Membranous lipodystrophy of bone

A 23-year old man with a fracture of the right lateral malleolus was found to have osteolytic lesions of the lower end of both fibulas and of the right talus. He was mentally defective from birth, with convulsions from the age of 4 years and a limp since the age of 15. Biopsy tissue from the right fibula that was removed one year after the fracture consisted of marrow adipose tissue that had been transformed by the development of thick, convuluted PAS positive membranes around the cells. Electron microscopy indicated that each membrane had a complex, microvillous substructure. At the time of biopsy, lytic lesions were found in both femoral medial condyles and, one year later, in the distal shaft of the left radius. Membranous lipodystrophy is a rare, generalized, skeletal disease that was previously reported in Finland and Japan, and is usually followed by progressive presenile dementia.     

Membranous lipodystrophy. Light and electron microscopic study of a biopsy case

Membranous lipodystrophy is a peculiar systemic disease almost exclusively found in Japan and Scandinavia and characterized by formation of numerous membranous structures in the adipose tissue of bone marrow and soft tissue. Light and electron microscopic study of a biopsy case of the disease was presented. The membranous structures consisted of membrane and inner space on both light and electron microscopic study. The membrane consisted of two kinds of layers, dense and amorphous. The dense layer was positive for lipid stainings. The amorphous layer did not show any definite lipid constituents and was supposed to consist of an amorphous substance derived from abnormal fat metabolism of diseased fat cells, degenerative cytoplasms of the diseased cells, and/or stromal cells. It probably also had some stromal substance alteration due to membranolipodystrophic change. Accumulation of the amorphous layer in the interstitium leads to degeneration and disappearance of adjacent fat cells. This process may play a role in further advance of membranous structures.     

Cartilaginous membranocystic lesions mimicking membranous lipodystrophy of bone

Two cases are presented in which membranocystic lesions were observed in the cartilaginous tissue of surgical specimens. In both cases, the histological and ultrastructural features were reviewed, and S-100 protein distribution was examined immunohistochemlcally in one case. In both cases, the membranocystic lesions were observed to be adjacent to ballooned chondrocytes. In one case, several chondrocytes showed partially membranocystic lesions in their cytoplasm. The chondrocytes and nuclei in membranocystic lesions were stained positively for S-100 protein. It is suggested that the membranocystic lesions in the cartilaginous tissue were associated with the degeneration of the chondrocytes.     

An objective lipodystrophy severity grading scale derived from the lipodystrophy case definition score

HIV lipodystrophy can be objectively diagnosed using a score derived from the 10 parameters in the HIV lipodystrophy case definition (LDCD). Lipodystrophy severity remains subjectively determined by physical examination and patient assessment. Regional dual-energy x-ray absorptiometry (DEXA) and single-slice abdominal computed tomography (CT) scanning are objective but are gender-dependent body composition measures. The LDCD score may provide a means of generating an objective and lipodystrophy grading/severity scale applicable to both men and women. Total and regional clinical lipodystrophy severity scores (generated using the HIV Outpatient Study [HOPS] scale: nil (0), mild (1), moderate (2), and severe (3) lipoatrophy or fat accumulation in 8 body regions) were correlated with objective measures of LD (LDCD score, DEXA, abdominal CT) and metabolic (lipid, glycemic, acid-base) parameters known to correlate significantly with lipodystrophy severity. Analysis was based on 417 lipodystrophic adults and 371 controls recruited to the HIV LDCD study. Correlation coefficients were used to compare physician and patient assessments (rPhysician, rPatient) with objective LD measures and metabolic parameters. The strongest objective correlate of total clinical lipodystrophy severity was the LDCD score (rPhysician = 0.641 [95% CI, 0.584-0.698]; rPatient = 0.620 [95% CI, 0.561-0.678]), whereas the strongest imaging correlate (trunk:limb fat ratio on DEXA) was significantly lower (rPhysician = 0.483 [95% CI, 0.420-0.546]; rPatient = 0.475 [95% CI, 0.412-0.538]; P < 0.001). The LDCD score also yielded significantly greater correlations with 7 of the 8 metabolic parameters than did clinical lipodystrophy severity scores. Based on quartiles of physician-rated severity, the LDCD scores were categorized to allow for rating of lipodystrophy as absent (LDCD score < 0), grade 1 (0-9.9), grade 2 (10-14.9), grade 3 (15-22.9), and grade 4 (>or=23). In conclusion, the LDCD score is the best objective measure of lipodystrophy severity and, in contrast to DEXA and CT, it is also gender independent. Subjective assessment of lipodystrophy severity could possibly be abandoned in cross-sectional studies. The LDCD score and its derived lipodystrophy grading scale merit prospective evaluation.     

Membranous fat necrosis of the breast

To investigate the pattern and prevalence of membranous fat necrosis of the breast we examined 25 breast biopsies or mastectomy specimens performed for recurrent lumps following conservative surgery and radiation therapy. In addition, we examined 41 consecutive cases taken from our files coded as fat necrosis which were associated with several aetiologies. Our results demonstrate that membranous fat necrosis of the breast occurs in association with several aetiologies but in its florid form is most often due to radiation therapy.     

Mesenteric lipodystrophy.

Three cases of mesenteric lipodystrophy with a wide range of clinicopathological features are reported. Mesenteric lipodystrophy may present as an acute abdomen or with non-specific upper abdominal symptoms. Routine biochemical and haematological investigations are within normal limits. Histological examination shows lipid-filled macrophages in sheets and bands with focal cyst formation. Mesenteric lipodystrophy is a rare condition. A firm diagnosis can be reached only by histological examination and a number of conditions need to be considered in the differential diagnosis.     

Membranous glomerulonephritis.

In a clinicopathological survey of idiopathic membranous glomerulonephritis (MGN) in 85 patients the predominance of the condition among men could be at least partly explained by an increased risk of exposure to organic solvents and heavy metals in the course of work. This may have implications for the advice given to these patients after MGN has been diagnosed. The selectivity of proteinuria could predict the likely outcome of the disease.     

Update on HIV lipodystrophy

When prescribed appropriately and taken adherently, antiretroviral therapy can consistently and durably suppress HIV replication, potentially translating into years of near normal health for HIV-infected persons. However, presently available antiretrovirals are associated with a cluster of physical and metabolic symptoms termed HIV lipodystrophy. This article reviews the state of knowledge about the pathogenesis and treatment of the various manifestations of these adverse effects.     

Ultrastructural abnormalities of the liver in total lipodystrophy

We present the results of light and electron microscopy studies of the liver in an 8-year-old girl with congenital total lipodystrophy. Liver histology revealed cirrhosis, and ultrastructural study showed mitochondrial abnormalities and an increase in the number of peroxisomes. A potential relationship between the high fatty acid concentration in the serum and the peroxisomal proliferation is considered.     

Ultrastructural abnormalities of the liver in total lipodystrophy

The morphology of the liver of a child with total lipodystrophy is presented. Prominent changes include fat deposition, aberrant mitochondrial forms, and an apparent increase in peroxisomes with aberrant morphology. (The latter lack terminal plates and instead have dense matrix granules.) Increased collagen formation is noted; a potential relationship between the increased and aberrant peroxisomes and abnormal lipid metabolism is suggested.     

Practical applications of the HIV lipodystrophy case definition

Diagnosis of HIV-associated lipodystrophy (LD) has been limited by the absence of a validated case definition and the frequent lack of objective body composition measures. An international, objective, case-control study recruited HIV-infected, adult outpatients free of active AIDS, and a case definition model for LD was developed. The relative merits and limitations of this definition as a practical tool for the long-term monitoring of a patient's LD status over the duration of clinical treatment are discussed.     

Cardiomyopathy in congenital complete lipodystrophy

Molecular genetic studies have pointed to a relationship between congenital lipodystrophy syndromes and some cardiac disorders. For instance, mutations in LMNA cause either lipodystrophy or cardiomyopathy, indicating that different mutations in the same gene can produce these clinical syndromes. The present authors describe a 10-year-old female with Berardinelli-Seip congenital complete lipodystrophy (MIM 606158) caused by homozygosity for a frameshift mutation in BSCL2. In addition to the typical attributes of complete lipodystrophy, this subject had hypertrophic cardiomyopathy diagnosed in the first year of her life; its progress has been followed with non-invasive imaging. The mechanism underlying the hypertrophic cardiomyopathy in complete lipodystrophy is unclear. It may result from a direct effect of the mutant gene or it might be secondary to the effects of hyperinsulinemia on cardiac development. The variability of the associated cardiomyopathy in patients with complete generalized lipodystrophy may be caused by differential effects of mutations in the same gene or of mutations in different genes which underlie the lipodystrophy phenotype.     

The complement abnormalities of lipodystrophy.

Investigation of the serum complement system in 25 patients with various forms of lipodystrophy showed no abnormality in three patients with total lipodystrophy; a single patient with limb lipodystrophy had evidence of activation of the classical complement pathway. However, of the 21 patients with partial lipodystrophy, 17 had low serum C3, with normal C4 and C2, concentrations, accompanied in 14 by a serum C3 splitting factor indistinguishable from nephritic factor, suggesting activation of the alternative pathway. These abnormalities occurred in 10 patients without clinically overt renal disease. Seven patients had overt nephritis; renal biopsies obtained in six showed mesangiocapillary (membranoproliferative) nephritis in all. Thus, the majority of patients with partial lipodystrophy have hypocomplementemia. Although nephritis may not invariably develop, the high rate of mesangiocapillary nephritis in these patients suggests that complement activation via the alternative pathway predisposes to the development of this form of glomerular disease.     

Membranoproliferative glomerulonephritis with partial lipodystrophy

Summary The course of disease of a patient with membranoproliferative glomerulonephritis and partial lipodystrophy is described. The case is further characterized by a deficiency of C₃ and of C₃-activator, by normal values of C₄, by evidence of the nephritogenic factor, by raised fibrin degradation products and by an unselective proteinuria.The course of the glomerulonephritis runs parallel to a pronounced susceptibility to infection (at first varicella, tonsillitis and measles, later pneumonia, meningitis, encephalitis and hepatitis).On account of a nephrotic syndrome and an initiative impairment of the renal function, a cytostatic treatment was begun, which although raising the C₃ level, did not influence the further course of the disease.As the patient has a healthy identical twin sister without lipodystrophy, who shows no reduction in C₃ and no nephritogenic factor, this case proves that these diseases are acquired and not genetically determined.Supported by the Deutsche Forschungsgemeinschaft.