Friedreich' 5 Ataxia in Chi Idhood
Case Report with Possible Myocardial Infarction,
Cerebrovascular Thromboembolization, and
Persistent Elevation of Cardiac Specific LDH
Ehud Krongrad, M.D.,· and Howard A. Iooe. M.D.··

A seven-year old Caucasian girl with Friedreich's ataxia, cerebral thromboembolism, possible repeated myocardial infarctions and severe cardiac involvement is presented. The father and a paternal uncle both died of myocardial
infarction at an early age. Persistent elevation of LDH isoenzyme 5 following
angina-like attacks is reported for the first time in Frledreich's ataxia and suggests continuing damage to the myocardium.

T he clinical picture of Friedreich's ataxia (Fr at)

CASE REPORT

is well known.>" Onset of ataxia, hypoactive
or absent knee and ankle reflexes and progressive
cerebellar dysfunction are commonly the presenting
symptoms. Intermediate forms and families in
which one member presents the typical features
while others show only abortive forms are also
known.v"
Only a few reports have documented the onset of
the disease during childhood, particularly that with
severe cardiac involvement as a major manifestation.P-? The cardiac involvement in childhood
usually consists of electrocardiographic ( ECG )
changes," occasionally cardiomegaly.V'? anginal
pain or myocardial infarction.I-" and rarely congestive heart failure.v" Weare not aware, however, of
a documented clinical case supported by laboratory
evidence of myocardial infarction in the pediatric
age group. We found only one case report in which
serum glutamic oxalacetic transaminase (SGOT)
and serum glutamic-pyruvic transaminase (SGPT)
were elevated in a patient with Friedreich's ataxia."
This was the case in our patient on two different
occasions. In addition, persistent elevation of cardiac specific serum lactic dehydrogenase (SLDH)
was observed for more than 12 months and suggested for the first time laboratory evidence of continuous myocardial damage.

A seven-year-old Caucasian girl was admitted to Maimonides Medical Center for evaluation and treatment of congenital heart disease and chronic congestive cardiac failure.
The patient was the product of a normal full-term pregnancy
and delivery; subsequent growth and development were
normal. At the age of three years the patient was noted to
have a waddling gait and poor balance. Her gait resembled
that of a deceased sibling. Weakness was found in all
extremities without loss of muscle bulk. Deep tendon reflexes
were hypoactive and toe responses were flexor bilaterally.
Results of skull x-ray examinations, electroencephalogram
and serum creatinine were all reported as normal.
Because of a history of heart disease in a sibling, the
patient was referred for cardiac evaluation. A soft apical
systolic murmur was described, and the ECG was interpreted
as showing combined ventricular hypertrophy. Chest x-ray
films and cardiac fluoroscopy gave normal results.
At five years of age the patient was hospitalized elsewhere
because of abdominal pain and vomiting. Pertinent physical
findings included questionable distention of neck veins, liver
palpable 2 to 3 cm below the right costal margin, absent deep
tendon reflexes and flexor toe responses. The ECG showed
marked left ventricular hypertrophy. ST segments were depressed and deep Q waves were seen in leads II, III and
aVF. The chest x-ray picture showed marked cardiomegaly
and pulmonary congestion. The patient was digitalized and
received meralluride (Mercuhydrin). Pentaerythritol tetranitrate (Peritrate) was also given, and prednisone was added
because of the possibility of myocarditis. Episodes of rapid
heart rate occurred and complaints of abdominal and chest
pain associated with general pallor. At such times the ECG
showed tachycardia of 180 per minute. Diphenylhydantoin
(Dilantin) was given in an effort to reduce myocardial
irritability, and she improved enough to be discharged.
Three weeks later she was readmitted because of headache and vomiting. She was incoherent and the liver was
palpable 7 cm below the costal margin. The toe response was
questionably extensor on the right. Laboratory data, including spinal fluid examination, were noncontributory. After

• Associate, Division of Pediatric Cardiology, Department of
Pediatrics, Babies Hospital, Columbia University, College
of Physicians and Surgeons, New York.
··Professor of Pediatrics, State University of New York,
Downstate Medical Center; and Director of Pediatric Services Maimonides Medical Center, Brooklyn.

Reprint requests: Dr. loos, 4802 Tenth Avenue, Brooklyn
11219

644

FRIEDREICH'S ATAXIA IN CHILDHOOD
several days a left-sided flaccid paralysis developed which
was believed to have resulted from cerebrovascular embolization (CVE).
The patient's father died at 36 years of age following a
second myocardial infarction, the first of which occurred at
age 30. He had heen previously healthy. The diagnosis of
myocardial infarction was verified at autopsy which showed
marked coronary artery narrowing (Fig 1) and recent healing myocardial infarction as well as the scar of an old
myocardial infarct. The central nervous system was not
examined. The father's brother died at 39 years of age, also
following a myocardial infarction. He had been well until a
year before his death at which time diabetes mellitus was
diagnosed and managed by dietary treatment alone. Physical
and neurologic examination of his eight year old son gave
normal results as did the ECG and chest x-ray examination.
The father's sister was said to have had unsteadiness and a
tendency to fall, which she allegedly outgrew. She had two
children, now 7 and 12 years of age, whose physical and
neurologic examinations, ECG and chest x-ray films are
normal.
A sister of the patient first showed weakness and waddling
gait at 4Ji years of age at which time she was hospitalized
elsewhere. Ataxia, generalized weakness, and absent deep
tendon reflexes were found. The toe response was flexor
bilaterally. Mild lumbar scoliosis and spina bifida occulta at L5 and S-1 were found. The urinary creatine-creatinine ratio
was normal as was an electromyogram. A chest x-ray picture
disclosed cardiac enlargement which suggested congenital
heart disease. She died a few months later, three days after
having been readmitted for abdominal pain and vomiting. At
autopsy, marked idiopathic myocardial hypertrophy was
found, together with bronchopneumonia and passive visceral
congestion. No evidence of nervous or muscular disease was
found by routine studies. The coronary arteries and their ostia
were reported to be normal.
Physical examination of the patient at the time of admission at Maimonides Medical Center revealed an enlarged
heart. The palpable impulse was maximal in the sixth left
intercostal space in the anterior axillary line, and a left
precordial heave was noted. SI was normal, and S2 was
normally split. A high-pitched systolic murmur of grade 2/6
intensity was heard at the apex. Kyphoscoliosis and questionable bilateral pes cavus were noted. Neurologic examination"
revealed a child who could neither stand nor walk. A flaccid
left hemiparesis was accompanied by a decrease in muscle
bulk in the left arm and leg. Deep tendon reflexes were
absent in all extremities and plantar responses were extensor
on the left and flexor on the right. Left lower facial weakness
and slurred speech were noted. Nystagmus was absent.
Sensory responses to pinprick, touch, vibration and position
senses seemed intact, although testing for the latter was
difficult. She could sit alone without support but was unable
to stand erect on the right leg without assistance. She could
not maintain balance on the hemiparetic left leg. No involuntary movements were seen. Affect was appropriate for her
age. Intellect was estimated as dull normal.
Blood counts, urinalysis, serum electrolytes, spinal fluid,
electroencephalogram, chromosome analysis, and serum proteins as well as electrophoretic pattern were all normal. LE
cells were absent. Serum enzyme levels were SGOT 30 units
SGPT 60 units, SLDH 1,414 units, serum creatine phosph~
°Dr. S. B: B~own
c~rren~y
Assistant Professor of Neurology
and Pediatrics, University of Miami Miami Florida Formerly Chief, Pediatric Neurology,' Maimo'nides M~dical
Center.

CHEST, VOL. 61, NO.7, JUNE 1972

645

FIGURE I. Photomicrograph of coronary artery of the patient's
father (X 2.5). Severe, occlusive, intimal disease virtually
obstructs the lumen. The lesion is mainly fibrous with some
atheromatous material and smooth muscle cells.
kinase (CPK) 8 units, and aldolase 15 units. Total serum
cholesterol was 321 mg percent and total lipids 597 mg
percent. Serotonin and coproporphyrins were absent from the
urine. There was no aminoaciduria. The electromyogram
showed no myopathic or neuropathic potentials. Skull x-ray
films were normal. The ECG and chest x-ray pictures were
the same as previously described.
The suspicious family history, cardiomegaly, and the
neurologic observations led to consideration of the possibility
of Friedreich's ataxia. The autopsy findings of the deceased
sister were reviewed, and special stains of the central nervous
system specimens revealed marked demyelinization of the
posterior lateral columns and spinocerebellar tracts of the
spinal cord, loss of myocardial fibers with round cell infiltration and marked hypertrophy of the heart.
Attacks of "abdominal pain," vomiting, and sweating often
associated with tachycardia of 140 to 180 per minute occurred many times during the patient's hospitalization, with
pain often referred to the left arm. Carotid sinus pressure and
eyeball pressure failed to decrease the heart rate. Edrophonium chloride (Tensilon) test suggested sinus tachycardia.I?
Fever developed after one of these episodes at which time
the WBC was 13,700, corrected sedimentation rate 17 mm
per hour, serum amylase 102 units, SGOT 570 units, SGPT
370 units, and the SLDH 1,320 units, most of which was of
cardiac origin (isoenzyme 5) (Fig 2). The ECG showed
elevation of S-T segments in leads VI-Va consistent with an
"injury pattern" of the anteroseptal myocardial wall.
Anticoagulant therapy in the form of sodium warfarin
(Dicumarol) was initiated because of the possibility of
recent myocardial infarction, the history of CVE, and in view
of her currently limited physical activity and decreased
chance for self-injury.
An attempt to relieve the frequent episodes of tachycardia
with prolonged administration of neostigmine in addition to
digoxin, failed. Further, the elevated serum LDH persisted.
The persistence and reproducibility of this high level of
cardiac specific SLDH was verified on two different occasions
by splitting a sample of blood drawn and sending it to two
different laboratories. The results were similar and abnormally high.
Twelve months later she was readmitted because of a one
day history of severe back pain referred to both arms, and
persistent vomiting. ECG in the emergency room showed an
"injury pattern" of the anterior wall (Fig 3), and she was

KRONGRAD AND JOOS

646
FEVER

n

101" IOl"

1400
1300
1200
1100
1000
900
800
700
600
500

x--x--x--x---x--x--x--~~

~DH

400
300
200

.-,bt:-------=:::::::=:======~:::::::===-="""""""""""...-___tiIORIolAl

100 1r-

~

DAYS 4

5

6

7

---M~

GOT GPT

8910111213141516

NOVEMBER

FIGURE 2. Serum LDH, COT and CPT following severe attacks of abdominal pain and vomiting
as observed from November 5 to November 29. The LDH remained elevated for the following
glutamic-oxalacetic trans12 months, indicating possible continuing insult to the heart. COT
aminase, CPT
glutamic-pyruvic transaminase, LDH
lactic dehydrogenase, CPK
creatinephosphokinase. Initial levels of serum enzymes reported (10/5) were SCOT 44 p" SCPT 20 p"
SLDH 56 p,. The next day (10/6) SCOT 39 p., SCPT 24 p, and SLDH 500p,. First significant elevations were noted on October ninth.

=

admitted with a diagnosis of a possible myocardial infarction.
The prothrombin time was 36/12 seconds. The SCOT
reached 240 units on the second day of hospitalization at
which time the SCPT was 185 units and the CPK 30 units.
The SLDH which was 550 units at the time of admission rose
to 1160 units on the tenth day and remained abnormal
throughout her hospitalization. Repeated abdominal pain
occurred during her four weeks in the hospital until discharge. Neurologic findings were unchanged but bilateral pes
cavus was now definite.
COMMENT

The clinical findings of the patient and the
clinical as well as the autopsy findings on the
patient's sister are consistent with the diagnosis of
Friedreich's ataxia. Unfortunately, the upper central
nervous system, particularly the cerebellum, was
not available for pathologic review. Speculation is
possible, therefore, that the family reported herein
might have some other form of spinocerebellar degeneration. However, the diagnosis of a specific
variant even when the complete nervous system can
be examined is at times difficult, if not impossible.
Cerebellar degeneration in various degrees often
occurs in Friedreich's ataxia, and the final diagnosis
depends upon the extent of neurologic degeneration
in the various components of the central nervous
system. The same could be said of the clinical manifestations, as formes frustes, and transitional forms
do occur in many variations. At times even a prolonged follow-up may fail to define precisely the
exact variant.

=

=

=

Neurologic manifestations preceded cardiac involvement in both sisters. The absence of extensor
toe response as occurred in both sisters has been
previously noted by others. This was the case in
four of the patients reported by Boyer and coworkers.' In the patient reported by us, when the
extensor toe response appeared it was evidently
secondary to CVE.
Heart disease, however, is best known in Friedreich's ataxia. Hewer!' reported it to be present in
100 percent of adult patients. The same author was
unable to find any reference to descriptions of cardiac pathology in conditions such as Roussy-Levy
syndrome, familial spastic paraplegia and peroneal
muscular atrophy-conditions closely allied to Friedreich's ataxia. Clinical as well as ECG abnormalities, however, have been previously reported in
these diseases.P-"
The progressive cardiac damage in patients with
Friedreich's ataxia has been attributed to various
etiologic factors, including coronary artery disease
and small vessel occlusion.U-" The heart muscle
of the deceased sibling of our patient showed
marked and diffuse myocardial hypertrophy with
scattered areas of loss of myocardial fibers and
minimal round cell infiltration, consistent with findings reportedly associated with Friedreich's
ataxia.'! The absence of small vessel occlusion in
our autopsy material, could be accounted for by
the small block available for review and by the fact
that only about 10 percent of the arteries are

CHEST, VOL. 61, NO.7, JUNE 1972

FRIEDREICH'S ATAXIA IN CHILDHOOD
DATE

LI

t"ttJI.
B
",
11120

12I1~

12111

12/23

~

§

·I,. ·.II

12/1T

12/23

I"'::'
-:.:

;

I' ·

.,:'"

HI 20

',"

·I".'
"
II

:' .'

"

!!:

'1:1';

1

.nu

1"'.';'"
, . I c
•.;;..:

.

"

.

.

.

1 !l

C

,"

.'.,

I

;1j

.

f2l1~

':' j"'

.«

.

AVR

DATE

647

II

.:

"

iii: \'

,;

.~.

1"-

'"
.

I~'.

•

.:,.,.",
.

..,

't·,

, t · ~::-

.

~
-'-I- ':~

'

I

.

.

I.·'·'.····.··'·:
.·.'·'"·

•

+f-:~

.'.

>._" .': .:

~C·.~.

,

"""

'--

:, ,:

,,'

h,

.h

AVL

II
..

'."

AVF

ABC
D A B
C
FIGURE 3. ECG three weeks prior to admission (A), in the emergency room on the day of admission (B), two days (C), and eight days (D) thereafter.

narrowed. II
Only one other case of Friedreich's ataxia has
been reported in which the SGOT and SGPT were
elevated." Others have failed to find these enzymes
abnormal." The intermittent and episodic elevation of these enzymes as in our case may explain
such apparently diverse observations.'
In our patient, the severity of the "abdominal
pain" often extending to the left arm associated
with increased sweating, was very similar to that
seen in adults with severe anginal pains. The pain,
sweating, fever, and enzyme elevation are all compatible with a severe myocardial insult, most probably a myocardial infarction. The absence of more
specific ECG criteria such as the development of
deep q waves and persistent reduction in QRS
amplitude do not exclude this diagnosis, since ECG
changes depend on size of area involved. In addition, localizing ECG changes may not appear
following myocardial infarction if the tracing was
previously abnormal.
The differential diagnosis in atypical cases may
include such diverse possibilities as rheumatic fever,

CHEST, VOL. 61, NO.7, JUNE 1972

.

"

'!
. ifl

:..:.',:'
.. .....
0

chorea, cerebellar neoplasm, congenital heart disease and muscular dystrophy.v" Indeed, the deceased sister of our patient was once diagnosed as
having muscular dystrophy. Familial idiopathic
myocardiopathy had been suggested until the central nervous system was studied with special staining techniques. The patient herself had suffered a
CYE in the past, the neurologic consequences of
which confused and delayed the correct diagnosis.
CYE's are known to occur in association with
Friedreich's ataxia." This complication can occur
either as a result of detachment of a mural thrombus
secondary to a recent myocardial infarction or,
more commonly in the pediatric age group, as a
nonspecific complication in association with cardiac enlargement.
The father of our patient and his brother both
died of myocardial infarction in their thirties. Their
history of myocardial infarction at a young age is
very similar to that reported by Roth,15 Manning"
and Tyrer and Sutherland.P This could be consistent as an isolated "cardiac" form of Friedreich's
ataxia as has been suggested.12.15.16 However, in

KRONGRAD AND JOOS

648
none of the previously reported "isolated myocardial forms" was the extent of coronary occlusion or
its nature documented.
This report and the cases described by Nadas and
co-authors? with anginal pain or coronary occlusion l 4 in children and young adults suggest the possibility that a metabolic or toxic factor may cause Or
predispose to premature coronary occlusion in some
patients with Friedreich's ataxia.
In our patient, total serum cholesterol level, once
obtained, was elevated for age. No lipoprotein
pattern is available of the patient, her father, or
paternal uncle. It is therefore possible that the
"toxic" or "metabolic factor" previously referred to
in early reports;'? might be hyperlipoproteinemia.
This possibility has been neither documented nor
excluded in earlier cases or in our own.
The development of diabetes mellitus (DM) in
the paternal uncle one year prior to his death is
intriguing. Diabetes mellitus occurred in nine of 113
(8 percent) of patients with Friedreich's ataxia
studied by Hewer and Robinson" and in nine of 50
(18 percent) reported by Thoren.P These figures
are well above the figures obtained from population
surveys of the same age." In a survey of 286
siblings of 112 probands with Friedreich's ataxia,
130 had Friedreich's ataxia and 10 (7.7 percent)
had diabetes mellitus. Two of the siblings had
diabetes mellitus with no evidence of Friedreich's
ataxia. Podolsky and Sheremata'" who collected 74
patients in 14 families with diabetes mellitus and
Friedreich's ataxia, were unable to find this association in relatives other than sibs. The paternal
uncle reported by us is the first patient other than a
sibling to be reported with diabetes mellitus in a
family with Friedreich's ataxia. His sudden death
due to myocardial infarction is unlikely to be
related to diabetes mellitus in view of its mildness
and brief duration. Whether this association occurred by chance or is associated with the basic
anomaly remains speculative.
REFERENCES

1 Boyer SH IV, Chisholm AW, McKusick VA: Cardiac
aspects of Friedreich's ataxia. Circulation 25:493-505,
1962

2 Keith JD, Rowe RD, Vlad P: Heart Disease in Infancy
and Childhood. Ed. 2. New York, The Macmillan Company, 1967
3 Moore AAD, Lambert EC: Cardiomyopathy associated
with muscular and neuromuscular disease. In Paediatric
Cardiology (Watson H, ed). St. Louis, CV Mosby Company, 1968, p 766
4 Wilson SAK: Neurology (Bruce AN, ed). New York,
Hafner Publishing Company, Inc, 1970, vol 2, p 948963
5 Giannelli A, Serra A, Bacciagaluppi M: An atypical
hereditary spinocerebellar syndrome: a clinical and
genetic study. Acta Neurol Scand 41:387-412, 1965
6 Thilenius OG, Grossman GJ: Friedreich's ataxia with
heart disease in children. Pediatrics 27 :246-254, 1961
7 Nadas AS, Alimurung MM, Sieracki LA: Cardiac manifestations of Friedreich's ataxia. New Eng J Med 244:239
244, 1951
8 Graham GR: Frfedreich's disease. In Ciba Foundation
Symposium: Cardiomyopathies, London, 1964 (Wolstenholme GEW, O'Connor M, ed). Boston, Little, Brown and
Company, 1964, p 358
9 Gautier E, Richterich R: Valeur diagnostique d'activites
enzymatiques du serum en pediatrie. II. Constance et
specificite des anomalies enzymatiques. Helv Paediat
Acta 18:32-79, 1963
10 Moss AJ, Aledort LM: Use of edrophonium (Tensilon) in
the evaluation of supraventricular tachycardias. Amer J
Cardiol 17:58-62, 1966
11 Hewer RL: The heart in Friedreich's ataxia. Brit Heart J
31 :5-14, 1969
12 Thoren C: Cardiomyopathy in Friedreich's ataxia: with
studies of cardiovascular and respiratory function. Acta
Paediat Scand 53 Suppl 153:1-131, 1964
13 Tyrer JH, Sutherland JM: The primary spino-cerebellar
atrophies and their associated defects, with a study of the
foot deformity. Brain 84:289-300, 1961
14 James TN, Fisch C: Observations on the cardiovascular
involvement in Friedreich's ataxia. Amer Heart J 66:164175, 1963
15 Roth M: On a possible relationship between hereditary
ataxia and peroneal muscular atrophy; with a critical
review of the problems of "intermediate forms" in the
degenerative disorders of the central nervous system.
Brain 71:416-433, 1948
16 Manning GW: Cardiac manifestations in Friedreich's
ataxia. Amer Heart J 39:799-816, 1950
17 Russell DS: Myocarditis in Friedreich's ataxia. J Path
Bact 58:739-748,1946
18 Hewer RL, Robinson N: Diabetes mellitus in Friedreich's
ataxia. J Neurol Neurosurg Psychiat n.s, 31:226-231,
1968
19 Podolsky S, Sheremata WA: Insulin-dependent diabetes
mellitus and Friedreich's ataxia in siblings. Metabolism
19:555-561, 1970

Editorial Expression
The occurrence of cardiopathy in Friedreieh's
ataxia is well established, and could result from a
genetically determined biochemical abnormality affecting both the heart and the central nervous system. This excellent paper provokes speculation
concerning a possible relationship to the hyper-

lipidemias or diabetes, both familial disorders producing early diffuse coronary arterial disease, and
points to a need for continuing study in this context.
A. A. Douglas Moore
Norfolk
CHEST, VOL. 61, NO.7, JUNE 1972