[Glomerular lipidosis]. / Lipidosi glomerulari.

Lipidoses occur for an abnormal storage parenchymal deposition of lipids and products of their metabolism in large amounts or sometimes, involving only some particular tissue structures. The lipid storage is usually due to an inborn error causing an enzyme absence /deficiency in the primary lipidoses and to a complex metabolism alterations in the secondary forms. However, histologically all lipid depositions look very similar, and immunohistochemical investigation, clinical pictures knowledge and genetic tests need to make a correct diagnosis. Lipid deposition causes parenchymal structural changes especially of glomeruli resulting in renal function impairment and proteinuria and haematuria appearance. This manuscript gathers clinical and histological features present in these storage pathologies. Renal involvement is described in Anderson-Fabry disease, in hyperlipoproteinemias, in lecithin-cholesterol acyltransferase deficiency, in Gaucher disease and finally in secondary lipidoses features such as nephrotic syndrome, Alagille disease, and toxic or ischemic renal damage. Recently the replacement enzymatic therapy availability is substantially modifying the clinical picture and the outcome in some lipidoses such as Anderson-Fabry and Gaucher diseases. Therefore, it is import to be aware of these disorders, not only for making a correct diagnosis but also for starting, when it is possible, an effective therapy.

Diagnosis and management of lipoedema in the community.

Lipoedema is a chronic progressive adipose disorder that affects mainly women and presents as symmetrical enlargement of the buttocks and legs. It is commonly misdiagnosed as obesity or lymphoedema, but careful assessment will reveal a disproportionate enlargement below the waist which is resistant to dieting, sparing of the feet, legs are tender or painful to touch and bruise easily, there is occasional orthostatic oedema, and there is often significant psychological morbidity. Lipoedema is a oestrogen-regulated condition with onset around puberty in 78% of women, and there is often a strong family history. The condition is exacerbated by weight gain and there is increasing anecdotal evidence that women who are obese are seeking a diagnosis of lipoedema, either to procure NHS funded manual lymphatic drainage, or to medicalise their obesity and avoid acknowledging that the responsibility for their weight gain is lifestyle orientated. Management of lipoedema consists of accurate diagnosis, psychological care, management of orthostatic oedema, and prevention of progression through skin care and weight management.

Living with lipoedema: reviewing different self-management techniques.

At present, there is no proven cure for lipoedema. Nevertheless, much can be done to help improve symptoms and prevent progression. Many of these improvements can be achieved by patients using self-management techniques. This article describes the range of self-management techniques that community nurses can discuss with patients, including healthy eating, low-impact exercise, compression garments, self-lymphatic drainage, and counselling.

Early lipoedema diagnosis and the RCGP e-learning course.

Frequently misdiagnosed as obesity, lipoedema is chronic condition involving an abnormal build-up of fat cells in the legs, thighs and buttocks that cannot be shifted by exercise or dieting. Estimated to affect up to 11% of the female population, the condition is widely unknown by health professionals. This means women typically wait for many years before diagnosis. This allows the condition to progress unchecked, resulting in unnecessary deterioration and the development of associated comorbidities, as well as significant pain and mental anguish. A free, 30-minute Royal College of General Practitioners (RCGP) e-learning course created in partnership with Lipoedema UK aims to rectify this situation by educating nurses, GPs and other health professionals on how to diagnose and manage lipoedema in primary care. This article aims to describe the condition of lipoedema, how to recognise/diagnose it, current treatment options and the findings of a 240-patient survey carried out by Lipoedema UK in 2013 that included documenting the difficulties for patients in obtaining a diagnosis as well as the mental and physical effects of the condition.

[Experience of the conservative treatment of the gallbladder cholesterosis in children].

Gallbladder cholesterosis (GBC) was described more than 150 years ago, but so far the disease remains unknown. With respect to children's age appear solitary works. The introduction of modern pediatric practice of the intrascopic research methods enabled us to objectively identify the pathological changes in the gallbladder wall. Many years of experience studying gallstone disease has shown that almost a third of children cholelithiasis combined with gallbladder cholesterosis. However, until cholecystectomy the last one was diagnosed in only 10% of children. Meanwhile, our experience in children observing with GBC showed that conservative therapy effective in childhood. The aim of this study was to demonstrate the clinical example of the possibility of conservative treatment of gallbladder cholesterosis in children.

Lipoedema: presentation and management.

Lipoedema is a distinct clinical condition characterized by bilateral, symmetrical enlargement of the buttocks and lower limbs owing to excess deposition of subcutaneous fat. It is found almost exclusively in women. The common features associated with this condition are 'column- shaped' legs with sparing of the feet, bruising, sensitivity to pressure, and orthostatic oedema. The progression to lipo-lymphoedema or morbid obesity is possible. Conservative measures used in the management of lymphoedema can prevent progression/limit the orthostatic oedema. Surgical procedures may also play a part in the management of lipoedema.

Lipidomics in diagnosis of lipidoses.

A review is presented of the major clinical features of a number of glycolipidoses including Fabry, Gaucher, Tay-Sachs, metachromatic leukodystrophy as well as CeroidLipofucinosis and Sjogren-Larsson syndrome. The possibilities offered by lipidomics for diagnosis and follow-up after enzyme replacement therapy are presented from a practical perspective. The contribution of HPLC coupled with tandem mass spectrometry has considerably simplified the detection and assay of abnormal metabolites. Corresponding internal standards consisting of weighed mixtures of the stable-isotope labeled metabolites required to calibrate and quantitate lipid components of these orphan diseases standards have yet to become commercially available. A lipidomics approach has been found to compare favorably with DNA-sequence analysis for the rapid diagnosis of pre-birth syndromes resulting from these multiple gene defects. The method also seems to be suitable for screening applications in terms of a high throughput combined with a low rate of false diagnoses based on the wide differences in metabolite concentrations found in affected patients as compared with normal subjects. The practical advantages of handling samples for lipidomic diagnoses as compared to enzyme assay are presented for application to diagnosis during pregnancy.

Feline hepatic lipidosis.

Hepatic lipidosis occurs when lipid mobilized to the liver exceeds lipid leaving the liver via formation of very-low-density lipoproteins or by oxidation. Hepatic lipidosis in cats is associated with overt liver dysfunction. In affected cats, excess lipid is mobilized to the liver because of starvation. Removal of hepatic lipid may be impaired because of protein malnutrition, a relative carnitine deficiency, or oxidative damage to peroxisomes and other hepatic organelles. Hepatic lipidosis occurs in adult cats, and is manifest by signs of weight loss, depression, vomiting, and icterus. Diagnosis is achieved by evaluating laboratory and diagnostic imaging data, in conjunction with a liver biopsy. Aggressive tube feeding is the treatment of choice. With this treatment, survival rates are 60% to 80%.

Hyperlipidemia, hyperlipemia, and hepatic lipidosis in American miniature horses: 23 cases (1990-1994).

The medical records of 23 American Miniature Horses with hyperlipidemia, hyperlipemia, or hepatic lipidosis were reviewed. The most common clinical signs were anorexia and lethargy. The mean duration of clinical signs was 2.4 days. A primary disease was identified in 19 cases. Enterocolitis was the most common primary disease (n = 10). Intentional feed restriction, as part of treatment for colic, resulted in hyperlipemia in 2 horses and hyperlipidemia in 1. Four horses had primary hyperlipemia, 3 of which had signs of hepatoencephalopathy secondary to hepatic lipidosis. Dextrose, heparin, and insulin were the most common treatments. The overall survival was 61% (14/23). All horses with peak serum triglyceride concentrations > 1,200 mg/dl died or were euthanatized, whereas all but 1 with peak serum triglyceride concentrations < 1,200 mg/dl survived. These findings suggest that when American Miniature Horses, like other ponies and donkeys, are in a negative energy balance, they can rapidly develop hyperlipidemia or hyperlipemia. Early detection and treatment may improve survival.

Feline idiopathic hepatic lipidosis.

Feline IHL is a severe hepatopathy that can be treated by aggressive nutritional support. Until the underlying mechanisms of protein and lipid metabolism are understood in both healthy and ill cats, dietary therapy remains supportive. It is likely that the pathogenesis of IHL in cats is multifactorial, involving both increased fatty acid mobilization to the liver and a defect in oxidation of fatty acids or removal of VLDL. It is also possible that individual variation may play a role in the development of this disease in cats undergoing starvation. Continued studies will focus on the unique pathways of hepatic metabolism in the cat, and how these pathways are altered, leading to hepatic lipid accumulation and clinical disease. Hopefully, these studies can be applied to the prevention or treatment of IHL in cats.

Effects of plasmapheresis on familial type III hyperlipoproteinemia associated with glomerular lipidosis, nephrotic syndrome and diabetes mellitus.

A 59-year-old woman, one of 5 cases with familial type III hyperlipoproteinemia reported at our clinic to date, had nephrotic syndrome and diabetes mellitus, but had neither coronary atherosclerosis nor xanthoma. A renal biopsy specimen revealed a massive cluster of foam cells containing apolipoprotein B and E in the mesangial region of the kidney. A restricted diet intake combined with lipid-lowering drugs such as cholestyramine, clinofibrate, and bezafibrate, in addition to methylprednisolone was not very effective in lowering serum triglyceride and cholesterol levels within physiological ranges. Therefore, plasmapheresis, using a dextran sulfate-cellulose column, was performed. Repeated plasmapheresis resulted in a marked decrease in both serum total cholesterol and triglyceride. A second renal biopsy specimen performed 2 years later revealed a marked reduction in foam cells with concurrent improvement in her nephrotic syndrome and glucose intolerance. These results suggest that familial type III hyperlipoproteinemia may be responsible for glomerular lipidosis resulting in nephrotic syndrome. They also indicate that plasmapheresis using a dextran sulfate-cellulose column is very effective in the removal of abnormal lipoproteins such as beta-very low density lipoprotein and intermediate density lipoprotein in a case of familial type III hyperlipoproteinemia.

Treatment of idiopathic hepatic lipidosis in cats: 11 cases (1986-1987).

Idiopathic hepatic lipidosis was diagnosed in 11 cats. Cats were treated by delivery of balanced nutrients supplemented with L-carnitine via a surgically placed gastrostomy tube. Feeding through the gastrostomy tube was initiated in the hospital and was continued at home in all cats. The mean duration of gastrostomy tube feeding was 48 days (range, 22 to 98 days). Vomiting associated with feeding (3 cats) and localized cellulitis at the gastrostomy site (2 cats) were the most frequent complications. Vomiting was controlled by reducing the volume of food administered at each feeding or by administration of metoclopramide. Cellulitis was treated successfully by parenteral administration of antibiotics and local wound cleansing. Seven of 11 cats (65%) survived and have remained clinically healthy for 15 to 29 months (mean, 20 months) since diagnosis. The other 4 cats died of peritonitis (n = 1), pneumonia (n = 1), hepatic encephalopathy (n = 1), or cardiopulmonary arrest (n = 1) between 0 and 10 days after surgery.

Diagnosis and treatment of typical and atypical forms of lipopigment storage disorders.

Lipopigment storage disorders are common lysosomal diseases of unknown etiology. Four classic types have been delineated on a clinical basis, focused on the age of onset, visual and retinal impairment, epilepsy and progressive loss of mental and motor abilities. Lipopigments with ultrastructural characteristics distinct from lipofuscin accumulate mostly in the nerve cells but in many other cell types as well. Excess dolichol can be demonstrated in tissues and urine, but no primary accumulating substrate has been identified. Many cases with atypical features or course cannot be currently classified. Medical treatment includes, in all types, prevention of aspiration pneumonia with fundoplication and gastrostomy and avoidance of carbamazepine. In Spielmeyer-Vogt, Vitamin E and appropriate mental and physical stimulation improve the patient's quality of life.

Lipid storage myopathies. A review of metabolic defect and of treatment.

Various cases of lipid storage myopathies have been described. The biochemical defect could be determined in only some of these cases. The syndromes identified to date are as follows: carnitine deficiency (type I lipid storage myopathy), carnitine-palmityltransferase (CPT) deficiency and pyruvate-decarboxylase deficiency. In the last two diseases the vacuolization in muscle is not marked. The case of a 10 year old carnitine deficient patient with a history of insidious muscle weakness in the proximal limb and neck muscles is presented. The patient was treated with oral carnitine and a medium chain triglyceride diet for 18 months and her clinical status has remained improved. In other lipid storage patients prednisone treatment resulted in improvement. In cases of suspected lipid storage myopathy the following studies are indicated: 1) examination of ketone bodies in serum and urine during fasting, long chain and medium chain triglyceride diets; 2) serum triglyceride and serum carnitine; 3) study on fresh muscle and fibroblasts with labeled substrates, biochemical determination of carnitine and CPT in muscle.

Experimental enzyme replacement in genetic and other disorders.

To correct a genetic defect, it would not be enough, say, to inject the missing enzyme, since the body's immune defenses would rapidly destroy it. A "Trojan horse" is needed to evade immune surveillance. The evolution of such an approach is described, as well as how it has been used to "cure" Tay-Sachs disease in culture, utilizing immunoglobulin-disguised liposomes to bring hexosaminidase A to deficient cells.