Only 13 confirmed cases of primary enterokinase deficiency have been reported since the condition was first described in 1969.  Secondary enterokinase deficiency has been reported in patients with partial or total villous atrophy; however, enterokinase activity is usually not significantly affected in these conditions. A previously described patient developed celiac disease at age 25 years, but enterokinase levels remained low after normalization of intestinal mucosa with gluten-free diet.  Enterokinase, also known as enteropeptidase, is a key enzyme for intestinal digestion of proteins. Therefore, enterokinase deficiency causes severe protein malabsorption with poor growth and development.
Enterokinase is synthesized by the enterocytes of the proximal small intestine and can be found in the brush border membrane and as a soluble form in intestinal fluid. Human enterokinase appears to be a disulfide-linked heterodimer, composed of a 784 amino acid heavy chain and a 235 amino acid light chain, derived by processing of the single-chain precursor. According to the deduced amino acid sequence, enteropeptidase is a serine protease. The active 2-chain enteropeptidase is derived from the single-chain precursor proenteropeptidase. It is activated by duodenase, a serine protease expressed in the duodenum. 
Duodenopancreatic reflux of the duodenal contents could result in trypsinogen activation by enteropeptidase within the pancreas, followed by acute pancreatitis.  Beta-site APP-cleaving enzyme1 (BACE1), a protease that has been closely linked to the pathogenesis of Alzheimer disease but highly expressed in pancreatic acinar cells, could possibly protect the pancreas from premature trypsinogen activation. 
Enterokinase is secreted by the mucosa of the small intestine. It is absent in crypts but significant in villous enterocytes and maximal in the upper half of the villi, especially on the brush border. The enzyme catalyzes the conversion of trypsinogen to its active product, trypsin. In turn, trypsin activates the other pancreatic proteolytic zymogens (chymotrypsinogen, procarboxypeptidase, proelastase) to chymotrypsin, carboxypeptidase, and elastase.
Enterokinase deficiency seriously impairs protein absorption. Proteinase-activated receptor 2 is present at the apical and basolateral membrane of enterocytes; activation of this receptor by trypsin stimulates enterocytes to secrete eicosanoids, which act locally in the intestinal wall to regulate epithelial growth. Therefore, in addition to its purely digestive role, enterokinase localization on the luminal surface of the duodenal villi possibly contributes to enterocyte growth by generating active trypsin on the cell surface.
The human genetic locus appears to be close to the gene for beta-amyloid precursor protein at band 21q.21.2. The human proenteropeptidase gene consists of 25 exons (24 introns) and spans around 88 kb of genomic DNA sequence.  Duodenase mutations that result in defective activation of proenteropeptidase may possibly lead to disease, similar to enterokinase deficiency.
Only 13 cases of primary enterokinase deficiency have been reported. Three additional patients were reported with a similar clinical picture but with unmeasured intestinal enterokinase activity.
Prognosis is good with adequate treatment.
No sex predilection is evident among the few reported cases.
With one reported exception, affected patients present at birth with diarrhea and failure to thrive.  That exception was the sister of an affected boy; she was aged 5 months at onset and was diagnosed at age 8 years.