Multiple cases with various types of pediatric
malabsorption syndromes were evaluated. The clinical manifestations, laboratory findings, pathophysiology, and histopathological descriptions of each patient were analyzed in an effort to clear the pathogenesis of the
malabsorption syndromes and the treatments were undertaken. The cases studied, included one patient with
cystic fibrosis, two with
lactose intolerance with lactosuria (Durand type), one with primary intestinal lymphangiectasia, two with
familial hypobetalipoproteinemia, one with
Hartnup disease, one with congenital chroride
diarrhea, one with
acrodermatitis enteropathica, one with intestinal nodular lymphoid
hyperplasia (NLH), five with intractable
diarrhea of early infancy and four with
glycogenosis type Ia. Each case description and outcome is described below: 1. A 15-year-old Japanese boy with
cystic fibrosis presented with severe symptoms, including
pancreatic insufficiency,
bronchiectasis,
pneumothorax and
hemoptysis. His prognosis was poor. Analysis of the CFTR genes of this patient revealed a homozygous large deletion from intron 16 to 17b. 2. In the sibling case of Durand type
lactose intolerance, the subjects'disaccaridase activity of the small bowel, including
lactase, were within normal limits. The results of per oral and per intraduodenal
lactose tolerance tests confirmed lactosuria in both. These observations suggested, not only an abnormal gastric condition, but also duodenal and intestinal mucosal abnormal permeability of
lactose. 3. In the case of primary intestinal lymphangiectasia, the subject had a lymphedematous right arm and hand, a grossly coarsened mucosal pattern of the upper gastrointestinal tract (identified via radiologic examination) and the presence of lymphangiectasia (confirmed via duodenal mucosal biopsy). The major laboratory findings were
hypoalbuminemia, decreased
immunoglobulin levels and
lymphopenia resulting from loss of lymph fluid and
protein into the gastro-intestinal tract. 4. In two cases of heterozygous
familial hypobetalipoproteinemia, serum total
cholesterol and betalipoprotein levels were very low. The subjects presented with symptoms and signs of
acanthocytosis and fat malabsorption. Further, one subject had neurological abnormalities such as
mental retardation and severe convulsions. Treatment with MCT formula diet corrected the
lipid malabsorption. 5. A 5-year-old girl presented with
pellagra-like rashes,
mental retardation and
cerebellar ataxia. An oral
tryptophan (Trp) and
dipeptide (Trp-Phe) loading test were conducted and the renal clearance of
amino acids was also evaluated in this patient and in controls. Following the oral Trp loading test, plasma levels of Trp indicated a lower peak in the case, reaching a maximum at 60 minutes. On the other hand, the oral
dipeptide (Trp-Phe) loading test in the Hartnup patient showed the peak Trp plasma level was the same as the control subjects. The renal clearance of
neutral amino acids in this case increased to levels 5 to 35 times normal. 6. In the case of
congenital chloride diarrhea, the subject had secondary
lactose intolerance,
dehydration,
hyponatremia,
hypokalemia, hypochloremia, hyperreninemia and metabolic
alkalosis. The
chloride content of her fecal fluid was very high. The concentrations were 89-103 mEq/l. In contrast, her urine was
chloride-free. The subject's growth and development improved
after treatment with
lactose free formura and oral replacement of the fecal loses of water, NaCl and KCl. Unfortunately, the patient died of a small bowel
intussusception. The kidney histopathological finding was juxtaglomerular
hyperplasia by a necropsy. 7. In the case of
acrodermatitis enteropathica, the subject had characteristic skin lesions, low serum
zinc levels and ALPase activity. An oral ZnSO4 loading test and intestinal mucosal histology by a peroral biopsy were conducted. The serum
zinc peak level was 2 hours after the oral ZnSO4 loading test. Infant formula alone could not maintain normal serum
zinc ranges. Light microscopic studies of the intestinal villous architecture showed a normal pattern. However, ultrastructual examination of several epithelial cells revealed numerous intracellular vesicles. After
zinc therapy, these changes were decreased. The lesions were postulated as the secondary result of
zinc deficiency. 8. A 12-year-old girl presented with
hypogammaglobulinemia,
recurrent infections, chronic
diarrhea and intestinal NLH. A
barium meal and follow-through examination showed multiple nodules throughout the stomach and intestine. The nodules, all uniform in size, were 2 mm diameter. The barium enema did not show NLH in the colon. Mucosal biopsy of the stomach and jejunum revealed the typical histology of NLH in the lamina propria. Also,
achlorhydria was present in this patient and her serum
gastrin levels were very high; 315-775 pg/
ml. 9. In 4 cases of intractable
diarrhea in early infancy (by Avery G B), a jejunal biopsy showed shortening villi and nonspecific
enterocolitis. Some patients were found with only low
lactase or low
lactase and
sucrase levels. An electron microscope analysis of the small bowel in 2 cases showed alterations: increased pinocytosis in microvillus membranes and lysosomes by endocytosis of undigested
macromolecular substances. I postulated that the stated evidence was causative of this clinical profile. 10. I frequently observed
diarrhea as a clinical manifestation in
glycogenosis type Ia and
lipid malabsorption in one case. The light and electron photomicrographs showed intestinal absorption cells with the
glycogen deposits in the inferior devision of nuclei.