Medical Journey to NPC Diagnosis
She's so small. That was my first thought when I first saw Marian, like a miniature porcelain doll.
At Marian's early well baby visits her weight gain left something to be desired. It took her several weeks to hit 7 pounds and at Thanksgiving, when she was three months old, she only weighed 8 pounds.
Marian on Thanksgiving weekend, weighing in at 8 lbs
At Marian's 6 month visit she wasn't sitting up. The doctor pulled her from laying down to sitting and her head lag was appropriate. When tipped Marian knew to put her arm down to support herself, but she had almost no core strength. Marian did impress by saying a garbled "hi" to the doctor at this visit which was exciting. Her weight percentile was low, in the 3 - 5th% range and she also wouldn't bear any weight on her legs.
At 8 months I called our pediatrician as Marian still wasn't bearing weight on her legs or sitting steadily, she also was having trouble transitioning to solid foods. With her support I called Regional Center. The physical therapist evaluator right away said Marian has hypotonia or low muscle tone - something we'd noticed since birth but hadn't known what to call. It's not a condition but a symptom of an underlying problem - ranging from harmless to very serious, often the cause is unknown and not significant. I remembered a video of myself in ice skating lessons with my legs wobbling like overcooked spaghetti. It must run in the family I thought, relieved. She recommended we talk to our pediatrician about whether to see a neurologist.
Around eight months old, Marian used her hands and arms to provide extra support to compensate for weakness. You can also see Marian's enlarged belly from her spleen, although we didn't recognize it at the time
Marian was 9 months and could sit for just a minute before toppling over, note the pillow
At this time our beloved pediatrician retired and we had to quickly pick a new pediatrician and make it a good one. We met our new saving grace pediatrician for the 9 month visit. She took one look at Marian and said she has a sweet spirit, which of course she does. Very insightful right off the bat. She wasn't overly concerned about Marian, but did agree she has "mild to moderate" hypotonia and she could see a neurologist as "an aggressive move," just to make sure. I agreed. She also ordered a slew of labs including a liver panel, CBC, thyroid, lead, etc.
The next week, around May, we went to the neurologist, Dr. A, for the first time. I was sick with worry about what she would say. She was overall reassuring but was clear there were many many things that could be causing this, some harmless, some not so harmless. She ordered a CK test (more labs) and said she'd see Marian monthly. If after a few months she wasn't improving she'd order a MRI. I started my question routine. Are there signs of anything degenerative? Nothing that jumps out right now. She recommended Marian start PT right away, as much as possible.
We called a PT clinic through insurance and were told it would be a three month wait for services. In the interim of waiting for Regional Center, we paid privately for physical therapy twice a week.
Starting physical therapy with Katie at PEAK Physical Therapy at 9 and a half months, Marian didn't bear weight on her legs and couldn't lift her hips off the ground
A few days later we got the test results (ok I obsessively called the office every day) with Marian's CK level: it was low. This was good in the sense that it wasn't high as that would have been a strong indicator for one of the muscular dystrophies. But low CK levels are unusual and doctors generally agree it can point to a problem with muscle mass and/or strength.
In June, I was thrilled with Marian's progress after starting PT, the doctor not so much. She examined Marian and suggested trying to give her more protein to see if that helps the CK level. She said not to worry about the CK now and it could be a lab error, she reordered the test. The MRI that she had previously said we'd talk about in a few months, well, that one she thought we should order now. Oh yes, and there's one other test a microarray to check the number of chromosomes, might as well order that now, too (this came back normal). I asked my question again, does Marian show signs of anything fatal or degenerative? The answer this time made my stomach drop: we'll have to wait and see what the MRI shows.
In July I went back to the neurologist with Emily and Marian, our trio of chaos, the CK came back low again. I can't even tell you how much Greek yogurt I'd fed Marian to try and bump it up. I tried to get Marian to show off her new skills of bearing weight on her legs and pushing from the ground into a supported sit when I placed my hand on her hip and put pressure. The doctor was encouraging but also referred us to CHLA to see their neuromuscular specialist due to Marian's low CK and slow growth/weight gain. Dr. A said Marian might have a congenital myopathy - a genetic muscle problem, ranging from mild to severe. I asked her, pressing her always, it's in my nature - where do you think Marian will fall? No way to know, her guess would be mild to moderate. Can we rule out something degenerative? No.
After a couple months of PT Marian could push up into a sit, was bearing weight on her legs and could sit steadily for long periods of time without compensation
In August, just before Marian's first birthday, CHLA offered us an appointment with Dr. C, a pediatric neurologist, a few days before her scheduled MRI. Dr. C was like an angel. She took an extremely thorough history and did a lengthy physical examination. I kept jabbering at her about what is wrong, and rattling off Marian's skills, and can we please just rule out something degenerative already? Marian started to fuss and I was juggling soothing Marian, thinking of questions, and processing the information all at once. So, when Dr. C said, "I think I can feel her spleen and liver and I'd like to order an abdominal ultrasound to check this, " I said: ok. Later when I told Paul about this, he asked, but what could cause that? I had no idea. But it was important, for better or worse. Dr. C also wanted to add on an abdominal MRI and MRI of her femurs/legs to check the shape of the bones and muscles. Dr. C said she would call me the same day as the testing with results so we wouldn't be waiting in limbo agony.
To accommodate the lengthier MRI we lost our spot in radiology that was the next week. The nurse practitioner said they recommend doing one longer MRI instead of two shorter ones.
The next week it was time to bring Marian back to Dr. A for her monthly visit. Marian was sick with croup. We had been at the emergency room with her earlier in the week when she couldn't stop coughing for ten to twelve hours. She was fine at home but when I got her to the neurologist, alone of course, she started a terrifying coughing fit in the waiting area. I felt so embarrassed that I'd brought her out and like the world's most horrible mother. The neurologist called us back into her office and over the coughing very calmly said, Marian's spleen and liver being enlarged make sense and there are genetic disorders that effect the brain, liver and muscles. It will be difficult to diagnosis.
On September 14 I brought Marian to CHLA for her abdominal ultrasound. Marian did well with only some crying and lots of coughing as she now had bronchiolitis. Afterwards I headed home with Marian and waited for the results.
Dr. C called about 3:30 p.m., Marian was napping. Marian's spleen was about 11 cm and liver was within normal but at the uppermost limits. What does this indicate? It indicates a storage disorder. Something I'd barely heard of. What does this mean? Some of them are progressive, some aren't. Some are treatable....and some aren't. What was left unsaid, hanging in the air: fatal. More testing needed. I called Paul crying and we read together what the internet has to say about storage disorders, it was very bad - reading that of the lysosomal storage disorders, they were almost all fatal by early school age.
In fact, 95% of storage disorders don't have treatment. NPC is a kind of lysosomal storage disorder. 1 in 8,000 babies are born with a lysosomal storage disorder and they are all fatal without treatment. And only 5% have treatments. The odds were not in our favor.
Later that week we saw our pediatrician who gave us an extra long appointment, I cried in her office. She ordered more tests for Marian, re-testing her liver panel, CBC, and adding CMV and Epstein-Barr which are both viruses that can cause an enlarged spleen. I also asked her to refer us to a GI and geneticist at CHLA which she did right away. I called UCLA and got an appointment with a hematologist, as Marian has thalassemia minor anemia which is from my maternal side of the family and I hoped against hope that could be the cause of the enlarged spleen.
The blood work came back with some hope - the CBC showed a high white blood cell count, the liver enzymes were elevated - but that could be normal from a virus, and she did have CMV - which can cause an enlarged spleen. To make matters even better, we went to see a hematologist at UCLA who could easily start a cult he was so calming, who said the thalassemia wouldn't cause many of Marian's issues - but it could cause an enlarged spleen. Hope.
I took Marian for her blood work ordered by Dr. C, they ran a lysosomal storage panel (which does not include NPC), Spinal Muscular Atrophy, Pompe Disease and a Congenital Myopathy panel. I sat typing these tests into my phone looking for which one to root for: answer, none of them. They're all horrible. At this point I had come across Niemann Pick Type C online and started asking the doctors about the possibility of Marian having it. The literature for NPC says it needs to be diagnosed through a skin biopsy, an invasive test if you're not sure. There's actually a blood test that can diagnose it now, but the literature is in the process of being revised.
I took Marian to a GI in Pasadena while waiting for CHLA to get her in with a friend. I asked: is there anything other than a storage disorder that could be causing her spleen to enlarge? Answer: yes, a mitochondrial problem. I said: is that serious? And the doctor looked at me like he knew I copied my lab partners homework in biology. He skipped a beat and said: yes. He then said but don't look it up. He had good ideas of what to pursue for Marian and ordered more labs to screen for mitochondrial issues. FYI I did look it up and you do not want your child to have a mitochondrial issue.
I took Marian back to the lab for about 6 more blood tests, a urine sample (that's fun) and stool sample. All these tests came back in the normal range.
In the midst of the medical stress Marian continued to make great progress in PT, taking first steps with support here at fourteen months