LIPASE AND COLIPASE, CONGENITAL ABSENCE OF PANCREATIC, INCLUDED
PL DEFICIENCY PANCREATIC COLIPASE DEFICIENCY, INCLUDED
LIPASE AND COLIPASE, DEFICIENCY OF, INCLUDED
COLIPASE, CONGENITAL ABSENCE OF PANCREATIC, INCLUDED
LIPASE, CONGENITAL ABSENCE OF PANCREATIC
PNLIPD
Congenital pancreatic lipase deficiency is a rare, monoenzymatic form of exocrine pancreatic failure. All reported patients have presented with similar symptoms and clinical findings, including oily/greasy stools from infancy or early childhood and the absence of discernable pancreatic ... Congenital pancreatic lipase deficiency is a rare, monoenzymatic form of exocrine pancreatic failure. All reported patients have presented with similar symptoms and clinical findings, including oily/greasy stools from infancy or early childhood and the absence of discernable pancreatic disease. Failure to thrive has not been observed. Analyses of duodenal contents consistently show a marked decrease of pancreatic lipolytic activity (summary by Figarella et al., 1980).
Sheldon (1964) reported 4 children, a brother and sister and 2 brothers, from 2 unrelated nonconsanguineous families, who had congenital pancreatic lipase (246600) deficiency. From early infancy, all 4 were noted to have a greasy quality to their ... Sheldon (1964) reported 4 children, a brother and sister and 2 brothers, from 2 unrelated nonconsanguineous families, who had congenital pancreatic lipase (246600) deficiency. From early infancy, all 4 were noted to have a greasy quality to their stools, with liquid oil separating from the stool and solidifying as the stool cooled. At an age when most children were gaining control of their bowel movements, these children were handicapped by soiling their clothes with liquid oil that they were unable to restrain. Analysis of duodenal fluid in the children showed total absence of pancreatic lipase in 1 boy and less than half the normal amount in the other 3 children. Sheldon (1964) stated that the disorder could be distinguished from other causes of steatorrhea such as fibrocystic disease of the pancreas and celiac disease due to satisfactory growth, lack of abdominal distention, and lack of respiratory infections leading to lung damage. The author also noted that despite greatly decreased production of pancreatic lipase, fat absorption in the 3 children in whom it was analyzed was approximately 70%, suggesting action of lipase derived from the stomach and intestine. Treatment with lipase given as pancreatin improved fat absorption, although not to normal levels, and brought the oily condition of the stools and soiling under control; dietary control of fat intake, however, remained necessary, with any excess intake leading to a return of oil in the stools and soiling. The condition was believed to be autosomal recessive. Rey et al. (1966) reported a 10-year-old boy who at 3 years of age developed episodes of abundant, greasy diarrhea that coincided with asthmatic attacks. By 5 years of age, his stools were consistently greasy and voluminous, occurring once or twice a day with excessive oil that separated out, and despite being continent, his clothes were stained with oil seepage. A sweat chloride test was within normal limits, and analysis of duodenal fluid showed normal secretion of bicarbonates, slightly decreased trypsin (see 276000) and amylase (see 104650) activity, and virtually absent lipase activity. Absorption of sugars was normal, and a barium study of the small intestine and jejunal and pancreatic biopsies were all normal. The fat in his stools decreased by 50% when pancreatic extract was added to his diet, but increased immediately to previous levels when the treatment was stopped. Rey et al. (1966) noted that the delayed onset in this patient was suggestive of an acquired disorder, but the persistent absence of pancreatic lipase at 8 years of age showed similarity to the 4 patients described by Sheldon (1964). Balzer (1967) studied an 8-year-old girl who had abundant fatty stools from around 1 year of age, which did not improve with the use of charcoal. She had normal growth and development. Pancreatic function tests showed complete absence of lipase activity, with slightly reduced protease activity and normal amylase activity; lipase activity remained very low even after vagal stimulation. Follow-up for more than a decade showed continued symptoms, but good growth and development; she did well in school and participated in sports. Based on the history and findings, Balzer (1967) concluded that the patient had a congenital enzymopathy, most likely autosomal recessive in nature, since both parents were healthy and the patient had 2 healthy brothers. Larbre et al. (1969) reported a 10-year-old girl with congenital lipase deficiency who developed chronic greasy diarrhea at 10 months of age when breastfeeding was discontinued and whole milk introduced into her diet. She was otherwise healthy and had normal growth and development; she had 2 younger brothers who were healthy. The coefficient of fat absorption in the patient was 62%, and analysis of enzyme activity in her duodenal fluid demonstrated an almost total lack of lipase activity. Symptomatic improvement was minimal with pancreatic extract alone, and it was discontinued by the family; the patient's mother stated that limiting her daughter's intake of fats to 40 to 50 g per day normalized her stools. Larbre et al. (1969) noted that similar to previous reports, there was a striking discrepancy between the voluminous steatorrhea and the patient's overall good state of health. Verger et al. (1971) reported a 9-year-old boy who had severe steatorrhea from 2 years of age, in whom examination of duodenal fluid revealed decreased pancreatic lipase activity. In contrast to previous reports, replacing dietary animal fat with corn oil increased the patient's coefficient of fat absorption from 60% to 82%. Effective treatment measures included high doses of pancreatic extract and extreme reduction of dietary fat, to 20 g of corn oil per day. In a 9-year-old girl who had large greasy stools from 3 months of age and complete lack of pancreatic lipase activity in duodenal fluid, Figarella et al. (1972) demonstrated that pancreatic colipase (120105) was present and unaffected. Muller et al. (1975) reported a patient in whom, despite complete absence of pancreatic lipase, more than 50% of dietary fat was absorbed. Studies to elucidate the mechanism of fat absorption suggested that in the absence of pancreatic lipase, gastric lipase (601980) and pancreatic esterase (114840) may play an important compensatory role in the absorption of dietary fat. Using immunologic and enzymatic techniques to study a 46-year-old man who had steatorrhea from at least age 20 years, Figarella et al. (1979) demonstrated a complete lack of pancreatic lipase, but normal levels of colipase. Duodenal fluid from the patient, in which no pancreatic lipase activity could be detected, was capable of reactivating pure pancreatic lipase inhibited by a high concentration of biliary salts, thus indicating the presence of colipase. In a 5.5-year-old boy of German parentage who from infancy had greasy/oily stools, Figarella et al. (1980) found absence of pancreatic lipase in duodenal contents after stimulation with secretin/pancreozymin. Colipase, however, was present, consistent with independent synthesis of the 2 enzymes. Stool bulk and frequency decreased while on a fat-reduced diet. Addition of exogenous lipase to a diet with normal fat content did not appreciably change stool weight and frequency. Lard as a major source of dietary fat did not cause overtly greasy/oily stools, whereas such stools were again produced after ingestion of butterfat. At 11 years of age, the child was well within normal growth and development, and continued on a fat-reduced diet. Figarella et al. (1980) suggested that the poor clinical response to exogenous lipase might be due in part to denaturation in the acid milieu of the stomach, with the remaining activity inadequate to normalize fat digestion. - Isolated Pancreatic Colipase Deficiency Hildebrand et al. (1982) studied 2 Assyrian brothers, born of consanguineous parents, in whom loose stools developed at 5 and 6 years of age, respectively. Evaluation revealed steatorrhea, and analysis of exocrine pancreatic enzymes in the small intestine revealed isolated colipase deficiency, with normal levels of amylase, chymotrypsin (601405), and lipase. Intraduodenal infusion of purified colipase improved fat digestion measured by the triolein breath test, and the sibs' steatorrhea decreased on treatment with enteric-coated pancreatic enzymes. Both boys had gallstones, possibly related to malabsorption of bile salts associated with pancreatic insufficiency. The older brother also had megaloblastic anemia due to vitamin B12 deficiency; the authors noted that defective absorption of vitamin B12 had been observed in patients with pancreatic insufficiency (Toskes et al., 1971), and suggested that colipase might be involved in its absorption. Hildebrand et al. (1982) stated that this was the first report of isolated colipase deficiency, and noted that either lipase or colipase deficiency results in the same pattern of decreased fat absorption. - Combined Congenital Pancreatic Lipase and Colipase Deficiency Ghishan et al. (1984) reported a 5-year-old boy who had a history of passing foul-smelling oily/greasy stools from birth. The stools became less greasy when skim milk feedings were begun at 2 months of age, but began again upon introduction of solid foods. Pancreatic stimulation tests showed that both lipase and colipase activities were less than 2% of normal values. The patient's fat absorption coefficient went from 50% to 82% upon supplementation with pancreatic enzymes. Ghishan et al. (1984) stated that this was the first report of congenital combined lipase and colipase deficiency. Ligumsky et al. (1990) described 2 brothers of Arab origin, born to nonconsanguineous parents, who had isolated congenital lipase and colipase deficiency. Both sibs, who were 15 years and 10 years old, had passed greasy stools from infancy but were otherwise healthy and normally developed. Both had voluminous steatorrhea and low serum carotene and vitamin E concentrations, although there were no clinical signs of any lipid-soluble vitamin deficiency. After exocrine pancreatic stimulation, lipase activity in duodenal fluid from both brothers was less than 1.5% of the control value and colipase activity was almost completely absent, whereas amylase, trypsin, bile salts, and pH values were normal. Ligumsky et al. (1990) noted that fat absorption in the sibs was 70% and 79%, respectively, suggesting that in these patients extrapancreatic sources of lipase, such as lingual and gastric lipase, may have an important compensating role in fat digestion.