areas (resembling cystic or cyst-like lesions), with localized cortical thinning.
2) Hands: Multiple round or oval radiolucent areas near the proximal and distal joints of the phalanges, with relatively clear boundaries and obvious cystic changes; no evident fracture lines or severe bone destruction are observed.
3) Ankles: Similar multiple radiolucent or cystic areas can be seen in the distal tibia and fibula, with relatively thin cortical bone, and no obvious disruption of bone trabeculae or collapse.
4) Skull and spine: The skull exhibits scattered regions of decreased density with diffuse borders; on the anteroposterior and lateral spine images, the vertebral bodies show no obvious collapse or deformity, though there is slightly reduced bone density in some areas.
Based on the radiological findings and the patient’s medical history (e.g., secondary hyperlipidemia, persistent bilateral knee pain, symmetrical cystic bone lesions, etc.), the following diagnoses and differential diagnoses are considered:
(1) Membranous Lipodystrophy (Nasu-Hakola Disease): Also known as “lipomembranous polycystic osteodysplasia,” it can present with multiple bone cysts, neurological and psychiatric symptoms, and is often associated with abnormal lipid metabolism. Radiologically, it is characterized by multiple cystic radiolucent lesions in both long bones and small bones, symmetrically distributed, frequently involving the bones of the extremities.
(2) Metabolic Bone Disease (e.g., brown tumors caused by hyperparathyroidism): Although such conditions can also present with bone cysts and osteoporosis, they are often accompanied by abnormalities in serum calcium, phosphorus, and related indicators; moreover, the pattern of distribution may not fully match this case.
(3) Giant Cell Tumor of Bone or Simple Bone Cyst: These typically manifest as localized, eccentric lesions, often in a single bone or a small number of bones, and they do not commonly present in multiple, highly symmetrical patterns as seen in this case.
(4) Fibrous Dysplasia: Often shows expansile bone changes with irregular borders, and can cause significant thinning or destruction of the cortex, which differs from the imaging findings in this case.
Considering the patient's age (39 years), history of long-term bilateral knee pain, multiple and symmetrically distributed cystic bone lesions on imaging, laboratory findings indicating hyperlipidemia (Type IV), as well as references to Nasu-Hakola disease (membranous lipodystrophy) in the literature, the most likely current diagnosis is:
Membranous Lipodystrophy (Nasu-Hakola Disease).
Since this disease is relatively rare and a definitive diagnosis often requires additional pathological and genetic testing, a biopsy of the bone lesion or relevant genetic tests may be conducted when necessary to confirm the diagnosis.
(1) Treatment Strategies:
• Conservative Treatment: For joint pain, non-steroidal anti-inflammatory drugs (NSAIDs) or appropriate analgesics can be used, along with nutritional support. Control hyperlipidemia and, if necessary, use lipid-lowering medications under the guidance of an endocrinologist or metabolic specialist.
• Surgical Treatment: For large cystic lesions that compromise bone stability or pose a high risk of fracture, prophylactic internal fixation or curettage and bone grafting can be considered. If a pathological fracture occurs, prompt surgical intervention is required to ensure stability.
(2) Rehabilitation and Exercise Prescription:
• Early Phase (Recovery and Protection): Focus on maintaining joint function with low-intensity, low-load exercises. Non-weight-bearing exercises can be performed, such as limb stretches in seated or supine positions. Deep squats or weight-bearing squats and other high-stress activities should be avoided. Exercises may be done 3-4 times per week, approximately 20 minutes per session, keeping the intensity at a level that does not exacerbate pain.
• Intermediate Phase (Muscle Strengthening): Once the condition is relatively stable, gradually add light resistance training, such as elastic band exercises or small-range resistance drills (e.g., light dumbbells or water exercises). The intensity should be increased gradually without causing significant joint pain or fatigue. It is recommended 3-5 times per week, about 30 minutes per session, keeping the heart rate around 50%-60% of the maximum heart rate.
• Late Phase (Functional Consolidation): If bone strength has improved and there is no increased risk of fractures, progressively strengthen the lower limbs and core stability. Incorporate balance exercises (e.g., standing balance, single-leg stance with eyes closed) when safe, to improve joint stability. Exercise frequency can be maintained at 3-5 times per week, 30-45 minutes per session. If needed, bone density or joint status can be evaluated every 2-4 weeks.
• Special Precautions: Because of the fragile bone structure and potential involvement of the central nervous system in this condition, it is crucial to avoid excessive impact or high-risk movements. Increase exercise volume gradually and closely monitor joint pain and overall health. If there is any marked increase in pain or suspected fracture risk, seek medical advice immediately and reassess.
Disclaimer: This report is based on the available imaging and clinical data for reference only. It does not replace an in-person consultation or professional medical advice. Specific diagnosis and treatment plans should be determined by taking into account the patient’s actual situation and professional medical evaluation.
Membranous lipodistrophy.
