| Abstract|| |
We report the association of partial lipodystrophy (PL) and nephritis in an 11-year-old boy. He had symmetric absence of facial fat with retention of adipose tissue in the arms, chest, abdomen and hips associated with macroscopic hematuria, proteinuria combined with depression of the complement C3 level. The patient had rapidly progressive glomerulonephritis (RPGN) and the histopathological study showed findings of mesangiocapillary glomerulonephritis (MCGN) and crescents. We managed and followed up this patient for three years. At the last follow-up visit, he still has mild proteinuria and microscopic hematuria and stable renal function.
|How to cite this article:|
Hasan MA, Al Raqad M. Partial Lipodystrophy and Rapidly Progressive Nephritis. Saudi J Kidney Dis Transpl 2001;12:183-6
| Introduction|| |
Lipodystrophy is remarkable for unusual metabolic associations. Weir Michell  first described the condition in 1885. The syndrome of partial lipodystrophy (PL) is not considered as benign as previously thought. For example, Senior et al  reported a series of 25 patients with lipodystrophy of whom 14 had renal disease. Generalized lipodystrophy, a rare condition, was first reported in Saudi literature in 1992. 
Girls are about four times more frequently affected with PL than boys with the usual age of onset between 5 and 15 years. Chronic glomerulonephritis develops at some stage in about 25% of the cases.  The occurrence of PL, C3 nephritic factor, and membranoproliferative glomerulonephritis, whether singly or in any combination, is usually sporadic.  PL is associated with a number of other abnormalities including diabetes mellitus, hirsutism, pigmentation, and hepatosplenomegaly. 
We report in this communication a case of PL, which is, to the best of our knowledge, the first from Jordan.
| Case report and hospital course|| |
An 11-year-old boy, born to consanguineously related Jordanian parents, was apparently healthy at birth. The patient is the eldest of three siblings who are healthy. The patient developed well and attained height and weight at 75 th and 90 th percentile, respectively.
At nine years of age he started to develop wasting of subcutaneous fat of the face, head and occipito-parietal region. It was only two months later when he presented to the out-patient department with global headache, generalized fatigability, periorbital edema and dark brown colored urine. There was a striking facial subcutaneous wasting in comparison with the normal appearance on the rest of the body [Figure - 1]. The patient was drowsy and the blood pressure was at the 95 th percentile for his age. However, he had normal fundoscopic examination and no sensory neural hearing loss.
Investigations showed the following: hemoglobin 110 gm/L, platelets 246,000/µl, blood urea nitrogen (BUN) 13.2 mmol/L, creatinine (Cr) 210 µmol/L, total protein 56 g/L, albumin 32 g/L, serum K+ 3.7 mmol/L, serum cholesterol 11.2 mmol/L and serum triglycerides 2.2 mmol/L. The fasting and postprandial blood glucose levels were normal with relatively high serum insulin around 40 µg/ml. The serum HbA1c was 4%. There was +3 Albumin in the urine with abundant red blood cells. C3 level was below detectable level with normal C4. Hepatitis B surface antigen was negative.
Over the following few days, the patient had further deterioration in his general condition, with oliguria and elevated blood pressure. Serum BUN increased to 35 mmol/L, Cr to 620 µmol/L and K + was 5.6mmol/L. Kidney biopsy was performed, and a 40 glomeruli specimen was examined by light microscopy. The glomeruli were diffusely enlarged with mesangial and endothelial cell proliferation as well as polymorphonuclear cell infiltrate. Over 50% of the glomeruli showed cellular crescents and blood vessels appeared narrowed [Figure - 2].
Three doses of pulse methyl prednisolone 30 mg/kg every other day were administered followed by oral prednisolone 2 mg/kg/day for three months. The patient showed remarkable clinical and biochemical response; serum C3 complement component level became normal. The kidney function tests on completion of the prednisolone course, three months after initial presentation, were as follows: Cr 106 µmol/L, BUN 13.2 mmol/L, urine 3+ albumin with microscopic hematuria. The steroids were tapered down and discontinued.
Shortly after discontinuation of prednisolone, he was admitted once again with generalized edema, oliguria, ascitis, hypertensive encephalopathy and deterioration of his kidney function with Cr 290 µmol/L and BUN 32 mmol/L. He was given another 3day course of methyl prednisolone pulse therapy, followed by 2 mg/kg/day oral prednisolone for six months. The kidney biopsy was not repeated.
Again the patient showed remarkable recovery with the return of his kidney function tests to normal. Prednisolone was finally discontinued after six months. Three years after presentation, our patient still has mild proteinuria associated with microscopic hematuria and his blood pressure is well controlled on 0.5 mg/kg/day propranolol. Follow-up kidney biopsy one year after the first episode showed features consistent with inactive glomerulonephritis [Figure - 3].
| Discussion|| |
To our knowledge, this is the first reported case of PL and RPGN. RPGN is not a common renal disease,  accounting for 27% of renal biopsies in most series, and smaller proportion of all patient with endstage renal disease. It is defined as any glomerular disease characterized by extensive crescent (usually over 50%) as the principal histological finding and a rapid loss of renal function (usually a 50% decline in GFR within three months as the clinical correlate).  Our patient fulfilled the above mentioned criteria in the first episode although kidney biopsy was not taken in the second relapse. It has been reported that the clinical course of RPGN cannot be anticipated by serum complement profiles, the presence of C3 nephritic factor, or partial lipodystrophy. 
In most reported cases, , lipodystrophy antedates the development of nephritis by few years; in our patient it was only two months. Serum C3 was not detectable in both episodes of the disease, with a normal C4. The complement levels returned to normal during remissions, suggesting activation of the alternative pathway during both episodes. Sissons et al  investigated serum complement in 25 patients with various forms of lipodystrophy: three patients showed no abnormality, a single patient with PL had evidence of the classical complement pathway activation and the rest had low C3 and normal C4 concentrations. Seven patients had overt nephritis; renal biopsy obtained in six showed mesangiocapillary nephritis in all. Presumably, C3 primary activation may result in prolonged hypocomplementemia and is directly responsible for both loss of subcutaneous fat and glomerular disease. 
Therapy of RPGN remains largely empiric, due to the lack of controlled studies. There has been consensus  on the "pulse therapy" in idiopathic RPGN with or without immune deposits. Most studies have used 30 mg/kg given intravenously three times on alternate days, followed by oral prednisolone in conventional doses, which is tapered over several months. In our patient, the above-mentioned regimen has shown remarkable recovery over three-year follow-up with satisfactory clinical and biochemical results.
Our patient had normal bone age and growth hormone level after sleep. The patient had normal fasting and postprandial blood glucose with simultaneously elevated level of serum insulin. Hyperinsulinism is considered when serum blood glucose concentration is less than four times the serum insulin concentration.  Accordingly, our patient had hyperinsulinemia. Tsukahara et al,  and Oseid et al  showed decreased binding of insulin to its receptor in patients with congenital generalized lipodystrophy both in vivo and on cultured fibroblast, lymphocytes and mononuclear leukocytes. HbA1c was normal in our case, in contrast to the Saudi patient  who had HbA1c of 18% and 12% at few months of age an after two years of follow-up, respectively.
This is the first patient in whom the coexistence of PL and RPGN is present at least in Jordan. Wasting of the adipose tissue of the face in a patient with puffiness, malaise and dark brown urine should raise the possibility of associated nephritis and PL.
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Mjalli A Hasan
Pediatric Consultant & Endocrinology, King Hussein Medical Center, P.O. Box 6080, Zarka
[Figure - 1], [Figure - 2], [Figure - 3]