Alternative titles; symbols
SNOMEDCT: 124498007, 56661000; ORPHA: 168601; DO: 0111667;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 21q21.1 | Enterokinase deficiency | 226200 | Autosomal recessive | 3 | TMPRSS15 | 606635 |
A number sign (#) is used with this entry because of evidence that enterokinase deficiency is caused by compound heterozygous mutation in the serine protease-7 gene (PRSS7; 606635), which encodes proenterokinase, on chromosome 21q21.
Deficiency of enterokinase, a sequence-specific protease that activates trypsinogen (see 276000) and has a major role in protein digestion, is an autosomal recessive disorder characterized by severe protein malabsorption in early infancy, with failure to thrive, chronic diarrhea, and generalized edema. In adulthood, patients have normal body weight and no gastrointestinal symptoms, even when pancreatic enzyme supplements are discontinued (summary by Holzinger et al., 2002).
Hadorn et al. (1969) described a female infant with diarrhea, failure to thrive, and hypoproteinemic edema who was shown to have deficiency of intestinal enterokinase. The parents were not studied. Haworth et al. (1975) reported the cases of a brother and sister. Affected patients may show spontaneous improvement and normal growth after the age of 6 to 12 months. Affected sibs were reported by Lebenthal et al. (1976). Ghishan et al. (1983) reported the case of a 13-month-old infant. Only 8 cases had previously been reported. All reported patients have shown favorable response to pancreatic enzyme replacement. Almost all the patients presented at birth with diarrhea and failure to thrive. The most consistent laboratory finding was hypoproteinemia and about half the patients had edema.
Haworth et al. (1971) reported the case of a boy with enterokinase deficiency who thrived until he was weaned at 5 months of age. Moroz et al. (2001) reported that the patient described by Haworth et al. (1971) had also been diagnosed with celiac disease.
Holzinger et al. (2002) reported a follow-up of the families first described by Haworth et al. (1971, 1975). In adulthood the patients have normal body weight and no gastrointestinal symptoms, even when pancreatic enzyme supplements have been discontinued. Holzinger et al. (2002) speculated that the self-activation of trypsinogen and the activation by trypsin independently of enterokinase activity may suffice for protein digestion in the human adult but not in the human infant, given the infant's relatively higher demand for protein digestion.
The transmission pattern of enterokinase deficiency in the families studied by Holzinger et al. (2002) was consistent with autosomal recessive inheritance.
In the families with enterokinase deficiency described by Haworth et al. (1971, 1975), Holzinger et al. (2002) identified compound heterozygous mutations in the PRSS7 gene (606635.0001-606635.0004).
All animals need to digest exogenous macromolecules without destroying similar endogenous constituents. The regulation of digestive enzymes is, therefore, a fundamental requirement. Vertebrates have solved this problem, in part, by using a 2-step enzymatic cascade to convert pancreatic zymogens to active enzymes in the lumen of the gut. The basic features of this cascade were described in 1899 by Schepovalnikov, working in the laboratory of Pavlov (1902). Extracts of the proximal small intestine were shown strikingly to activate the latent hydrolytic enzymes in pancreatic fluid. Pavlov (1902) considered this intestinal factor to be an enzyme that activated other enzymes, or a 'ferment of ferments' and named it enterokinase. The importance of this protease cascade is emphasized by the life-threatening intestinal malabsorption that accompanies congenital deficiency of enterokinase.
Follett, G. F., MacDonald, T. H. Intestinal enterokinase deficiency. Acta Paediat. Scand. 65: 653-655, 1976. [PubMed: 961414] [Full Text: https://doi.org/10.1111/j.1651-2227.1976.tb04948.x]
Ghishan, F. K., Lee, P. C., Lebenthal, E., Johnson, P., Bradley, C. A., Greene, H. L. Isolated congenital enterokinase deficiency: recent findings and review of the literature. Gastroenterology 85: 727-731, 1983. [PubMed: 6347801]
Hadorn, B., Tarlow, M. J., Lloyd, J. K., Wolff, O. H. Intestinal enterokinase deficiency. Lancet 293: 812-813, 1969. Note: Originally Volume I. [PubMed: 4180366] [Full Text: https://doi.org/10.1016/s0140-6736(69)92071-6]
Haworth, J. C., Gourley, B., Hadorn, B., Sumida, C. Malabsorption and growth failure due to intestinal enterokinase deficiency. J. Pediat. 78: 481-490, 1971. [PubMed: 4322674] [Full Text: https://doi.org/10.1016/s0022-3476(71)80231-7]
Haworth, J. C., Hadorn, B., Gourley, B., Prasad, A., Troesch, V. Intestinal enterokinase deficiency: occurrence in two sibs and age dependency of clinical expression. Arch. Dis. Child. 50: 277-282, 1975. [PubMed: 1147667] [Full Text: https://doi.org/10.1136/adc.50.4.277]
Holzinger, A., Maier, E. M., Buck, C., Mayerhofer, P. U., Kappler, M., Haworth, J. C., Moroz, S. P., Hadorn, H.-B., Sadler, J. E., Roscher, A. A. Mutations in the proenteropeptidase gene are the molecular cause of congenital enteropeptidase deficiency. Am. J. Hum. Genet. 70: 20-25, 2002. [PubMed: 11719902] [Full Text: https://doi.org/10.1086/338456]
Lebenthal, E., Antonowicz, I., Shwachman, H. Enterokinase and trypsin activities in pancreatic insufficiency and diseases of the small intestine. Gastroenterology 70: 508-512, 1976. [PubMed: 943355]
Lentze, M. J., Green, J. R., Sterchi, E. E., Nussle, D., Hermier, M. Intestinal enteropeptidase deficiency associated with exocrine pancreatic insufficiency. (Letter) Lancet 320: 504 only, 1982. Note: Originally Volume II. [PubMed: 6125673] [Full Text: https://doi.org/10.1016/s0140-6736(82)90538-4]
Moroz, S. P., Hadorn, B., Rossi, T. M., Haworth, J. C. Celiac disease in a patient with a congenital deficiency of intestinal enteropeptidase. Am. J. Gastroent. 96: 2251-2254, 2001. [PubMed: 11467662] [Full Text: https://doi.org/10.1111/j.1572-0241.2001.03970.x]
Pavlov, J. P. The Work of the Digestive Glands. (1st ed.) London: Charles Griffin (pub.) 1902.
Tarlow, M. J., Hadorn, B., Arthurton, M. W., Lloyd, J. K. Intestinal enterokinase deficiency: a newly-recognized disorder of protein digestion. Arch. Dis. Child. 45: 651-655, 1970. [PubMed: 5477679] [Full Text: https://doi.org/10.1136/adc.45.243.651]