SNOMEDCT: 722207000; ORPHA: 199337;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 20q11.21 | Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis | 612714 | Autosomal recessive | 3 | COX4I2 | 607976 |
A number sign (#) is used with this entry because exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis is caused by homozygous mutation in the COX4I2 gene (607976) on chromosome 20q11.
Shteyer et al. (2009) reported 3 brothers from a consanguineous Arab Muslim family with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis. The patients presented with steatorrhea, failure to thrive, and anemia soon after birth. Supplementation with pancreatic enzymes improved the steatorrhea, but growth was not normal until about 4 years of age. Red blood cell transfusions improved the anemia in 2 patients, but not in the third, who developed hepatosplenomegaly and episodic jaundice associated with mild indirect hyperbilirubinemia. He also improved by 4 years of age. All 3 brothers had a large, box-shaped skull with a bony groove between the frontal and occipital fontanelles. Other features included a localized scaly skin rash over the perineum, small hyperpigmented lesions, bronchial asthma, maldentition, and severe dental caries. A skeletal survey showed delayed bone age and osteopenia. Two girls from another consanguineous Arab Muslim family had a similar disorder with slightly variable features. One girl had failure to thrive, pancreatic exocrine insufficiency, and anemia, but not calvarial hyperostosis or skin rash. She had had delayed psychomotor development, which improved with pancreatic enzyme supplementation. The other girl had anemia, hepatosplenomegaly, a box-shaped skull, and failure to thrive, but her stools were of normal consistency with no evidence of a coagulopathy. CT scan showed pancreatic atrophy with massive fatty infiltration. She also had allergic rhinitis and severe asthma and was easily fatigued. Speech and comprehension were age appropriate, but she was doing poorly at school. Two additional infants from this family had died with severe jaundice, anemia, and hepatosplenomegaly. Bone marrow biopsies from all affected individuals showed erythroid hyperplasia with megaloblastic change and bi- and multi-nucleated red cell precursors, consistent with dyserythropoietic anemia. Glucose-tolerance tests were normal.
In 5 affected individuals from 2 Arab Muslim families with pancreatic exocrine insufficiency, dyserythropoietic anemia, and calvarial hyperostosis, Shteyer et al. (2009) identified a homozygous mutation in the COX4I2 gene (607976.0001).
Shteyer, E., Saada, A., Shaag, A., Al-Hijawi, F. A., Kidess, R., Revel-Vilk, S., Elpeleg, O. Exocrine pancreatic insufficiency, dyserythropoeitic (sic) anemia, and calvarial hyperostosis are caused by a mutation in the COX4I2 gene. Am. J. Hum. Genet. 84: 412-417, 2009. [PubMed: 19268275] [Full Text: https://doi.org/10.1016/j.ajhg.2009.02.006]