Congenital lipodystrophy with defective leucocyte function (a case report).
A 6 1/2 year old female child with congenital lipodystrophy is being presented. The noteworthy feature in this case was the defective leucocyte function and its association with tuberculous pericardial effusion.
Lipodystrophy is a rare syndrome characterised by decrease in adipose tissue, generalised muscular hypertrophy, tall stature and hepatosplenomegaly.
A 6 ˝ year old female child, born of a consanguinous marriage was admitted with the complaints of high fever, breathlessness, abdominal distention and oedema of the feet of 3 days' duration. She was treated for an abscess on the thigh 15 days prior to the admission. At the age of 2 months, she had an abscess, which was complicated by bronchopneumonia. Her weight was 22 kg > 95th per centile) and height was 120 cm (> 95th percentile). On examination she was found to have oedema of the feet, excessive hair over the hands and legs, prominent muscles, phlehomegaly, generalised loss of subcutaneous fat, broad hands, short stubby fingers, prominent jaw (See [Figures:1 and [Figures:2]) and acanthosis mgrans in the axilla. Genitalia were normal. Her pulse rate was 120/min, blood pressure was 120/80 mm Hg and JVP was raised. The apex beat was not palpable, cardiac dullness was found to be increased, heart sounds were distant and of low intensity. No murmurs were diagnosed. She had massive ascites and a firm hepatosplenomegaly of 15 cm each. (See [Figures:1]) The respiratory and central nervous systems were normal. The child was of average intelligence.
On investigation, haemoglobin was found to he 11.5 gms/dl, WBC 19.400/mm, with polymorphs 72%, ESR 42 mm at the end of 1 hour (Westergrene). Mantoux test was negative. The renal chemistry and liver function tests were normal, scrum cholesterol and triglyceride levels were 84 and 128 mg% respectively. Total serum proteins were 6.2 gm% with albumin of 1.93 gm%. Random blood sugar was 200 mg% and the glucose tolerance curve was abnormal. Urine sugar measured by Benedict's test was 1+. X-ray chest showed massive cardiomegaly suggestive of pericardial effusion; ECG showed low voltage and elevated ST segments. Skeletal survey revealed a bone age of 9 years. Ultrasonogram showed normal sized kidney.
Pericardial fluid was haemorrhagic and caseous material. The fluid protein was 4 gm%. Culture showed no growth. The pericardial fluid was positive for TB antigen. The biopsy showed chronic inflammatory changes.
Specialised investigations were performed. Serum complement (C3) levels were normal. Serum IgA level was 240 mg/dl (normal range: 50-300 mg/dl) and IgM was 138 mg/dl (normal range: 70-160 mg/dl) T cell function as detected by rosette formation was normal. Polymorphonuclear function showed reduced phagocytosis of 25% (normal: 34.2% + 2.5) and intracellular killing of 16.66% (normal: 33.98% + 5.8). Monocyte function was also reduced, phagocytosis being 21.7% (normal: 28.2% + 4.36) and intracellular killing being 51.72% (normal: 96.9% + 5.9).
Serum insulin levels were 7 microunit/ml. (normal: 3-35 microunit/ml). Endocrine profiles of thyroid, adrenals and gonads were normal.
The patient was treated with antibiotics and anti-tubercular drugs. Steroids were withheld. She improved with this therapy and after pericardial drainage. Liver and spleen were reduced to 9 cm. Diabetes mellitus was managed by dietic restriction.
This syndrome was first described by Lawrence in 1946. The acquired form is now known as Seip Lawrence Syndrome. It can develop following viral infections while the congenital form is autosomal receisive. Both sexes are equally affected. About 80 cases of this syndrome have been described in the world literature to date.
Lawrence laid down the following criteria for diagnosis: 1) generalised absence of fat 2) insulin resistant diabetes mellitus 3) absence of ketosis 4) increased basal metabolic rate 5) severe hepatosplenomegaly and hyperlipidaemia. All these criteria were present in our case.
Different hypotheses have been put forward to explain the various findings in this syndrome. The inheritance is autosomal recessive possibly a missing gene or an enzyme may cause the abnormalities. Louis et al, have isolated a polypeptide having adipokinetic, diabetogenic and antfinsulin properties. This has been isolated in the urine of some cases. Extracts from the anterior and posterior pituitary showed presence of lipid mobilising factors. It has been shown that, lipodystrophy is induced by a compound similar to cachetin (tumour necrosis factor). This has powerful inhibitory effects on lipoprotein lipase and causes fat depletion and hyperlipidaemia when injected in animals. Children with lipodystrophy have apparent gigantism. Though level of growth hormones is normal, its structural changes lead to mobilisation of fat. Seip and Trygstad reported abnormalities in the region of the pituitary, third ventricle and basal cisterns. Claude Bernard demonstrated discrete lipid centres on the inferior surface of the hypothalamus which may be responsible for lipid mobilisation, hyperlipidaemia, hepatomegaly and nephromegaly in experimental animals. The deranged hypothalamic mechanisms lead to increase in releasing factors (MSH, FSH and CRF), which also disturb feed back regulation.
Insulin resistance in lipodystrophy develops as a result of alteration in the intracellular signals due to absence of cell membrane or receptors keeping the insulin levels normal or high. Insulin resistance spares the liver and skeletal muscles and hence ketosis does not develop. Thyroid hormones are normal. BMR is high due to abnormal thermogenesis. Fatty infiltration leads to enlargement of liver and spleen, which steadily progresses to cirrhosis and portal hypertension. Heart shows glycogen deposition.
The striking feature in our case was lowered polymorphonuclear and monocytic function, which was responsible for frequent pyogenic infection even though the patient had normal complements (C3) and 'T' cells.
Various drugs like punozide, and fenfluramine which reduce dopamine in the hypothalamus have been tried. Alternate day steroids have been recommended and propranalol can be used to control hypertension. Diabetes is managed by dietary restriction.
Death usually results from hepatic or renal failure, haematemesis and/or portal hypertensin. Diabetes, which is resistant to insulin, can lead to renal, retinal and neurological complications.
We wish to thank the Dean, Seth GS Medical College, King Edward Memorial Hospital, for giving us permission to publish this case report. We also express our thanks to Dr S.D. Bandarkar, Head of Department of Endocrinology, for his assistance.