Clinical Quiz

Abstract

A 3.5-year-old boy was admitted because of fever and urinary symptoms. He was the first offspring of his healthy first-cousin parents, with a normal birth weight. After 2 months of breastfeeding, he was placed on formula milk. At 7 months of age, he had been admitted because of urinary-tract infection (UTI), failure to thrive (FTT), and steatorrhea. Radiological study showed a stone in his left kidney. His UTI was treated with antibiotics but his parents refused more studies. This time, he had steatorrhea and FTT (weight, height, and head circumference below the 5th percentile). In physical examinations, his heart and lungs were normal and there was no organomegaly or lymphadenopathy, but we did notice diminished deep-tendon reflexes. Further studies showed normal sweat test; urine white blood cells (WBC), 25 cells/high-power field; urine bacteria, >105/ml; serum WBC, 7200 cells/μl; Hg, 10.7 g/dl; prothrombin time (PT) activity, 84%; serum cholesterol, 28 mg/dl (45-82 mg/dl); triglyceride, 9 mg/dl (30-86 mg/dl); low-density lipoprotein, 16 mg/dl (60-140 mg/dl); high-density lipoprotein, 10 mg/dl (35-55 mg/dl). His parents lipoprotein profiles were normal. His peripheral blood smear and intestinal biopsy are shown in Figures 1 and 2. Meanwhile, his voiding cystouretherogram was normal and in radiologic study he had two stones in his left kidney. His UTI was treated with antibiotics and lithotripsy was done. The stone analysis showed a mixed stone of uric acid, calcium oxalate, and triple-phosphate.FIG. 1: Acanthocytes in peripheral blood smearFIG. 2: Lipid laden enterocytes in intestinal biopsyWhat is the diagnosis? A. Intestinal lymphangiectasia B. Cystic fibrosis C. Anderson's disease D. Abetalipoproteinemia E. Schwachman-Diamond syndrome F. Celiac disease ANSWER/DISCUSSION ANSWER: Abetalipoproteinemia (ABL). In fact, in lipoprotein electrophoresis there was an absence of apolipoprotein B. COMMENT: ABL is a rare autosomal recessive disorder caused by mutation in the gene of microsomal triglyceride transfer protein, which transfers lipids to apolipoprotein B (apoB). Abnormality in this protein will cause a virtual absence of apoB-containing lipoproteins [chylomicron, very-low-density lipoprotein (VLDL), (LDL)] and extremely low levels of triglyceride and cholesterol. Inability of intestinal enterocytes to secrete long-chain fatty acids into the blood will lead to an accumulation of lipids in the enterocytes (lipid-laden enterocytes), malabsorption of lipids and fat-soluble vitamins, steatorrhea, and FTT. In fact, most of the symptoms of ABL are due to vitamin deficiency, especially vitamin E. These findings are: bizarrely shaped red blood cells (acanthocytes) and mild anemia; neurologic problems starting with diminished deep-tendon reflexes, followed by gradual loss of distal lower-extremity vibratory and proprioception senses; dysmetria; ataxia, and spastic gait, and ophthalmologic problems (decreased night and color vision, progressive retinitis pigmentosa). Diagnosis is made by extremely low levels of cholesterol, triglyceride, VLDL, LDL, and apoB. Therapy includes avoidance of long-chain fatty acids and administration of fat-soluble vitamins. (1) On the other hand, hyperoxaluria and subsequent oxalate lithiasis can be due to increased oxalate production or absorption. Ca2+ in the intestinal lumen, by binding to oxalate and forming insoluble salts, decreases absorption of oxalate. In ABL (as in other fat-malabsorption disorders), excessive amounts of fat in the colon combine with Ca2+, leading to lower oxalate salt formation and increased oxalate absorption. This will lead to hyperoxaluria and oxalate stone formation. (2) Uric acid is responsible for formation of another type of kidney stone. The main determinant factor of uric acid supersaturation in the urine and subsequent stone formation is low urine pH. Decreased urine volume, high-purine diet, or increased endogenous uric acid production are other causes of uric acid stone formation. Unabsorbed dietary fatty acids in the intestinal lumen can cause an osmotic diarrhea and patients with chronic diarrhea are particularly at risk from uric acid stones, because they are often dehydrated, so they have a chronic metabolic acidosis and acidic urine. They also have lower urine volume. The dimensions of uric acid crystals closely match those of calcium oxalate and it has been suggested that the uric acid crystals promote heterogeneous nucleation of calcium. Finally, obstruction of urinary system by stones and subsequent stasis would be a risk factor for UTI and, in the presence of urea-splitting bacteria, urea and H+ could form triple-phosphate stones. (3) Two other inherited disorders that affect apoB-containing lipoproteins are Anderson's disease and familial hypobetalipoproteinemia. In Anderson's disease, only apoB48 is absent and acanthosytosis is rare. Familial hypobetalipoproteinemia is an autosomal co-dominant disorder. Patients with homozygous familial hypobetalipoproteinemia have exactly the same clinical picture as patients with ABL, but their parents, who are heterozygotes, have plasma concentrations of apoB and LDL that are one-quarter to one-half the normal levels.