Entry - #261500 - EOSINOPHIL PEROXIDASE DEFICIENCY; EPXD - OMIM - (MIRROR)
# 261500

EOSINOPHIL PEROXIDASE DEFICIENCY; EPXD


Alternative titles; symbols

EOSINOPHIL PEROXIDASE DEFICIENCY, PARTIAL
PEROXIDASE AND PHOSPHOLIPID DEFICIENCY IN EOSINOPHILS
PRESENTEY ANOMALY


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
17q22 [Eosinophil peroxidase deficiency] 261500 AR 3 EPX 131399
Clinical Synopsis
 

INHERITANCE
- Autosomal recessive
LABORATORY ABNORMALITIES
- Decreased or absent peroxidase activity
- Decreased volume of the granule matrix
- Eosinophil nuclear hypersegmentation, hypogranulation, and negative peroxidase and phospholipid staining
- Increase in the ratio between the size of the matrix and the core of the specific granules seen on EM
MISCELLANEOUS
- No clinical manifestations
MOLECULAR BASIS
- Caused by mutation in the eosinophil peroxidase gene (EPX, 131399.0001)

TEXT

A number sign (#) is used with this entry because of evidence that eosinophil peroxidase deficiency (EXPD) is caused by homozygous or compound heterozygous mutation in the EPX gene (131399) on chromosome 17q22.


Description

Eosinophil peroxidase deficiency is a rare abnormality of eosinophil granulocytes characterized by decreased or absent peroxidase activity and decreased volume of the granule matrix (summary by Romano et al., 1994). Nakagawa et al. (2001) noted that there are no clinical symptoms and the diagnosis is made solely by cytochemical analysis.


Clinical Features

In Yemenite Jews in Israel, Presentey (1969) and Presentey and Szapiro (1969) described a 'new' anomaly of eosinophils characterized by nuclear hypersegmentation, hypogranulation, and negative peroxidase and phospholipid staining.

Lepelley et al. (1987) described the Presentey anomaly in twin sisters; one had refractory anemia, which may have been coincidental and merely the symptom that brought the twins to attention.

In contrast to myeloperoxidase deficiency (254600), in which all neutrophils and monocytes are affected, isolated deficiency of eosinophil peroxidase is very rare (Presentey (1970, 1984); Presentey and Joshua, 1982; Schaeffer et al., 1977).

Hoffmann and Tielens (1987) reported the case of an affected 4-year-old boy of Turkish ancestry whose parents were 'consanguineous in the second degree.' Hoffmann and Tielens (1987) commented on the fact that the use of automated flow-cytochemical analyzers in the hematology laboratory had stimulated interest in peroxidase activity of granulocytes and brought many cases of hereditary and acquired deficiency to attention. It was in this way that their case was detected. Valdes and Calero (1987) described a patient with deficiency of eosinophil peroxidase detected by flow cytochemistry.

Electron microscopic analyses of peroxidase-deficient eosinophils showed an increase in the ratio between the size of the matrix and the core of the specific granules (Lepelley et al., 1987; Lejeune et al., 1988). Zabucchi et al. (1992) found 5 eosinophil peroxidase-deficient subjects among 131,000 peripheral blood samples examined by routine automated methods. All met the main criteria: absent or strongly decreased reaction for peroxidase, absent or strongly decreased staining with Sudan Black, and an increased ratio of the granule core volume to the total granule volume. Zabucchi et al. (1992) demonstrated that the increased core-matrix ratio was caused mainly by a decrease of the volume of the matrix and that 2 other matrix proteins, eosinophil cationic protein (131398) and eosinophil-derived neurotoxin (131410), appeared to be present in normal amounts.

Nakagawa et al. (2001) reported a 62-year-old man who was found to have EPO deficiency during routine peripheral blood testing for investigation of colon polyps; he had no history of recurrent infection or allergy.


Inheritance

In the patients with eosinophil peroxidase deficiency reported by Presentey (1969) and Presentey and Szapiro (1969), recessive inheritance seemed quite clear.


Molecular Genetics

In a man with eosinophil peroxidase deficiency, Romano et al. (1994) identified compound heterozygosity for mutations in the EPX gene (131399.0001-131399.0002).

In a man with eosinophil peroxidase deficiency, Nakagawa et al. (2001) identified homozygosity for a mutation in the EPX gene (131399.0003). His wife carried homozygous wildtype alleles, whereas his son and daughter were heterozygous for the mutation. Cytochemical blood analysis in his children showed a completely normal display.


REFERENCES

  1. Hoffmann, J. J., Tielens, A. G. Partial deficiency of eosinophil peroxidase. Blut 54: 165-169, 1987. [PubMed: 3814833, related citations] [Full Text]

  2. Lejeune, F., Dournovo, M., Turpin, F., Saula, H., Lortholary, P. Deficit en peroxidase des eosinophiles: etude cytologique en microscopie optique et electronique a propos d'un cas. Nouv. Rev. Franc. Hemat. 30: 177-182, 1988. [PubMed: 3419898, related citations]

  3. Lepelley, P., Zandecki, M., Parquet, S., Lerche, B., Estienne, M. H., Fenaux, P., Torpier, G., Cosson, A. Total peroxidase deficiency in eosinophils: a report on twin sisters, one with a refractory anaemia. Europ. J. Haemat. 39: 77-81, 1987. [PubMed: 2820788, related citations] [Full Text]

  4. Nakagawa, T., Ikemoto, T., Takeuchi, T., Tanaka, K., Tanigawa, N., Yamamoto, D., Shimizu, A. Eosinophilic peroxidase deficiency: identification of a point mutation (D648N) and prediction of structural changes. (Abstract) Hum. Mutat. 17: 235-236, 2001. Note: Full article online.

  5. Presentey, B., Joshua, H. Peroxidase and phospholipid deficiency in human eosinophilic granulocytes: a marker in population genetics. Experientia 38: 628-629, 1982. [PubMed: 6178618, related citations] [Full Text]

  6. Presentey, B. Z., Szapiro, L. Hereditary deficiency of peroxidase and phospholipids in eosinophilic granulocytes. Acta Haemat. 41: 359-362, 1969. [PubMed: 4982578, related citations] [Full Text]

  7. Presentey, B. Z. Morphologic observations and genetic follow-up of a familial anomaly of eosinophils. Am. J. Clin. Path. 51: 458-462, 1969. [PubMed: 5774660, related citations] [Full Text]

  8. Presentey, B. Partial and severe peroxidase and phospholipid deficiency in eosinophils: cytochemical and genetic considerations. Acta Haemat. 44: 345-354, 1970. [PubMed: 4996389, related citations] [Full Text]

  9. Presentey, B. Ultrastructure of human eosinophils genetically lacking peroxidase. Acta Haemat. 71: 334-340, 1984. [PubMed: 6429999, related citations] [Full Text]

  10. Romano, M., Patriarca, P., Melo, C., Baralle, F. E., Dri, P. Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic studies and evidence for a compound heterozygosity of the defect. Proc. Nat. Acad. Sci. 91: 12496-12500, 1994. [PubMed: 7809065, related citations] [Full Text]

  11. Schaeffer, H. E., Hellriegel, K. P., Fischer, R. Zytochemischer Nachweis der Eosinophilen-Peroxidase (EPOX) unter besonderer Berucksichtigung des isolierten Peroxidase-Defektes in Eosinophilen. Acta Histochem. Suppl. XVIII: 195-201, 1977.

  12. Valdes, M. D., Calero, M. A. Deficiency of eosinophil peroxidase detected by automated cytochemistry. Acta Haemat. 78: 265 only, 1987. [PubMed: 3122494, related citations] [Full Text]

  13. Zabucchi, G., Soranzo, M. R., Menegazzi, R., Vecchio, M., Knowles, A., Piccinini, C., Spessotto, P., Patriarca, P. Eosinophil peroxidase deficiency: morphological and immunocytochemical studies of the eosinophil-specific granules. Blood 80: 2903-2910, 1992. [PubMed: 1450416, related citations]


Contributors:
Carol A. Bocchini - updated : 8/18/2015
Creation Date:
Victor A. McKusick : 6/4/1986
carol : 03/17/2022
carol : 08/18/2015
carol : 11/13/2013
carol : 11/12/2013
carol : 1/13/1995
terry : 4/18/1994
mimadm : 3/29/1994
warfield : 3/22/1994
carol : 2/11/1993
carol : 1/28/1993

# 261500

EOSINOPHIL PEROXIDASE DEFICIENCY; EPXD


Alternative titles; symbols

EOSINOPHIL PEROXIDASE DEFICIENCY, PARTIAL
PEROXIDASE AND PHOSPHOLIPID DEFICIENCY IN EOSINOPHILS
PRESENTEY ANOMALY


SNOMEDCT: 711160007;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
17q22 [Eosinophil peroxidase deficiency] 261500 Autosomal recessive 3 EPX 131399

TEXT

A number sign (#) is used with this entry because of evidence that eosinophil peroxidase deficiency (EXPD) is caused by homozygous or compound heterozygous mutation in the EPX gene (131399) on chromosome 17q22.


Description

Eosinophil peroxidase deficiency is a rare abnormality of eosinophil granulocytes characterized by decreased or absent peroxidase activity and decreased volume of the granule matrix (summary by Romano et al., 1994). Nakagawa et al. (2001) noted that there are no clinical symptoms and the diagnosis is made solely by cytochemical analysis.


Clinical Features

In Yemenite Jews in Israel, Presentey (1969) and Presentey and Szapiro (1969) described a 'new' anomaly of eosinophils characterized by nuclear hypersegmentation, hypogranulation, and negative peroxidase and phospholipid staining.

Lepelley et al. (1987) described the Presentey anomaly in twin sisters; one had refractory anemia, which may have been coincidental and merely the symptom that brought the twins to attention.

In contrast to myeloperoxidase deficiency (254600), in which all neutrophils and monocytes are affected, isolated deficiency of eosinophil peroxidase is very rare (Presentey (1970, 1984); Presentey and Joshua, 1982; Schaeffer et al., 1977).

Hoffmann and Tielens (1987) reported the case of an affected 4-year-old boy of Turkish ancestry whose parents were 'consanguineous in the second degree.' Hoffmann and Tielens (1987) commented on the fact that the use of automated flow-cytochemical analyzers in the hematology laboratory had stimulated interest in peroxidase activity of granulocytes and brought many cases of hereditary and acquired deficiency to attention. It was in this way that their case was detected. Valdes and Calero (1987) described a patient with deficiency of eosinophil peroxidase detected by flow cytochemistry.

Electron microscopic analyses of peroxidase-deficient eosinophils showed an increase in the ratio between the size of the matrix and the core of the specific granules (Lepelley et al., 1987; Lejeune et al., 1988). Zabucchi et al. (1992) found 5 eosinophil peroxidase-deficient subjects among 131,000 peripheral blood samples examined by routine automated methods. All met the main criteria: absent or strongly decreased reaction for peroxidase, absent or strongly decreased staining with Sudan Black, and an increased ratio of the granule core volume to the total granule volume. Zabucchi et al. (1992) demonstrated that the increased core-matrix ratio was caused mainly by a decrease of the volume of the matrix and that 2 other matrix proteins, eosinophil cationic protein (131398) and eosinophil-derived neurotoxin (131410), appeared to be present in normal amounts.

Nakagawa et al. (2001) reported a 62-year-old man who was found to have EPO deficiency during routine peripheral blood testing for investigation of colon polyps; he had no history of recurrent infection or allergy.


Inheritance

In the patients with eosinophil peroxidase deficiency reported by Presentey (1969) and Presentey and Szapiro (1969), recessive inheritance seemed quite clear.


Molecular Genetics

In a man with eosinophil peroxidase deficiency, Romano et al. (1994) identified compound heterozygosity for mutations in the EPX gene (131399.0001-131399.0002).

In a man with eosinophil peroxidase deficiency, Nakagawa et al. (2001) identified homozygosity for a mutation in the EPX gene (131399.0003). His wife carried homozygous wildtype alleles, whereas his son and daughter were heterozygous for the mutation. Cytochemical blood analysis in his children showed a completely normal display.


REFERENCES

  1. Hoffmann, J. J., Tielens, A. G. Partial deficiency of eosinophil peroxidase. Blut 54: 165-169, 1987. [PubMed: 3814833] [Full Text: https://doi.org/10.1007/BF00320371]

  2. Lejeune, F., Dournovo, M., Turpin, F., Saula, H., Lortholary, P. Deficit en peroxidase des eosinophiles: etude cytologique en microscopie optique et electronique a propos d'un cas. Nouv. Rev. Franc. Hemat. 30: 177-182, 1988. [PubMed: 3419898]

  3. Lepelley, P., Zandecki, M., Parquet, S., Lerche, B., Estienne, M. H., Fenaux, P., Torpier, G., Cosson, A. Total peroxidase deficiency in eosinophils: a report on twin sisters, one with a refractory anaemia. Europ. J. Haemat. 39: 77-81, 1987. [PubMed: 2820788] [Full Text: https://doi.org/10.1111/j.1600-0609.1987.tb00169.x]

  4. Nakagawa, T., Ikemoto, T., Takeuchi, T., Tanaka, K., Tanigawa, N., Yamamoto, D., Shimizu, A. Eosinophilic peroxidase deficiency: identification of a point mutation (D648N) and prediction of structural changes. (Abstract) Hum. Mutat. 17: 235-236, 2001. Note: Full article online.

  5. Presentey, B., Joshua, H. Peroxidase and phospholipid deficiency in human eosinophilic granulocytes: a marker in population genetics. Experientia 38: 628-629, 1982. [PubMed: 6178618] [Full Text: https://doi.org/10.1007/BF02327088]

  6. Presentey, B. Z., Szapiro, L. Hereditary deficiency of peroxidase and phospholipids in eosinophilic granulocytes. Acta Haemat. 41: 359-362, 1969. [PubMed: 4982578] [Full Text: https://doi.org/10.1159/000208873]

  7. Presentey, B. Z. Morphologic observations and genetic follow-up of a familial anomaly of eosinophils. Am. J. Clin. Path. 51: 458-462, 1969. [PubMed: 5774660] [Full Text: https://doi.org/10.1093/ajcp/51.4.458]

  8. Presentey, B. Partial and severe peroxidase and phospholipid deficiency in eosinophils: cytochemical and genetic considerations. Acta Haemat. 44: 345-354, 1970. [PubMed: 4996389] [Full Text: https://doi.org/10.1159/000208703]

  9. Presentey, B. Ultrastructure of human eosinophils genetically lacking peroxidase. Acta Haemat. 71: 334-340, 1984. [PubMed: 6429999] [Full Text: https://doi.org/10.1159/000206611]

  10. Romano, M., Patriarca, P., Melo, C., Baralle, F. E., Dri, P. Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic studies and evidence for a compound heterozygosity of the defect. Proc. Nat. Acad. Sci. 91: 12496-12500, 1994. [PubMed: 7809065] [Full Text: https://doi.org/10.1073/pnas.91.26.12496]

  11. Schaeffer, H. E., Hellriegel, K. P., Fischer, R. Zytochemischer Nachweis der Eosinophilen-Peroxidase (EPOX) unter besonderer Berucksichtigung des isolierten Peroxidase-Defektes in Eosinophilen. Acta Histochem. Suppl. XVIII: 195-201, 1977.

  12. Valdes, M. D., Calero, M. A. Deficiency of eosinophil peroxidase detected by automated cytochemistry. Acta Haemat. 78: 265 only, 1987. [PubMed: 3122494] [Full Text: https://doi.org/10.1159/000205890]

  13. Zabucchi, G., Soranzo, M. R., Menegazzi, R., Vecchio, M., Knowles, A., Piccinini, C., Spessotto, P., Patriarca, P. Eosinophil peroxidase deficiency: morphological and immunocytochemical studies of the eosinophil-specific granules. Blood 80: 2903-2910, 1992. [PubMed: 1450416]


Contributors:
Carol A. Bocchini - updated : 8/18/2015

Creation Date:
Victor A. McKusick : 6/4/1986

Edit History:
carol : 03/17/2022
carol : 08/18/2015
carol : 11/13/2013
carol : 11/12/2013
carol : 1/13/1995
terry : 4/18/1994
mimadm : 3/29/1994
warfield : 3/22/1994
carol : 2/11/1993
carol : 1/28/1993