Neurological Features and Enzyme Therapy in Patients With Endocrine and Exocrine Pancreas Dysfunction Due to CEL Mutations

Abstract

OBJECTIVE -To further define clinical features associated with the syndrome of diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl-ester lipase (CEL) gene and to assess the effects of pancreatic enzyme substitution therapy.RESEARCH DESIGN AND METHODS -Nine patients with CEL gene mutation, exocrine deficiency, and diabetes were treated and followed for 30 months.RESULTS -Treatment improved symptoms in seven of nine patients. Exocrine and endocrine function assessed by fecal elastase and A1C were not affected, although fecal lipid excretion was reduced. Vitamin E was low in all patients but increased with treatment (P Ͻ 0.001 at 30 months) and improved in five subjects. A predominantly demyelinating neuropathy was seen in a majority of patients, and carpal tunnel syndrome was common.CONCLUSIONS -Pancreatic enzyme substitution alleviated symptoms and malabsorption and normalized vitamin E levels. Glycemic control was not significantly affected. The CEL syndrome seems associated with a demyelinating neuropathology.

Severe Pancreatic Dysfunction But Compensated Nutritional Status in Monogenic Pancreatic Disease Caused by Carboxyl-Ester Lipase Mutations

“…Low levels of vitamin E have been previously described in CEL-MODY patients 6 with no observed clinical signs of associated vitamin E deficiency. 26 Although the negative correlation between pancreatic steatorrhea and vitamin E levels has been shown previously, 29,30 this is the first study to demonstrate the direct correlation between duodenal lipase activity and vitamin E deficiency. Low vitamin E levels are reported in both cystic fibrosis 31,32 and chronic pancreatitis 33 and are believed to be caused by a combination of increased vitamin E consumption and pancreatic malabsorption in these 2 conditions 34,35 and not only acinar dysfunction, as found in our study.…”

“…Pre-PERT weight loss has mostly been absent and with negligible improvement on weight and nutritional parameters on pancreatic enzyme supplements. 26 This minimal influence of severely reduced acinar function on malnutrition may partly be explained by compensatory increased food intake 25 and avoidance of symptom-provoking food elements (eg, food rich in fat) 2 as long as the intestinal absorptive capacity is intact and energy expenditure is not increased. This contrasts other conditions with pancreatic exocrine dysfunction and extrapancreatic manifestations, including chronic pancreatitis and cystic fibrosis, which may also affect nutrient intake, intestinal absorptive capacity, liver function, and energy expenditure 3,4,27, 28 We identified a strong relationship between acinar lipase levels and pre-PERT vitamin E levels.…”

Maturity onset diabetes of the young: identification and diagnosis

“…In one study pancreatic enzyme substitution alleviated fat malabsorption but glycaemic control was not affected. 86 To date only three families have been identified with CEL mutations causing MODY. 84,85 …”

Review on monogenic diabetes

“…Kruppel-like factor 11 (KLF11) is another transcription factor that regulates PDX1 (IPF1) transcription in b-cells. Heterozygous deletions in CEL cause both exocrine and endocrine pancreatic dysfunction [38,39]. Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes (CEL-MODY; MODY8) [37 ].…”