Alagille syndrome is characterized by the association of chronic
cholestasis with a
paucity of interlobular bile ducts and a distinctive
facies together with cardiovascular, skeletal and
eye abnormalities. We examined the kidneys of 26 patients with this syndrome; 22 were under 3 years of age and 4 were 4, 6, 12 and 17 years old, respectively. Eighteen showed glomerular lesions of variable severity characterized by a mesangiolipidosis. In the 8 lesser affected patients light microscopy (LM) disclosed a fibrillar appearance of the mesangium, and electron microscopy (EM) showed
lipid vacuoles widespread in the mesangial matrix. In the 10 patients who were affected to a greater degree LM and EM showed, in addition to the mesangial matrix changes, the presence of mesangial foam cells. Clinical signs of renal involvement were mild in all patients except for one who died from
chronic renal failure at 8 months of age. The extent of mesangiolipidosis was not related to age but to the degree of
cholestasis, the most severe lesions being observed in patients aged 3, 6, 8, and 14 months. The glomerular lesions observed in
Alagille syndrome are strikingly similar to those observed in adults with
lecithin-
cholesterol acyl
transferase deficiency and other conditions characterized by an increase in plasma
lipoproteins rich in free
cholesterol and in
phospholipids. We conclude that glomerular involvement should be added to the characteristic features of
Alagille syndrome. Also we found that the
lipid deposition in the glomeruli of patients with
Alagille syndrome is related to an abnormal lipid metabolism, which is the consequence of severe
cholestasis. The most striking feature of our study is the early detection of the glomerular lesions, contrasting with the lack of overt clinical renal disease.
Renal failure may be a major complication for patients with this syndrome in adulthood.