DIFFERENTIAL DIAGNOSIS
There are a variety of other complex syndromes that present with lipoatrophy along with a number of other physical and systemic features (see below). A detailed discussion of these syndromes is beyond the scope of this chapter.
The excessive fat accumulation seen in patients with FPLD2 and HIV/ART-associated lipodystrophy could be confused with Cushing syndrome and obesity. Acromegaly can have overlapping features with generalized lipodystrophy.
In an infant with generalized lipodystrophy, the following conditions should also be considered:
●Leprechaunism (Donohue syndrome) is included in some lipodystrophy classifications, as the patients present with generalized lipodystrophy, severe insulin resistance, acanthosis nigricans, and hirsutism. In contrast to CGL, these patients have a distinct elfin facies, severe intrauterine growth retardation, prominent nipples, cutis laxa, mutations in the insulin receptor gene, and death during infancy.
●SHORT syndrome (short stature, hyperextensible joints or hernia, ocular depression, Rieger anomaly [iridocorneal mesodermal dysgenesis], and teething delay) is also included in some lipodystrophy classifications, as there is congenital lipoatrophy of the face and upper body. This condition is distinguished by the aboveoutlined abnormalities, intrauterine growth retardation, delayed bone age, mutations in PIK3R1, and a dysmorphic facies, which includes a triangular shape, micrognathia, deep-set eyes, and anteverted ears. Metabolic abnormalities are rare to absent.
●Progeria-type syndromes are characterized by limb lipoatrophy, cardiovascular disease and diabetes, but they are accompanied by muscle wasting, sclerodermatous changes, cataracts, and other signs of premature aging. Some of the progeric syndromes have LMNA mutations similar to those associated with FPLD, and may be considered as part of a broader group of disorders termed laminopathies (see Table 63.10).
●In Cockayne syndrome, lipoatrophic changes are accompanied by growth delay, retinal abnormalities, photosensitivity, and defects in DNA repair (see Chs. 63 & 87).
●AREDYLD syndrome: congenital generalized lipoatrophic diabetes is associated with an acrorenal field defect and ectodermal dysplasia. In the case of partial lipodystrophy, there was a report of diffuse, symmetrical lipoatrophy of the lower extremities following extensive inflammation due to lobular panniculitis. Neither underlying autoimmune diseases nor exogenous causes were identified.
Localized lipodystrophies should be differentiated from initial phases of progressive lipodystrophy, morphea, lupus panniculitis, and atrophoderma of Pasini and Pierini. Although there is overlap amongst the various types of localized lipodystrophy, the distribution and morphology combined with a history of injections, the presence clinically or histologically of panniculitis, and associated autoimmune disorders may aid in the diagnosis.
Poland syndrome is a rare congenital disorder consisting of unilateral partial or total absence of a breast and/or pectoralis major muscle plus ipsilateral symbrachydactyly, which may simulate lipoatrophy. Lipohypoplasia, as is seen in disorders such as Proteus syndrome, can also mimic lipoatrophy.
Lastly, whole-body MRI has been shown to assist in differentiating the various subtypes of lipodystrophies, based upon the amount and extent of residual adipose tissue and the absence or preservation of marrow fat. This information, in combination with the clinical phenotype and especially genetic testing, improves diagnostic accuracy and prognostication.