Magnesium metabolism in Huntington's chorea

Magnesium Metabolism in Huntington’s Chorea By JOHN

C. DESPER AND EDMUND B. FLINK

E. JONES, PAUL

Human magnesium deficiency states are known to be associated with tremor, choreiform and athetoid movements, delirium and convulsions. In order to assess a recent report of altered magnesium in Huntington’s metabolism chorea, 6 patients with the disease have been studied with complete balance studies, exchangeable magnesium studies, erythrocyte and ultrafiltrable magnesiums and 2 patients with spinal fluid magnesium determinations. Balance

S

referrable

YMPTOMS felderl

in a group

early report

without most Hanna

tremor,

has been

frequently

sorption,

choreiform

following losses

al.6 have

with

Since

hypomagnesemia

and athetoid

movements,

prolonged

of disorders. inadequate

gastric

the

by Hirsch-

glomerulonephritis.

and Flink,3j4

in a variety

through

reviewed

were first recognized

chronic

of Miller2

reported

seen

or excess et

to hypomagnesemia of patients

and the reports

associated

convulsions,

studies failed to suggest any abnormalities. Exchangeable magnesium28 values were within normal ranges (4.3 +- 0.7 mEq./Kg. at 24 hrs.), as were erythrocyte magnesium determinations (5.29 C 0.42 mEq./L.). Ultrafiltrable magnesiums were normal and the 2 spinal fluids evaluated had normal magnesium values. These results are not compatible with the hypothesis of altered magnesium metabolism in Huntington’s chorea.

suction

various

this

with or

delirium

and

Hypomagnesemia

is

dietary

intake,

or diarrhea.

malab-

Smith5

clinical

manifestations

finding

significant

and

of hypo-

magnesemia. In

1963,

erythrocyte of these

cations

our chance show status From

Kenyon

and

magnesium

in a group

observations

any evident

reported

of

Morgantown, West Virginia. These studies were carried 05578-AMP) and supported Received for publication EditoriaE Comment: The

abnormality,

in Huntington’s

Medicine, out

with Huntington’s

with this disease

magnesium

in

West our

elevations

in the face of normal

of 20 individuals

metabolism

Department

levels

on one patient

erythrocyte

of magnesium the

Hardy7

and calcium

Virginia

Clinical

seemed

of

(USPHS

can be made

While to

of the

worthwhile.

School

Unit

of

levels

failed

an assessment

University,

Research

chorea.

had earlier

chorea

by VSPHS Grant NB 03152. Jan. 22, 1965. diagnosis of Huntington’s chorea

serum

Medicine, Grant

with

AM

certainty

only when the family history is positive. The choreiform movements differ in no essential detail from chorea caused by other factors, the abnormal movements depending on the site of the lesion and not the pathologic process underlying it. The search for evidence of a metabolic defect in Huntington’s

chorea

has been

long

and relatively fruitless. Kenyon and Harvey (1963) estimated the serum and erythrocyte magnesium and calcium levels in a group of 20 patients with adult chorea. In 4 of those patients, the family history was negative, in 2 it was unknown, in the remaining 14 the family history was apparently typical of Huntington’s chorea. An elevation of erythrocyte magnesium levels was found in some patients with chorea, which on statistical evaluation was just short of the 5 per cent level of significance. The serum magnesium was normal. There was also a tendency for patients without famiIy history to show an over-all higher 813 METABOLISM,

VOL.

14, No. 7 (JULY ), 1965

814

JONES,

DESPER AND FLINK

The results of complete balance studies, exchangeable magnesium determinations, serum and erythrocyte magnesium levels and ultrafiltrable magnesiums in 6 patients with Huntington’s chorea are presented. METHODS Patients:

Five

females

ranging

in age

from

34 to 60 and

on our Clinical Research Unit. All had family histories more generations. All had classical associated neurologic had least ambulatory as part

impairment and had of their

spinal fluid. ~&oratory mission.

of the group normal clinical

neurologic

Methods:

Constant

as would laboratory

evaluations All patients

diets

were

and had

started

male

age

magnesium

been

eating

determinations adequate

of 3 days

determinations. studied. Stools

ad prior

30 were

known for The male

he expected from his age. results. Two of the 6 had

a minimum

balance data or exchangeable magnesium over 8 to 14 days in 5 of the 6 patients

one

of involvement manifestations.

lib

two or patient

All patients were lumbar punctures we’re

to

studied

diets any

done

on thr

prior

to ad-

collections

Balance observations were collected in new

were gallon

for made paint

cans and homogenized by the method of Newell.8 Aliquots of the balance diets were homogenized and individually analyzed. Standard Kjeldahl digestion technics were employed in the processing of both diets and stool. Standard flame photometric determinations of sodium and potassium were done. Magnesium and calcium determinations were done on a Zeiss flame photometer by the method packed

of Mac1ntyre.a Erythrocyte cells by a modification of

a modification

of

the

method

of

magnesium the above Fiske

and

determinations were done on washed, technic. Phosphorus was determined by Subbarow,r” and nitrogen determined by

the method of Ferrari.11 Urine creatinines were done on a Technicon Autoanalyzer. Ultrafiltrable magnesium determinations were made by the method of Prasad and Flink.12 Magnesiumax

was

obtained

preparation, the isotope stool obtained. Gamma

from

was given counting

Brookhaven intravenously was done

National

Lahoratories.

and timed samples in a well scintillation

After of plasma, counter

appropriate urine, and employing

shows the results in 15 cases. In erythrocyte magnesimlr content. Table 2 of their paper 4 instances, the magnesium was markedly increased in the red cells (11.4, 19.1, 20.8 and 25.0 mEq./L.). Two of these patients had a negative family history, and one the family the family history is said to have been history was unknown, and in a further patient, positive. The only other patient without family history had a magnesium erythrocyte level of 2.5 mEq. which is the lowest result in the table. These results suggest that in these patients the magnesiunr metabolism may he abnormal and play a role in the etiology of their chorea. Jones et al. (1964) in a careful stucly of magnesium metabolism in 6 patients with chorea and a positive family history, found no evidence nesium metabolism. The conclusion that their results are not esis that Huntington’s chorea is caused by. or accompanied nesium

of any abnormality of magcompatible with the hypothby, a disturbance of mag-

metabolism, is the only possible interpretation of their work. mrrst he clearly recognized other than the hereditary type “adult chorea” Chronic and Harvey that patients diag(Bell, 1934). It appears likely, as suggested by Kenyon nosed as Huntington’s chorea are not a biochemically homogeneous group, and further studies of magnesium metabolism with particular emphasis on those patients without positive family histories may be rewarding. vol. 4. Cambridge University Huntington’s chorea. In Treasury of Human Inheritance. Press, 1934, p. 67. Kenyon, F. E., and Hardy, S. M.: A biochemical study of Huntington’s chorea. J. Neurol., Neurosurg. & Psychiat. 26123, 1963. E. B. Magnesimn metabolism in Huntington’s Jones, J. E., Desper, P. C., and Flink, Chorea.

Metabolism

14:000,

1965.

MAGNESIUM

METABOLISM

IN HUNTINGTON’S

815

CHOREA

mEq* 0 IO

0

20

0

20

Fig. L-Magnesium balances in 5 patients VaIues below the zero line represent positive balance, The scale is identical throughout.

chorea. with Huntington’s those above negative balance.

thallium activated sodium iodide crystal detector. Calculations magesiums (Mg2,8) were done with the following formulas:

a

Mgas Total =

PC. Mgas injected

E

specific activity Mg:

mEq./Kg.

=

for exchangeable

- ~c. Mg2s excreted to 24 hours (@mEq. ) of spot 24 hour urine Mgzs Total E

Weight

in Kg.

816

JONES,DESPERANDFLINK

Sodium

Potassium

Calcium

Nitrogen

Fig. 2 .-Balance data in patient P. S. are typical for the group. the zero line represent positive balance, those above negative balance.

Values below

RESULTS

The

results

of the magnesium and Wells’”

balances

Albright

from normal

was noted in any of the 5 patients.

in only one of the 5 during in sodium Typical

balance

balance

were noted

short-term

during

data for sodium,

are shown for patient Multiple

these

in figure

are presented by the methods of 1. As can be seen, no deviation

Reifenstein,

Calcium

balances,

balance and minor

the first few days balance

potassium,

calcium,

phosphorus

was attained fluctuations in 3 of the 5. and nitrogen

P. S. in figure 2.

determinations

were made of serum,

erythrocyte,

and ultrafiltrable

MAGNESIUM

METABOLISM

IN HUNTINGTON’S

817

CHOREA

TabIe 1 Patient and Age

Range of Range of Ultrafiltrahle Serum Magnesiums Magneaiums mEq./L.* mEq./L.*

Range of Elythrocyte Msgnesiums mEi&/L.*

Exchangeable bi;iq;; at 24 hours

Spinal Fluid Magnesium mEq./L.

4.3 *

2.4 + 0.14

Normal 1.86 z!I 0.14

values

1.18 r+ 0.1

5.29 -+ 0.42

0.7

N. W., 34 H. E., 51 D. M., 37 P. s. 60

1.8-2.0 1.6-2.05 1.9-2.0 1.8-2.0

1.15-1.3 -

5.2-5.5 4.9-5.3 4.8-5.7 4.9-5.0

4.4 3.6 4.6 3.8

2.56 -

M. L., 43

1.7-1.85

1.17-1.3

4.8-5.7

5.4

-

1.7-2.0

1.19-1.3

4.8-5.1

3.8

2.35

D. S., 30 (male) ‘Ranges

represent

magnesiums magnesiums (table 1).

a minimum of 6 determinations

per category.

in each patient and were entirely normal (table 1). Spinal fluid in the 2 patients who had lumbar punctures were normal

DISCUSSION

Our balance studies were designed primarily to test magnesium handling and were terminated in each case after normal magnesium balance was evident. The failure to develop calcium balance during short-term studies such as these is expected. Further, varying degrees of neurologic impairment and dementia made a standard level of activity impossible. Aside from minor fluctuations in sodium balances during the first few days in 3 of the 5 patients, the remaining balance data were entirely within normal limits. Exchangeable magnesiums in these patients fell within our normal ranges with the exception of minimal, unimpressive elevation in patient M. L. (table 1). MacIntyre et a1.,14 quoting the unpublished observations of Caesar and coworkers, and Petersen,l” found normal 24 hour values for exchangeable magnesium in the range of 4.5 mEq./Kg. This is also the same general order of values pubhshed by Silver et al. lo The availability of high specific activity Mgzs affords a means of attempting to assess body magnesium pools, but its short half-life (21.3 hours) virtually insures the inability to determine total body magnesium levels. Certainly, equilibrium between bone, soft tissue, and extracellular space has not occurred at 24 hours. Our limited observations in other patients do not suggest the attainment of equilibrium by 48 hours. Nonetheless, it appears meaningful that patients with Huntington’s chorea have values within normal ranges at 24 hours. As can be seen in table 1, we were unable to find any evident abnormalities in erythrocyte, serum or uhrafiltrable magnesiums. While the patients of Kenyon and Hardy7 tended to have been both older and to have had the disease longer, 2 of our patients were over age 50 and had values within the same ranges as our younger patients. It does not appear likely that the age of patients or duration of symptoms explain the differences in results.

818

JONES, DESPER AND FLINK

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Clinical

manifesta-

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John E. Jones, M.D., Assistant Professor of Medicine, Dept. of Medicine, West Virginia University, School of Medicine, Morgantown, W. Va. Paul C. Desyer, M.D., Trainee of the USPHS (5Tl-AM-538143). Edmund B. Flink, M.D., Professor ,of Medicine, Medicine, West Virginia University, School of Morgantown, W. Va.

magde174:

Dept. of Medicine,

J.

Clin.