Ruled Out: Neurotransmitter Disease & More

I'd like to start with an important tip for any patient or parent thereof: be aware of your lab work. It is vital to know the following about labs:

1. When is the sample collected? (This is frequently used in the identifier like: 4/20/09 AFP.)
   
2. When is the sample sent out? (Many labs can't send out after 3PM so it may be next day.)
3. When is the sample received? (Usually the day after it is *sent*, but not always. Fresh samples may have to get there within 2 hours otherwise it is void. Other things, such as clotting and contamination can also void the test--and they won't always tell you!)
4. What is the substance? (plasma, red blood cells, white blood cells, cerebrospinal fluid, urine, tissue, etc.)
5. What lab is it being sent to? (Essential for follow-up. Don't trust your send-out lab.)
   
6. What is the turnaround time? (If weeks, do they count business days only? 2 weeks may actually mean closer to 20 days.)

This may sound anal-retentive to a lot of people out there. But, when it's your kid's life on the line, it is not. When a child has an approximately five-year life expectancy, even a few days delay is intolerable. I can't even tell you how many times (safely 10+ times) this knowledge about Bertrand's labs has shaved days or, such as today, weeks of uncertainty in B's case.

Today, after our Primary Childrens Medical Center lab said to give results a few more weeks, I followed up with Medical Neurogenetics, Inc., the Atlanta based laboratory running the neurotransmitter metabolites panel for Bertrand. Turns out that they had already faxed the results back LAST WEEK. The paper was just sitting in a pile somewhere at PCMC waiting to be scanned in--which can take weeks. So, I had the results faxed directly to Dr. Longo.

Dr. Longo being the fabulous clinician (AND researcher) that he is, and in spite of being out of town at a conference, let me know within minutes that the result was normal and that Bertrand's purine panel returned normal again as well. He is now thinking about next steps. (I call Bertrand my man of mystery!) But, the normal neurotransmitter metabolite panel means Bertrand doesn't have a pediatric neurotransmitter disease such as:

• Succinic Semialdehyde Dehydrogenase Deficiency (SSADH)
• Tyrosine Hydroxylase Deficiency (TH)
• Aromatic L-Amino Acid Decarboxylase Deficiency (AADC)
• Guanosine Triphosphate Cyclohydrolase I Deficiency(GCH I, GTP
• Cyclohydrolase, GTPCH)
• Sepiapterin Reductase Deficiency (SR)

As mentioned before, the normal purine panel means no Lesch-Nyhan, but it also rules out quite a few other diseases, such as those listed below in case you are curious.

Disorders of Purine Salvage

• Lesch-Nyhan syndrome
• Adenine phosphoribosyltransferase deficiency

Disorders of Purine Nucleotide Synthesis

• Phosphoribosylpyrophosphate synthetase superactivity
• Adenylosuccinase deficiency

Disorders of Purine Catabolism

• Myoadenylate deaminase deficiency
• Adenosine deaminase deficiency
• Purine nucleoside phosphorylase deficiency
• Xanthine oxidase deficiency

Disorders of Pyrimidine Metabolism

• Uridine monophosphate synthase deficiency

Ruled Out: Mitochondrial Disease (*maybe*)

Calling the lab today to check on the status of Bertrand's 4/14/09 (still not in) I was surprised by what was in: some of today's lab results. Here they are.

• Creatine 173 (normal range <296)
• Cortisol 20.3 (normal range 1-23)
• Glucose 53 (normal range 40-70)
• Lactic Acid 1.0 (normal range 0.8-2.2)

The normal lactic acid doesn't completely rule out the mitochondrials (only with a muscle biopsy could we be sure), but it makes a mitochondrial disease highly unlikely.

The normal creatine makes a peroxisomal disorder unlikely. In particular, the normal cortisol and glucose make Allgrove unlikely as well. (However, another ACTH test is still pending--this could still lead to some symptomatic steroid treatment.)

Lumbar puncture, electromyography, etc.

Bertrand gets ready for his LP & EMG on the hospital bed.

Bertrand had his lumbar puncture (a.k.a. spinal tap) and an impromptu electromyography (EMG) today. While we'll start getting results back tomorrow (such as lactate) for labs run on the cerebrospinal fluid (CSF) tomorrow, we have the EMG results now.

The EMG of his arms/hands and legs/feet confirmed what we learned from the nerve conduction study. Bertrand's peripheral nerves show signs of demylenation. In his arms/hands he has what would be classified in adults as carpal tunnel syndrome. Just like his daddy! (Except in B's case it is not due to the compression of the median nerve, but the demylenation of it).

Based on this and some other information, Dr. Sakonju (B's neurologist) and I discussed a trial course of Valium. Bertrand is currently prescribed Valium in case of seizure only. These smaller doses of Valium would be taken before physical therapy or activity so he could get the most out of it. We'll see.

Bertrand will be seeing Dr. Sakonju again for a follow-up on June 10th. Earlier that day he's scheduled to have a brain CT scan to look for calcifications in the basal ganglia. This may or may not be proceeded with depending on the results of his labs... for now, however, it is a go.

General anesthesia was used today, so Bertrand fortunately didn't have to go through the IV trauma or the blood draw trauma (it took 4 sticks). Some of the blood will be sent out to labs in Georgia and elsewhere, and if we don't get some clear answers within the next 6 weeks or so, a muscle biopsy will take place sometime in July.