Acquired partial lipodystrophy (ORPHA:79087)
A rare acquired lipodystrophy characterized by bilateral, symmetrical lipoatrophy of the upper body (face, neck, arms, thorax and sometimes upper abdomen) with sparing of the lower extremities and cephalothoracic progression. The disease may be associated with low serum levels of C3 and presence of C3-nephritic factor.
Epidemiology
The prevalence in Europe is less than 1/100 000. There is a female predominance with a female-to-male ratio of 4:1.
Clinical description
Onset typically occurs during childhood or adolescence but may occur as late as the fourth or fifth decade of life. Lipoatrophy is slowly progressive, starts on the face and then extends downwards to the neck, shoulders, upper limbs and/or thorax. The hips, thighs, distal legs and gluteal regions are initially normal, however, lipohypertrophy may present post-puberty, especially in females. Mesangiocapillary glomerulonephritis is reported in one third of patients and is associated with low complement-component 3 (C3) serum levels and the presence of C3-nephritic factor. Whilst there is an increased risk of insulin resistance and metabolic complications (including menstrual irregularities, hirsutism, diabetes mellitus, dyslipidemia, hypertension and hepatic steatosis), these are less frequently observed compared to other types of lipodystrophies. Occasionally, functional anomalies including sensorineural deafness, epilepsy, intellectual deficit, myopathy and retinal changes may be associated.
Etiology
Whilst the etiology is unknown, susceptibility has been linked to heterozygous mutations in the LMNB2 (19p12.3) gene, encoding the lamin B2 nuclear envelope protein. Nevertheless, this mutation is very inconstant. Moreover, the frequently early occurrence of the disease suggests yet unknown genetic causes, perhaps involved in the innate immunity.
Diagnostic methods
Diagnosis is essentially based on the characteristic subcutaneous fat loss pattern. Physical examination (including skin fold thickness measurements) and MRI studies are important to assess fat loss distribution. Measurement of serum complements and autoantibodies (low C3 and presence of C3-nephritic factor), absence of family history of lipodystrophy, an onset during childhood/adolescence, and biopsy may support diagnosis. Clinical judgement should be used for screening for co-morbidities.
Differential diagnosis
Differential diagnosis includes anorexia nervosa, cachexia, starvation, diencephalic syndrome, multiple symmetric lipomatosis and other rare progeroid syndromes and disorders affecting growth and development. In addition, other forms of acquired lipodystrophy observed may be associated with a broad spectrum of autoimmune diseases, including systemic lupus erythematosus, juvenile dermatomyositis, celiac disease, or pernicious anemia and vasculitis.
Management and treatment
Surgical management of the lipodystrophy is feasible, and is mainly aimed at aesthetic improvement. Treatment of the metabolic manifestations, if present, should follow the same guidelines as those used for other forms of insulin resistance: physical exercise, insulin-sensitizing medication (metformin or, if available, glitazones), agonists of GLP1 receptor, and finally insulin (or preferably insulin analogues)) and management of the hypertension and hypertriglyceridemia. Nephrological follow-up should also be recommended. Metreleptin, indication authorized in Europe, may be considered for hypoleptinemic patients with severe metabolic derangements, where other treatments have failed to achieve adequate metabolic control.
Prognosis
The prognosis is largely unknown but greatly depends on the extent of the nephropathy, which may progress to renal insufficiency.

                            Last update: 
                            October 2019


                            - Expert reviewer(s): 
                            Pr Marie-Christine VANTYGHEM