Anyone have any information on any of this???

April 5, 2005

Vicki

I think most of those things are what he does on all of our kids who have seen him. There are some that are specific to Caden probably. I will tell you on the Prader Willi that he tests all his kids on it and also on Retts. I wouldn't get too worked up about Retts since they have only found it in very few boys. They never found it any boy until five years ago or so. The boys that do have it are very very sick and they think many of them don't live outside the womb. I think he just likes to rule this out.

I can't believe he is going to get your results back in 8 weeks...everyone I know had to wait twelve...that's great! The waiting is so hard...I started stalking our mailman! Our report actually came three months to the day...but I was on pins and needles.

We are in the diagnostic game with our new baby so I am going crazy searching online for any nugget that I can figure out...even though it may be a waste of time...it helps pass the time so I don't blame you for digging for info for even the things that seem way out there.

Hang in there!

mom to (07.04.96-05.26.03) with Mitochondrial disease, complex I and IV....Gaige, 5, with High Functioning Autism...Bliss, 3, with very very mild cerebral palsy ...True, born 01.18.05, with GERD and married to one swell man! www.LifeofLoveProject.orgwww.debwells.com

April 5, 2005

I just received Dr. Shoffner's report/notes that lists the things he's looking for in Caden's muscle biopsy. If you have any thoughts or information on any of this, would you please let me know? Does this sound familiar to any of you from your child's biopsy if they had one done??

Mitochondrial Disease: (of course, although he said he thinks it's metabolic) Defects in oxidative phosphorylation can be associated severe global dev. delays as observed in this child. In cases like this one, it is important to also assess fatty acid oxidation. Even if a primary disorder of fatty acid ox. is not identified, patients with mitochondrial defects (particularly complex I defects) will often show secondary defects in fatty acid oxidation. It is important to consider the possibility that this patient could harbor a nuclear mtDNA mutation that is related to clinical presentation. MtDNA mutations can be sporadic or can be segregating at very low levels within other family members making distinctions between nuclear and mito. mechanisms difficult.

Prader Willi Syndrome: Based on the sensitivities of the published criteria, testing is proposed for all newborns/infants with otherwise unexplained hypotonia with poor suck. (Sounds like they test all patients for this one!)

Rett Syndrome mutations (X-linked disorder, typically sporadic) (MECP2 gene mutations in males) Rett syndrome variants are typically regarded as a female disease. However, mutations are being discovered in male patients. male cases have unusual clinical presentations. The clinical manifestations are quite variable and still incompletely understood (GREAT...that's about our luck!) For example, some patients may have features of Angelman syndrome. One male had static encephalopathy, normal head circumference, no seizures, no stereotypical hand movements, and no ataxia. (sounds somewhat like Caden) Mental retardation is common in there males. In most males, muscle weakness, ataxia, abnormal movements like choreoathetosis, normal head circumference (males do not appear to have micocephaly that females demonstrate) and mental retardation are prominent features. (sounds A LOT like Caden)

Cryptic Telomeric Rearrangements: (?? No Idea!) Submicroscopic subtelomeric chromosome defects have been found in 7.4 % of children with moderate to severe mental retardation and in 0.5% of children with mild retardation. Common features (>30%) among subtelomeric deletion cases were microcephaly, short stature, hypertelorism, nasal and ear anomolies, hand anomolies, and cryptorchidism. (doesn't sound like Caden at all)

Congenital Myopathy: Present in early life or infancy with hypotonia and weakness, often with dysmorphic features, relatively non progressive, hereditary, unique morphological features on histochemical or ultrastructural examination of a muscle biopsy.

Cerebral Folate deficiencies: Cerebral folate deficiencies have a variety of causes. The symptoms are complex and include seizures, irritability, ataxia, spastic paraplegia, dyskinesias, and epilepsy. Deceleration of head growth, vision defects, and hearing loss may occur. Neuroimagining can show periventricular dehyelination (this is how it's typed....should it be deMyelination???), supra- and infratentorial atrophy, or normal findings. (We have the normal findings) Folinic acid treatment can be helpful in these patients.

Tetrahydrobipoterin deficiencies: (should it be tetrahydrobiprotein?) As general information, tetrahydrobioterin (typed that way again...maybe it's correct) deficiencies (BH4) are heterogeneous disorders associated with defects in involving BH4 biosynthesis or regeneration. Further assessment is important to delineate one of these disorders is present and whether treatment with BH4 (2-10mg/kg/day) or diet as well as replacement therapy with neurotransmitter precursors (L-dopa, 5-hydroxytryptophan, folinic acid) will be beneficial to this patient. BH4 deficiency comprises a heterogeneous group of autosomal recessive disorders caused by mutations in the PTS (most common), SPR, QHPR, and GCH1 genes. Defects in the SPR gene cause neurotransmitter deficiency without hyperphenylalaniemia; defects in the GTPCH gene (ie, GCH1) may also cause autosomal dominant dopa-responsive dystonia (DRD). Affected children develop progressive developmental delay and neurologic impairment that manifests as psychomotor retardation, progressive neurologic deterioration, convulsions, abnormal movements, hypersalivation, and swallowing difficulties. (he said he doesn't think Caden's is progressive??)

Finally, these are the studies recommended:

1. Muscle biopsy: histochemistry

Immunohistochemistry for oxidative phosphorylation subunit testing

Isolation of mitochondria: Oxidative phosphorylation testing on mitochondria isolated from fresh tissue.

2. Genetic Testing:

MtDNA Southern blot

Point mutations screen: 3243, 3271, 8344, 8993

If testing in muscle is negative for common mutations and OXPHOS enzymology is abnormal, we will proceed with mtDNA testing.

Chromosome microarray analysis

MECP2 gene sequencing

Prader Willi

Myotonic dystrophy, Type 1

3. Metabolic testing:

blood and urine amino acids to screen for metabolic abnormalities that would support the presence of an oxidative phosphorylation disease.

Urine organic acids

blood (plasma) acylcarnitine profile (fast atom bombardment-sent to Duke, Dr. Millington) Anyone heard of him???

blood lactate and pyruvate

blood L-carnitine quantitation (total, free, esterified)

7 dehydrocholesterol

CSF amino acids, lactate, pyruvate

CSF chemistries (protein, glucose, cell count)

CSF neurotransmitter metabolities, neopterin, tetrahydrobiopterin, 5-methyltetrahydrofolate, succinylpurine (To Dr. Hyland via CHOA) Heard of him???

Cell culture based testing:

skin for fibroblast culture

send fibroblasts to Dr. Millington for fatty oxidation testing

Whewwwwww, that's it. If you got this far and know anything about any of this, PLEASE fill me in!! I was pretty okay waiting for these results, but this report really has made me antsy!! It's been 3 weeks. (tomorrow) Only 5 more to go! Thanks ahead of time!

Vicki ~ mom to Caden (10/08/03)**the light of our lives**severe hypotonia, global developmental delays,choreoathetosis, possible metabolic disorder???,lots of other issues.....................AND the cutest face you've ever seen!!!http://www3.caringbridge.org/tx/cadenlane/