 Celestine Gregerson is next. She is actually one of our U of U students here today, so some time over to her. I'm excited to be speaking this morning on this interesting case that was seen here in pediatric ophthalmology clinic. This patient initially presented in 2017. She was two months old at the time. She was referred to us by an outside pediatric ophthalmologist who was requesting a second opinion on a possible cataract in the right eye. Past medical history was non-contributory. She was born at term, VSC section, no complications. Mom had hypertension and gestational diabetes during pregnancy. There was no family history of congenital cataracts and mom had reported that the patient was behaving normally up until this point. On exam, bilateral cataracts were seen. Shown here you can see the posterior, there's posterior vacuolite collections that on the right side are located peripherally and encroaching somewhat centrally, and then on the left side they're located peripherally. The retinoscopic reflux was not distorted in either eye, and interestingly enough, there was a surprisingly high amount of myopia found in both eyes of about minus five. Exam was otherwise unremarkable. The idea of lab testing at this time was considered, but given the lack of retinoscopic reflux distortion, it was decided to just watch closely. So taking a brief moment here to consider the differential diagnosis for bilateral congenital cataracts, which is quite broad. In our patient, we were considering non-syndromic and syndromic genetic causes, also metabolic causes. Congenital infection was on our differential and then also, given the posterior location, a pre-existing posterior capsular defect was possible. Three weeks later, the patient returned and the cataracts, as you can see, had progressed bilaterally. Lab work was ordered at this time, including a BMP, calcium, phosphorus, red-silk lactose 1-phosphate, and congenital workup. Some of the results are shown here. They were significant for an elevation in lactose 1-phosphate and elevation in Hsv and rabilititis. Given this elevation in lactose 1-phosphate, the geneticists that was helping us on this case recommended that we pursue further testing for galactokinase deficiency and galactosemia. Just a brief biochemistry refresher. Lactose, which is taken in through our diet, is broken down into glucose and galactose, and then galactose is metabolized via this pathway. These two enzymes, galtengoc, are the ones that are implicated in galactosemia and galactokinase deficiency. Galt is the one that is deficient in galactosemia, and then galactokinase acts here. Deficiencies in either enzyme can result in an accumulation of galactose, which is then reduced to galactosol, which deposits in the cataract or in the lenses. The decision was actually at this time, kind of considering this pathway, we discussed the possibility with mom of trying to eliminate milk from the patient's diet. Mom was interested in this option, so she decided to switch the patient to a completely soy based formula. Two weeks on this formula, you can see there's actually regression in the cataract, especially in the right eye. However, the patient actually tested negative for galactoskinase deficiency and galactosemia, which is a little bit of a puzzle. The option to discontinue soy formula was discussed at this time. But mom was encouraged by the regression in the right cataract, so she decided to continue soy formula. And the patient was scheduled to see geneticists and for further genetic testing a few months out. Meanwhile, she continued to fall up with us. And in the following images, you can see the change in her cataracts that occurred in the following year and a half. So here, actually, I don't know if you can appreciate that on the right side, the cataract did regress mildly. Left side remained stable. And then this was earlier this year. Here's a side by side comparison. This idea of reversible cataracts has actually been pretty rarely described. In galactosemia and galactokinase deficiency, you can sometimes see regression cataracts if lactose is eliminated from the diet early on. Patients with galactosemia typically have this oil droplet cataract with posterior lenticonus, which our patient didn't have. And so we were interested to see the results of the genetic testing. She tested positive for pathogenic variant of the MAF gene. And now MAF is a transcription factor that has a lot of different functions, but it's embryonicly it functions to help with lens fiber cell development. And it is associated with congenital cataracts. And it's also associated with the syndrome army group syndrome. So our patient actually received a tentative diagnosis of army group syndrome. This syndrome is a rare autosomal dominant syndrome that is as a prevalence worldwide of about less than one in a million. It has this clinically homogenous phenotype that is outlined here. And as you can see it manifests systemically. The cataracts in this syndrome have not previously been described as reversible. And typically the cataracts are actually a posterior oil droplet cataract with posterior lenticonus, similar to the galactocinase or galactosemia cataract. So on further investigation, our patient was actually found to be heterogeneous for a for a complete lesion, expanding the entire coding sequence for the MAF protein. This is in contrast to the single nucleotide variants that are exclusively described in or I should say in army group syndrome is they exclusively described to have the single nucleotide variants. And of course, the cataract that I showed you earlier in our patient was quite different from the characteristic cataract of army group syndrome. Additionally, our patient as she continued to develop did not have any of these physical characteristics. And she was meeting milestones. So really didn't match the army group syndrome diagnosis. So we have this kind of dichotomy between clinical phenotype and genotype. Given the lack of syndromic features in our patients, it's possible that a deletion of the complete coding sequence of the MAF protein is actually less damaging than a mis-sense mutation that you would have in army group syndrome. And perhaps the mis-sense mutation has kind of a dominant negative effect in army group syndrome. So just a few points to consider this case actually remains a little bit of a mystery. If we're to kind of focus follow on Occam's razor approach, the cataract progressed with milk elimination, we could assume that this was the galactokinase efficiency, and maybe an atypical presentation. But something to remember is that we don't know for certain that there's actually a causation or even a correlation relationship, it's possible that this was just the coincidence and timing and the cataract sort of reversed on their own anyways. In recent years, we've seen this transition from predominantly infectious work up to a genetic work of and that poses some challenges because as you can see illustrated in this case, sometimes what do we do when the genotype doesn't actually fit the clinical picture? And then also what do we do with the genetic information that we gain, such as a complete deletion of the coding sequence of the MAF protein, that we don't really know what the significance is. So that's another question that we want to consider. And then I think this case also begs the question, should we be doing genetic testing for isolated congenital cataracts? The study that I've cited here at the bottom in Australia, they found that in pediatric patients that didn't have any syndromic features, it actually was very unhelpful to perform this genetic testing because their pre-test probability was already so low. And so with that, I want to thank you all for your attention and your time and thank these individuals for the help with my presentation.