Re: Apraxia...Dyspraxia...Autism....I am so confused!

[Guest guest]

The only place you can get an actual accurate body burden of mercury

besides the hair testing is from France. This will measure the

porhyrin excretion that will indicate if you are dealing with

toxicities, guarenteed to show the existence of mercury toxicity in

the body.You do not need a physcian to order this for you.

http://www.labbio.net/pages/index_vh_eng.htm

The test is relatively cheap about $130.

TOXICOLOGICAL HIGHLIGHT

Porphyrinurias Induced by Mercury and Other Metals

Bruce A. Fowler

University of land, Toxicology Program, 1450 South Rolling Road,

Baltimore, land 21227

ABSTRACT

The article highlighted in this issue is " Quantitative Evaluation of

Urinary Porphyrins as a Measure of Kidney Mercury Content and Mercury

Body Burden during Prolonged Methylmercury Exposure in Rats " by

D. Pingree, P. Lynne Simmonds, T. Rummel, and

S. Woods.

Biomarkers for toxic agents such as methylmercury are ideally early,

chemical-specific biological responses to exposure of a target cell

population which can be measured in accessible biological matrices

such as blood or urine. Chemical-induced alterations in the heme

biosynthetic pathway are among the those biomarkers of chemical

exposure/toxic cell injury that have proven themselves both useful

and reliable over a number of decades. This pathway, which is

essential for life, produces heme, utilized for a host of

hemoproteins including hemoglobin, the cytochrome P450 family, and

mitochondrial cytochromes. There are a host of biological processes

of direct toxicological interest which are dependent upon the heme

biosynthetic pathway. The heme pathway is also highly sensitive to

inhibition by a number of inorganic agents such as lead, mercury, and

arsenicals as well as organic agents such as the chlorinated benzenes

and alcohol. There is also a high degree of correlation between

excretion of specific porphyrins in the urine and other

ultrastructural/biochemical alterations in organelles, such as the

mitochondrion, which contain a number of enzymes in the heme

biosynthetic pathway (Fowler et al., 1987). This indicates the

utility of porphyrinurias in detecting early stages of cell injury.

As noted below, metal-induced disturbances in this pathway have also

proven useful for examining the interactions between metals under

mixture exposure conditions (Mahaffey et al., 1981, Conner et al.,

1995). Over the years, measurement of lead-induced alterations in

this pathway (e.g., blood delta-aminolevulinic acid dehydratase

activity and measurement of erythrocyte zinc protoporphyrin) were

used in making timely public health screening decisions for both

workers and children exposed to lead-containing dust (Piomelli et

al., 1987). These measurements have permitted physicians to ascertain

that sufficient exposure to lead had occurred to produce a

disturbance in an essential biochemical pathway and that a biological

threshold had been crossed.

The question of variability in individual susceptibility to

alterations in the heme pathway by metals such as lead and mercury,

as a function of the biologically active fraction of these metals,

has remained a problem. The paper by Pingree et al. represents a

major contribution towards addressing this question for a common

organometal toxicant (methylmercury) which is of current public

health concern. It examines the relationship between biological

activity against the renal heme biosynthetic pathway and

intracellular biological availability of CH3Hg+ and Hg2+ as monitored

by sodium 2,3-dimercapto-1-propanesulfonic acid (DMPS) mobilization

from the kidney. The import of these studies in a rodent species is

not trivial for humans, since the heme pathway is highly conserved

across species, and previous studies (- et al., 1995)

have shown similar findings with regard to the observed porphyrinuria

pattern. Methylmercury-induced porphyrinuria of renal origin was

first described in rats (Woods and Fowler, 1977) at dose levels that

did not produce signs of neurological dysfunction in this species.

Subsequent studies in humans exposed to mercury vapor (-

et al., 1995) showed similar findings.

The study by Pingree and colleagues makes a substantial contribution

toward a better understanding of the mechanisms underlying this

unique porphyrinuria pattern. It also contributes to the field of

metal toxicology in several specific areas. First, it defines a

relationship between a biological effect (mercury-specific

porphyrinuria pattern) and a target tissue dose of this element as

measured by the relationship with the DMPS mobilizable fraction. The

high degree of statistical correlation between renal mercury burden

and porphyrin excretion in the urine indicates that the observed

mercury-specific porphyrin excretion pattern may be reliably used as

a noninvasive index of the total renal mercury burden. More

specifically, the porphyrinuria pattern clarifies this relationship

in terms of the biologically active fractions of CH3Hg+ and Hg2+ as

evidenced by the strong statistical relationship between DMPS

chelatable fractions and alterations in the observed porphyrinuria.

It is also extremely valuable to be aware of the dose-related nature

of the porphyrinuria pattern across a wide range of doses, both with

regard to the consistency of the effects and with regard to potential

applicability to a wide range of exposures, such as may be

encountered in human populations. These findings are also important

from the pharmacological perspective since they help to delineate the

fraction of these 2 mercurial species being chelated and hence

provide valuable data on the pharmacological efficacy of this

chelating agent. This is also of basic scientific interest since it

would suggest that DMPS is capable of chelating Hg2+ from the renal

metallothionein pool normally found in rat kidney to bind zinc and

copper. In addition, since the heme biosynthetic pathway is highly

conserved across species, the ability to extrapolate these findings

to man or other species of interest is obvious and is supported by

the findings of - et al. (1995). Finally, it should be

noted that a number of studies in the last 20 years have utilized

specific metal porphyrinuria patterns as biomarkers of exposure to

either a single metal (Woods and Fowler, 1977, 1978) or metal

mixtures (Mahaffey et al., 1981; Conner et al., 1995). It will be of

interest to determine if similar relationships exist between the

biologically active fractions of these elements in their respective

target tissues. It should be clear that the approach taken in the

paper by Pingree et al. could be applied to other metal nephrotoxins

which also produce relatively specific porphyrinuria patterns (e.g.,

for lead, using EDTA or DMSA as chelating test agents and for

arsenicals, using perhaps BAL as a chelating test agent). The point

here is that the approach taken in the paper by Pingree et al. could

have broader applicability to a number of toxic metals, either alone

or as mixture combinations.

In summary, the results of this paper provide further evidence of the

utility of chemical-induced alterations in the heme biosynthetic

pathway as a reliable class of biomarker for delineating both the

total tissue burden of a toxic substance such as methyl mercury and

the intracellular bioavailability of reactive chemical species of

this toxic agent. It should be noted that this approach could also be

applied to evaluating the efficacy of new therapeutic agents such as

chelators or perhaps agents which facilitate the excretion of toxic

metals from the body. It is clear that this highly useful class of

biomarker may have as yet undiscovered applications in delineating

both the total tissue burden of toxic metals such as mercury and the

biologically available fraction of reactive chemical species.

NOTES

For correspondence via fax: (410) 455-6314. E-mail: bfowler@....

REFERENCES

Conner, E. A., Yamauchi, H., and Fowler, B. A. (1995). Alterations in

the heme biosynthetic pathway from III-V semiconductor metal indium

arsenide (InAs). Chem. Biol. Interact. 96, 273–285.[iSI][Medline]

Fowler B. A., Oskarsson, A. and Woods, J. S. (1987). Metal- and

metalloid-induced porphyrinurias: Relationships to cell injury. Ann.

N.Y. Acad. Sci. 514, 172–182.[Medline]

-, D., Maiorino, R. M., Zuniga-, M. Z., Xu, Z.,

Hurlbut, K. M., Junco-Munoz, P., Aposhian, M.M., Dart, R.C.,

Gama, J. H., Echeverria, D., Woods, J. S., and Aposhian, H. V.

(1995). Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for

mercury in humans: II. Urinary mercury, porphyrins and

neurobehavioral changes of dental workers in Monterrey, Mexico. J.

Pharmacol. Exp. Ther. 272, 264–274.[Abstract]

Mahaffey, K. R., Capar, S. G, Gladen, B. C., and Fowler, B. A.

(1981). Concurrent exposure to lead, cadmium and arsenic. Effects on

toxicity and tissue metal concentrations in the rat. J. Lab. Clin.

Med. 98, 463–481.[iSI][Medline]

Piomelli, S., Seaman, C., and Kapoor, S. (1987). Lead-induced

abnormalities in porphyrin metabolism: The relationship with iron

deficiency. Ann. N.Y. Acad. Sci. 514, 278–288.[Medline]

Woods, J. S., and Fowler, B. A. (1977). Renal porphyrinuria during

chronic methyl mercury exposure. J. Lab. Clin. Med. 90, 266–272.[iSI]

[Medline]

Woods, J. S., and Fowler, B. A. (1978). Altered regulation of hepatic

heme biosynthesis and urinary porphyrin excretion during prolonged

exposure to sodium arsenate. Toxicol. Appl. Pharmacol. 43, 361–371.

[iSI][Medline]

This article has been cited by other articles:

K. L. Nuttall

Interpreting Mercury in Blood and Urine of Individual Patients

Ann. Clin. Lab. Sci., July 1, 2004; 34(3): 235 - 250.

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> Hi,

>

> My child also had multiple specialists calling her different

things....her official diagnosis was high functioning PDD-NOS,

moderate verbal apraxia, sensory processing disorder, severe speech

delay, and hypotonia. She was very loving, had okay eye contact, and

did not have meltdowns. None-the-less, she had issues...including

excema and a very poor immune system.

>

> Long story short, after coming to this great list first and then

branching out into the autism spectrum ones, we were able to diagnose

her correctly. Beyond any reasonable doubt, unequivocally, no-

mistaking it....she had mercury poisoning. Hair tests, urine tests,

and stool tests all confirmed it. Chelating has reversed her

conditions almost 100%. She will enter kindergarten in two weeks

mainstreamed needing speech therapy once a week.

>

> I realize not everyone's child is like my daughter. I'm not saying

all children with issues have to be mercury poisoned. She also had

yeast issues and viral issues (making antibodies to the measles virus

like crazy). But at the end of the day, mercury was her biggest

problem. It's an avenue worth pursuing, even if it doesn't turn out

to be your child's. It can't hurt to rule it out.

>

> If one was to line up all of the symptoms of mercury poisoning with

all of the symptoms of the autism spectrum, including apraxia,

ADD/ADHD, and many other of the disorders that plague our children,

there are no differences. They aren't kind of similar...they are

identical. Anyone interested in more info may email me off line. I'm

happy to help.

>

>

>

[Guest guest]

So out of the two options mentioned, hair test or urine sample, which

method do you recommend that I try? Or should I try both? I am

interested in pursuing this, at the very least it will rule out the

possibility.

Also, is it worth asking his dev. pediatrician to help me with this

test? Has anyone else asked his/her doctor for it?

> > Hi,

> >

> > My child also had multiple specialists calling her different

> things....her official diagnosis was high functioning PDD-NOS,

> moderate verbal apraxia, sensory processing disorder, severe speech

> delay, and hypotonia. She was very loving, had okay eye contact,

and

> did not have meltdowns. None-the-less, she had issues...including

> excema and a very poor immune system.

> >

> > Long story short, after coming to this great list first and then

> branching out into the autism spectrum ones, we were able to

diagnose

> her correctly. Beyond any reasonable doubt, unequivocally, no-

> mistaking it....she had mercury poisoning. Hair tests, urine tests,

> and stool tests all confirmed it. Chelating has reversed her

> conditions almost 100%. She will enter kindergarten in two weeks

> mainstreamed needing speech therapy once a week.

> >

> > I realize not everyone's child is like my daughter. I'm not

saying

> all children with issues have to be mercury poisoned. She also had

> yeast issues and viral issues (making antibodies to the measles

virus

> like crazy). But at the end of the day, mercury was her biggest

> problem. It's an avenue worth pursuing, even if it doesn't turn out

> to be your child's. It can't hurt to rule it out.

> >

> > If one was to line up all of the symptoms of mercury poisoning

with

> all of the symptoms of the autism spectrum, including apraxia,

> ADD/ADHD, and many other of the disorders that plague our children,

> there are no differences. They aren't kind of similar...they are

> identical. Anyone interested in more info may email me off line.

I'm

> happy to help.

> >

> >

> >

>

[Guest guest]

So out of the two options mentioned, hair test or urine sample, which

method do you recommend that I try? Or should I try both? I am

interested in pursuing this, at the very least it will rule out the

possibility.

Also, is it worth asking his dev. pediatrician to help me with this

test? Has anyone else asked his/her doctor for it?

> > Hi,

> >

> > My child also had multiple specialists calling her different

> things....her official diagnosis was high functioning PDD-NOS,

> moderate verbal apraxia, sensory processing disorder, severe speech

> delay, and hypotonia. She was very loving, had okay eye contact,

and

> did not have meltdowns. None-the-less, she had issues...including

> excema and a very poor immune system.

> >

> > Long story short, after coming to this great list first and then

> branching out into the autism spectrum ones, we were able to

diagnose

> her correctly. Beyond any reasonable doubt, unequivocally, no-

> mistaking it....she had mercury poisoning. Hair tests, urine tests,

> and stool tests all confirmed it. Chelating has reversed her

> conditions almost 100%. She will enter kindergarten in two weeks

> mainstreamed needing speech therapy once a week.

> >

> > I realize not everyone's child is like my daughter. I'm not

saying

> all children with issues have to be mercury poisoned. She also had

> yeast issues and viral issues (making antibodies to the measles

virus

> like crazy). But at the end of the day, mercury was her biggest

> problem. It's an avenue worth pursuing, even if it doesn't turn out

> to be your child's. It can't hurt to rule it out.

> >

> > If one was to line up all of the symptoms of mercury poisoning

with

> all of the symptoms of the autism spectrum, including apraxia,

> ADD/ADHD, and many other of the disorders that plague our children,

> there are no differences. They aren't kind of similar...they are

> identical. Anyone interested in more info may email me off line.

I'm

> happy to help.

> >

> >

> >

>