Developments in the study of spindle leg syndrome

Hugo Claessen
Belgian Herpetological Society
Antwerp
August 1999
Last update: 17 August, 2002

Spindle leg syndrome, a condition that was identified as a problem many years ago, affects the front legs of metamorphosing tadpoles. The result is froglets which have weak, deformed limbs and which are seldom able to feed effectively and thus die. Last year I attended the 'Anuren Taggung 1998' in Germany which I have investigated and now produce my conclusions.

A German vet, Dr Thomas Wohrmann, from the University of Aachen, has examined, by histology, hundreds of affected Dendrobatids and has found the following:

1) The thyroid gland is always normal.
2) The forelegs always have muscular atrophy.
3) The spinal column has sub-total dystrophy.
4) The medulla oblongata is not closed.

Because I am an amateur, but wanting to fully understand what this meant, I spoke with veterinary professors in Belgium and the Netherlands and these are my conclusions:

1. Whilst the thyroid is histologically normal this does not confirm normal secretion of hormones which requires further investigation.

2. The muscular atrophy is the histological examination of the visible effect of spindle leg. The 'elbows' are fixed and the musculature has too few fibres, which are also small. (Gouda and Hak, University of Utrecht, 1995.)

3. The spinal column has sub-total dystrophy; it is not completely closed.

4. The medulla oblongata is not closed at all. This is the section of the brain that connects with the spinal chord.

The Biology
(Development stages are the standard stages of early development of anurans according to Gosner, 1960). In the development of frogs' eggs the closing of the Spinal column starts at stage 13, when the neural plate is formed. This closing is complete at stage 15 when a neural tube is completely formed. The Medulla oblongata stays open which is normal for amphibians. The closing of the Spinal column and the formation of the forelegs are controlled by a gene, the Homoobox-Gene XLHBox

If there is a disturbance of this gene, the frogs develop spindly legs. The German investigators were able to generate this in the laboratory and each time they introduced a disrupter the frogs developed Spindly Legs. The external influences on that gene are not known, but it is possible that the disrupter is introduced by the parents, by high temperature or radiation (perhaps UV?), after the eggs have been laid, but prior to the tadpoles becoming free swimming at Stage 25. 

If this is true, it means that it is too late to change the process once tadpoles have formed as the genetic information to produce Spindly Legs is set in the egg. Only the influences of temperature or radiation can generate a further disruption of the gene making it impossible to repair a disruption that has existed from stages 13 to 15. Therefore, in my opinion, if we wish to find the reasons for spindly leg, and its cure, we must look at the parents, not the tadpoles.

The human condition, Spina bifida, in which babies are born with a spinal column not completely closed, is also caused by the XLHBox 1 gene. The incidence of the condition has been demonstrated to be reduced by giving the mother large quantities of Folic Acid, and often Vitamin E, as a prophylactic. Both Spindly Legs and Spina bifida are conditions generated by a disruption of the same gene making it feasible that the same prophylactic could work, a possibility which must be worth trying with frog parents.

The Question
It is questionable how the frogs obtain these substances in the wild but it should be possible to give the frogs fruit flies dusted with Folic Acid and vitamin E powders but how, and in what quantities, as there is no information on dosage for amphibians? Pregnant women are frequently given a medication called OMNIBIOTA Prenatal which gives a dose of Folic Acid of 5mg and 12mg of Vitamin E for a woman of 55Kg body weight. This equates to O.lmg and 0.22mg/Kg respectively.

Folic Acid
Because Folic acid is one of the vitamins from the B complex, there is little risk of hypervitaminosis (overdosing). Information for fish and poultry gives a dosage of about 10 to 20 mg Folic acid /kg food. Daily doses of 20 mg/kg body weight would seem to be sufficient for fish and poultry but this is over 100 times the level indicated for humans.

Vitamin E
In a professional fish food for Tilapia and Trout, a dosage of 50-100mg/kg body weight of fish is given. This is again, at least, 200 times the level indicated for humans. Vitamin E prevents the formation of free radicals that can initiate the disruption of the relevant gene.

As our normally used vitamin and mineral supplements contain very low levels of both Folic Acid and Vitamin E, I suggest that some form of supplementation may be necessary, though a considerable amount of work will be needed to ascertain dosages. It may be that, in the first instance, a simple addition to the usual vitamin/mineral supplements might be tried.

The next text is from Brander G. C. & Pugh D. M 1977 Veterinary Applied Pharmacology and Therapeutics:

Folic acid, folinic acid, vitamin C and cyanocobalamin are connected with nucleic acid synthesis. The acid is also involved in ansmethylating actions along with cyanocobalamin, both in nucleoprotein formation and in fat metabolism through methylation in the synthesis of choline and methionine. Through this latter action folic acid and cyanocobalamin reduce nutritional requirements of choline and methionine. Clinically the symptoms shown in experimentally induced deficiencies are unlikely to occur. These symptoms include macrocytic anaemias with reduction in the numbers of all cellular elements of the blood, diarrhoea, skin, lesions, reduced growth rates in experimental animals and birds. It should be noted, however, that, as with para-aminobenzoic acid, which is a precursor of folic acid, small quantities of the gut 'active' sulphonamides would promote a deficiency, probably by reducing bacterial numbers and therefore the synthesis of this and other vitamins.

Therapy when an outbreak of (Vitamin E) deficiency disease is suspected usually consists of immediate administration of vitamin E and/or selenium in whatever form is appropriate and convenient. Nutritional requirements are not defined. This is possibly because the availability of the vitamin is conditioned by the composition of the diet. Where the level of unsaturated fatty acids in the diet is high, the vitamin requirements will also be high, but it should be remembered that other compounds and conditions besides these acids will depress absorption of vitamin E, including triorthocresylphosphate (in some species), possibly sulphaguanidine and gastro-enteritis. It must also be borne in mind that variations in mineral and carbohydrate concentrations in a diet will modify the symptoms resulting from a vitamin E deficiency or insufficiency. Deficiencies other vitamins such as choline may predispose muscles to the effects of vitamin E deficiencies.

Conclusions
Many people are trying to solve the problems of spindly leg and, whilst not suggesting that my ideas are the answer, I feel that they are worthy of further investigations. If you have any further information, ideas or criticisms please let us discuss them together. 

I can be contacted by e-mail on phyllos@online.be

Editor's note
Whilst some of Hugo's article above is conjecture, it is well thought out and would form an excellent basis for further research. If there are any members currently producing froglets with spindle leg it would be worth adding vitamin E and Folic Acid to the usual vitamin and mineral supplements to see if this alleviates the problem. Please let the rest of us know your results.

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