Since the pathophysiological features of the two diseases are virtually identical, NKCE and LG are now commonly viewed as manifestations of the same disease.Only 36 patients with NKCE or LG have been reported as of January 2019. Nonetheless, these diseases are emerging as important clinical entities because they 1) are newly described and likely to be diagnosed more often as they become better known and 2) have been mistaken for, and treated as, various types of pre-malignant and malignant lymphomas of the GI tract. Given the radical differences in the prognoses and treatments of NKCE and LG compared to the lymphomas that they can mimic, the evaluation of many lymphocyte-proliferating disorders of the GI tract must consider and rule out the possibility that they are NKCE or LG rather than a pre-malignant disorder or malignant lymphoma. Presentation
Most cases of NKCE and LG have been reported in middle-aged or older individuals. Patients diagnosed with NKCE (medium age 46 years) have presented with vague abdominal pain, indigestion, vomiting, diarrhea, constipation, weight loss, anemia, and/or GI bleeding. Two patients complained of biliary colic (i.e. gallbladder pain) and were found to have typical lesions of NKCE in their cystic ducts. These two cases indicate that NKCE involvement is not totally limited to the alimentary canal. Three of 15 individuals diagnosed with NKCE disease reported no symptoms, their disease being found on endoscopy conducted for screening purposes.
General
Most patients continue to grow poorly after birth. Genetics
Typical childhood-onset cerebroretinal microangiopathy with calcifications and cysts is caused by compound heterozygous mutations in the conserved telomere maintenance component 1 (CTC1) gene located in chromosome 17p.31. A late-onset phenotype without abnormal eye findings from a CTC1 mutation has been reported.CTC1 is a component of the CST complex, which is additionally composed of oligonucleotide/oligosaccharide-binding fold containing 1 (coded by OBFC1, also known as STN1) and telomerase capping complex subunit homolog 1 (coded by TEN1). CST complex is evolutionarily conserved. It binds to single-stranded DNA and associates with a fraction of telomeres, potentially protecting them. Pathophysiology
Angiomas and numerous abnormal, small, dilated telangiectatic vessels with thickened, sclerotic and calcified walls have been found in those brain areas which also show calcifications.By analogy to Coats disease, the exudative retinopathy is thought to result from breakdown of the blood-retinal barrier at the level of the vascular endothelial cell, resulting in leakage of blood plasma and lipid. Macrophages then migrate into the retina and subretinal space and digest the lipid. The accumulation of the proteinaceous exudate and macrophages thickens the retina, leading to exudative retinal detachment. Diagnosis
Clinical
The retinal changes are easily identified by ophthalmoscopy, which is performed under general anesthesia if the child is very young. The abnormal vessels are even better seen with fluorescein angiography. In advanced disease, glaucoma is diagnosed by measuring intraocular pressure and cataract by using slit lamp biomicroscopy.