March 1992, Volume 42, Issue 3

Case Reports

CONGENITAL GENERALIZED LIPODYSTROPHY

Naseem Jafri  ( Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi. )
Zohra Zaidi  ( Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi. )

Clinical features of congenital generalized lipodystrophy, a rare disorder, first described by Zeigler1 include loss of subcutaneous fat, hepatomegaly, in­creased bone growth, hyperlipaemia and, later, diabetes. The inheritance is probably autosomal recessive2. Generalized lipodystrophy may involve the dien­cephalon. A probable defect in the hypothalamus may lead to increased levels of hypothalamic releasing factors in the peripheral blood2.

CASE REPORT

A two year four month old girl of consanguineous parents, was seen at the Jinnah Postgraduate Medical Centre, Karachi. She weighed 2.8 kg after normal full term gestation, but lacked demonstratable subcutaneous fat at birth. Her miles stones were normal, but her rate of growth was more than other children of her age and appetite was voracious. Her height was 90 cm, weight 19 kg. On examination there was apparent loss of sub­cutaneous fat (Figure 1)

generalized hypertrichosis, but scalp hair was abundant and curly (Figure 2).

Mild acanthosis nigricans was present in the axillae (Figure 3).

She had prominent muscles, veins and teeth and had a pointed chin. Abdomen was protuberant, liver was 8 cms enlarged and no splenomegaly. Clitoris was slightly enlarged (Figure 4).

The patient appeared mentally retarded. Parents were normal and no other siblings affected. There was no history of fat atrophy in the family. Investigations showed normal blood count and urine analysis. Fasting blood sugar was 87 mg%, liver functions showed no abnormality. Total lipids were 724 mg%, cholesterol 151 mg%, triglycerides were elevated 253 mg% (normal 70-150 mg%). Blood urea 22 mg%, T3 and T4 were 1.6 ng/ml and 10.6 meg/dl respectively. Urinary 17 ketosteroids level was 7.6 ng/24 hrs and urine creatinine 109 mg%, x-ray skull was normal. Ultrasound of the abdomen showed enlarged homogenous liver with normal echopattern and normal spleen. Both kidneys were enlarged, right kidney was 9. lx 3.8 cm, left kidney 8.1x3.4 cm, E.C.G. was normal, l.Q. was 62. Biopsy of the skin showed an absence of subcutaneous fat. Hyper-in­sulinaemia was noted 148.2 IU/ml (normal 3-35 IU/ml). She was treated with pimozide 2 rug once daily for about a year. During this period, her appetite decreased, fat started to appear on the face and buttocks. Serum triglyceride levels decreased from 253 mg% to 168 mg%. On withdrawal of the drug, there was a return of many characteristics of the disease, There was a loss of subcutaneous fat, triglyceride level increased to 353 mg%, total lipids to 1430 mg%. These findings indicate that a prolonged treatment is required for continued clinical suppression of the disease.

DISCUSSION

Various etiologies for the syndrome include excess of hypothalamic releasing factors, an inherited or ac­quired anomaly in the peripheral insulin response, increased levels of fat mobilising factors and others3. Pimozide was given in this case on the basis that due to deranged hypothalamic catecholamine mechanism dopamine accumulates in the brain, which may result in an excess of hypothalamic releasing factors in the peripheral blood. Treatment with pimozide eliminated the releasing factors, corrected most of the abnormal blood chemistry and led to a return of subcutaneous fat. On withdrawal of the drug most of the symptoms reappeared. Prolonged treatment is apparently required for the continued clinical suppresion of the disease4. Other drugs used in the treatment of congenital generalised lipodystrophy arc chlorpromazine, fenfluramine, prolonged subcutaneous infusion of in­sulin and plasmaphoresis1-5. Involvement of the nervous system is manifested by diffuse gliosis of the cerebrum and dilatation of the ventricles6 and increase of growth hormone7. Although growth hormone levels have been normal in most of the cases3,8, presence of acanthosis nigricans may also point to a neuroendocrinal disorder. The other important features of the disease are hepatomegaly and hyperlipaemia. Hepatomegaly is due to fatty infiltration which may lead to portal cirrhosis2. The increase in lipids seems to be confined to neutral fats. In some cases fatty acids and cholesterol were also raised7. Most cases of congenital generalised lipodystrophy develop insulin resistant nonketotic diabetes at puberty1-10. The disease should be differentiated from progeria, metageria, congenital muscular hypertrophy and then­ cephalic syndrome of infancy. Combination of biochemi­cal and clinical pictures makes the diagnosis easier to differentiate.

REFERENCES

1. Huseman, C, Johanson, A., varma, M. and Blizzard, R.M. congenital lipodystrophy; an endocrineatudy in three siblings.). Pediatr., 1978; 93:221-6.
2. Brunzell, J.D., Shankle, S.W. and Bethune, I.E. Congenital generalised lipodystrophy, accompanied by cystic angiomatosis. Ann. intern. Med., 1968; 69:501-16.
3. Rossini, LA., Self, 3., Akoki, T.T., Goldman, R.F., Newmark, S.R., Meguid, M.M., Soeldner, 5. and cahill, G.F. Metabolic and endocrine studies in a case of lipoatrophic diabetes. Metabolism, 1977; 26:637.
4. Trygatad, 0. and Foss, I. Congenital generalised lipodystrophy and experimental lipostrophicdiabetea in rabbita treatedsuccessfullywith fenliuramine. Acta Endocrinol., 1977; 85:436.
5. KIar, A., Corcos, A.P., Gross-Kieselstein, a, Reifen, R.M. Navon, P. and Branski, D. Near normalisation of metabolic abnormalities by prolonged CS 11 in a girl with congenital lipodystrophy. Diabetes care, 1987; 10:257-9.
6. Reed Wib., Dexter, it, Corley, C. and Fish, C. Congenital lipoatrophic diabetes with acanthosis Migricans. Arch. Dermatol., 1965; 91:326.
7. Tzaguornia, M. and George, 3. Increased growth hormone in partial and total lipodyatrophy. Diabetes, 1973; 22:388.
8. Soler, NO., Wortsman, J. and Chopra, I.J. Upoatrophic diabetes; endocrine dysfunc­tion and the response to control of hypertriglyceridemia. Metabolism, 1982; 31:29-24.
9. Griffith, H.J. and Roasini, AL A case of lipoatrophic diabetes. Diagn. Radiol., 1975; 114:329.
10. KIar, A., Livini, N., Gross-Kieselstein, B., Navon, P., Shahin, A. and Branski, D. Ultrastructural abnormalities of theliverin total lipodystrophy.Arch. Pathol. Lab. Med.,1987; 111:197-9.

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