Dermatologic Manifestations of Generalized Lipodystrophy Clinical Presentation

Two forms of generalized lipodystrophy exist, congenital and acquired, which have different clinical features.

Congenital generalized lipodystrophy

The diagnosis of generalized lipodystrophy often is obvious from birth because of the extraordinary lack of subcutaneous fat. Fat cells are present but are reduced in number and size and contain little fat. Anabolic features are observed at birth, with enlarged visceral organs. Toddlers may have a potentially dangerous hyperplasia of pharyngeal tonsils and adenoids. Lipodystrophy produces a distinctive facies.

A well-defined musculature with prominent superficial veins is one of the earliest manifestations.

Clitoral or penile hypertrophy has been evident at birth, but genitomegaly is not apparent after puberty.

The earliest skin manifestations include AN, eruptive xanthomas, hirsutism, and thick, tightly curled scalp hair that extends nearly to the eyebrows. Hirsutism of the face, neck arms, and legs may be observed at birth in some patients and tends to increase. No special growth of the pubic or axillary hair occurs.

All patients with Lawrence-Seip syndrome and lipodystrophy have AN to some degree. AN can diminish and disappear with puberty and is said to be prominent on the elbows, knees, and waist, as well as the more typical sites of the neck and axillae.

Acromegalic gigantism with advanced bone age and advanced dentition is an early and constant feature. The growth rate is most marked in the first 4 years, and these children may attain more than 90% of their adult growth within the first 10 years of life. Growth subsequently slows, and normal or short stature as adults usually is observed. Lipoatrophy does not affect female breast development at puberty, although females with this congenital lipodystrophy syndrome have a masculine habitus with marked muscularity.

Liver disease with fatty metamorphosis and cirrhosis is another constant feature, and hepatosplenomegaly tends to produce a markedly protuberant abdomen.

Childhood death due to massive GI bleeding has been reported frequently.

Diabetes mellitus usually begins in the teenage years. The diabetes is insulin resistant, and despite poor control of the diabetes, ketosis tends to be absent. Hyperlipemia usually precedes the diabetes.

An increased basal metabolic rate is a frequent finding.

Dilatation of the cerebral ventricular system has been described in most patients with generalized lipodystrophy. Intelligence may range from normal to subnormal.

Kidneys may be enlarged without apparent histologic cause, and renal failure may ensue.

Cardiomegaly frequently is observed with muscle hypertrophy and ventricular disfunction. Increased chamber size may be demonstrated on echocardiogram with a systolic ejection murmur. Peripheral artery stenosis may be associated with reduced exercise tolerance, cardiac murmurs, and, possibly, pulmonary hypertension. Occasionally, congenital anomalies of the heart, bones, and kidneys also are found. These patients have abnormal autonomic modulation, reflected by an increased heart rate and a pronounced reduction in heart rate variability.^[2]

The presence of dental abnormalities such as talon cusps, macrodontia, and aberrant tooth morphology has been described.^[3]

Acquired generalized lipodystrophy

Generalized lipodystrophy often is preceded by an illness and, in many instances, an infection. The fat loss becomes apparent either focally or diffusely, usually beginning in adolescence or early adult life.

Most of the features of the congenital form may occur, but in the acquired form, neurologic, cardiac, and renal abnormalities usually are absent. Bone age is normal and genital hypertrophy is absent. AN to varying degrees probably is a constant finding in acquired and congenital forms.

Autoimmune disorders also may be common, including Coombs-positive hemolytic anemia and chronic nephritis; however, great variability exists in the immunologic abnormalities in patients with the acquired form. Patients with the acquired form of generalized lipodystrophy also are prone to infection.