A family with cardiomyopathy

A Family with Cardiomyopathy* I . KARIV, M .D ., F .A .C .C .P ., A . SZEINBERG, PH .D .,

B,

KREISLER, M .D .

and M .

I.

FABIAN, M .sc .,

L.

SHERF, M,D .,

ZELTZER, M .D .

Tel-Hashomer and Tel-Aviv, Israel HE CLINICAL features of cardiomyopathy include a history of dizziness or loss of consciousness, cardiac arrhythmias and the possi-

activity [15-17] . The composition of the assay mixture was identical with that used in the method of Colombo et a] . [14] but contained cystein in the final concen , tration of 1 DIM . The cystein stock solution (0 .24 M) was prepared daily by dissolving cystein hydrochloride in .05 0 M tris buffer, pH 9.0 and adjusted to pH 9 .0 with 1 .0 N potassium hydroxide . This assay was carded out at 25 ° c . All spectrophotometric assays were performed by means of a Beckman DU Spectrophotometer equipped with constant temperature thermospacers . Reagents were equilibrated to the assay temperature prior to the preparation of the assay mixtures . SCOT activity was expressed in Reitman-Frankel units per milliliter. The activity of other enzymes was expressed in international units per 1,000 nil . of serum, 1 I . U . representing the activity catalyzing the transformation of 1 µM of substrate per minute [18] . Isozymes of lactic dehydrogenase were examined by agar gel electrophoresis according to the method of Wieme et al . [79], using the staining procedure of Tsao [20], and evaluated by visual comparison of serums from the patients and normal subjects . Agar gel electrophoresis for separation of glutamic oxalacetic transaminase (GOT) isozymes was performed according to the method of Kar and Pearson [27] and the staining procedure of Decker and Rail [22] .

T

bility of sudden death . The electrocardiogram indicates atrioventricular conduction defects, intraventricular block with ectopic beats, and sometimes the pattern of Wolff-ParkinsonWhite . The heart is usually enlarged on the roentgenogram or has an "unusual" shape [1-81 . The familial characteristic depends upon finding a number of offspring affected in one family . Most of the described pedigrees of this condition conform to genetic transmission by an autosomal dominant gene with incomplete penetrance [9] . In the family described herein several members were affected . Two suffered from AdamsStokes attacks which necessitated the implantation of cardiac pacemakers . Serum enzyme abnormalities were also found which may contribute to the understanding of the nature of the disease . MATERIALS AND METHODS The family consisted of seventeen living descendents of three generations, all of whom were examined . Three additional members of the family died prior to this investigation ; two of these three died suddenly and probably were affected by this disease . (Fig . 1 .) Serum glutamic oxalacetic transaminase (SGOT) was determined by the method of Reitman and Frankel [10] ; aldolase (at 37°c .) by the method of Beisenherz et al . [71] using triethanolamine buffer, 0 .05 M, pH 7 .4, instead of collidine buffer ; lactic dehydrogenase (LDII) (at 25 °c .) according to the method of Wroblewski [12] ; alpha hydroxybuLyric dehydrogenase (HBD) (at 25 ° c .) according to the method of Elliott and Wilkinson [73] . Creatine phosphokinase (CPK) was determined (at 37 ° c .) by a modification of the method of Colombo et al . [14], based upon observations that the addition of cystein to the reaction mixture results in increased enzyme

CASE REPORTS CASE 1 .

The propositus, I . S . (ni-5), was first examined by us at the age of sixteen . He had developed well and performed physical work without difficulty . Two years previously pulmonary tuberculosis was suspected on routine examination, although not confirmed on yearly roentgenographic examinations. On the last examination it was found that the heart had grossly enlarged during the previous year and the patient was referred to us . The subject was a well developed boy without any signs of heart failure or other abnormalities, but a protodiastolic third heart sound could be heard and the blood pressure was 150/90 mm . Hg. All peripheral pulses were palpable . The electrocardiogram (Fig . 2A) showed normal sinus rhythm with negative P waves in leads in and aVF ; very large QRS com-

*From the Institute of Cardiology and the Department of Chemical Pathology, Government Hospital, TelHashomer, and The Medical School, Tel-Aviv University, Tel-Aviv, Israel . Manuscript received April 21, 1965 . 140

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Cardiomyopathy-Rariv et al .

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FIG . 1 .

plexes ; downward displacement of the S-T segment with negative asymmetrical T waves in the leads showing upright QRS complexes . Of note were the conspicuous Q waves in lead aVL and the presence of Q waves in leads V s and V6- The electrocardiogram was interpreted as diagnostic of left heart hypertrophy and strain . The roentgenogram (Fig . 3A) showed a grossly enlarged heart shadow with normal pulsation and with no pulmonary congestion . During a year of follow-up, there were no complaints or disturbances . The boy continued to perform

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Family tree . light work, but four months after the initial examination the electrocardiogram (Fig. 2B) showed disappearance of the Q waves with the development of a left bundle branch block pattern and the roentgcnogram (Fig . 3B) showed further enlargement of the heart shadow. CASE 2 . I) . R . (u-5), uncle of the propositus, was well until the age of twemy-six when he fainted for the first time, while bicycle riding . Since then he experienced repeated bouts of dizziness and loss of conscious-

2

Fm . 2 . Case I (m-5), electrocardiogram. A, at first visit . (Precordial leads V1, V4 and V6 are half standard .) B, four months later . voL . 40,

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Cardiomyopathy-Kariv

et al .

3A

3B

Fic. 3 . Case 1 (nn-5), chest roentgenogram . A, control film one year before first visit . B, four months after first visit . nesss . These were never accompanied by convulsions or urinary incontinence . At the age of twenty-eight, when the attacks became more frequent, he was admitted to another hospital . During two years of hospitalization the attacks recurred, sometimes several times a day and sometimes at intervals of a few days . Of a variety of drugs, including ephedrine and large doses of prednisone, only Isuprel ® , in increasingly large amounts (from 60 to 430 mg . per day), had any effect. Physical examination revealed no abnormalities except for disturbances in rhythm . The electrocardiogram (Fig . 4) from the early period showed changing atrioventricular block from 2 : 1 and 3 :1 to complete block with ventricular rate 25 to 32 and a widened QRS complex (0 .16), left axis deviation with tall R waves in leads I and aVL (R waves in lead aVL = 30 mm .) and a right bundle branch block pattern . In other recordings a typical Wolff-Parkinson-White pattern was seen . (Fig . 4 .) The roentgenograin showed enlargement of the heart with normal lungs . On laboratory tests, which included a blood count, urinalysis and examination of the feces for parasites, blood levels of urea, electrolytes including calcium and phosphorus, fibrinogen, proteins and protein electrophoresis were normal . The results of liver and kidney function tests were normal . The Kahn test yielded negative results. The results of a Congo red test and rectal biopsy for amyloidosis were negative . Intravenous pyelography, cholecystography and x-ray films of the digestive tract revealed no abnormalities . SCOT levels were consistently elevated, ranging between 76 to 269 Reitman-Frankel units, most of the values being closer to the upper level . The cause of the increased transaminase remained unexplained . In 1960 the patient was sent to the United States for implantation of a cardiac pacemaker . For a year there were no further attacks of arrhythmia or AdamsStokes seizures and he returned to work . After a year the electrode broke and repeat surgery was necessary . A third operation was performed two years later for the same reason.

When the patient was first examined by us in 1964 his general condition was good, the blood pressure was 140/80 mm. Hg, and there were no abnormalities except for the enlarged heart on the roentgenogram . CASE 3 . R. L . (a-2), sister of the preceding patient (Case 2) and aunt of the propositus, was forty-six years old and the mother of two children . She complained since the age of thirty-five of palpitations and occasional attacks of vertigo, accompanied by a premonition of falling . She was cold that her heart was healthy after repeated examinations revealed no abnormalities . When the patient was first examined by us in June 1964 there were no abnormalities except for a mild irregularity of the pulse . The blood pressure was 130/80 mm. fig. A roentgenogram of the chest did not show any abnormalities. The electrocardiogram (Fig. 5) showed multiple supraventricular premature beats, left heart hypertrophy in a vertical heart, and a right bundle branch block pattern . A few weeks later the patient suddenly lost consciousness for a few seconds . These attacks recurred several times during that afternoon . The electrocardiogram recorded at home showed a variety of cardiac irregularities including premature supraventricular beats, bouts of multiple extrasystoles, atrial fibrillation and cardiac standstill (with and without atrial activity) . (Fig . 5 .) Loss of consciousness was concomitant with cardiac standstill . Attacks recurred during transfer to hospital, the heartbeat being renewed following external cardiac massage . 'the attacks also recurred throughout the night at the hospital, despite external cardiac massage and use of an external cardiac defibrillator . Isuprel, injected intravenously, caused ventricular tachycardia ; smaller doses, which did not cause tachycardia, had no effect at all . In the morning the attacks remitted spontaneously and the electrocardiogram returned to the original pattern, with supraventricular premature beats . Prednisone therapy was started at an initially high dosage, which was gradually decreased and then stopped as the patient's condition remained stable . Two days later she AMERICAN JOURNAL OF MEDICINE

Cardiomyopathy-fiatir el al,

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Frr: . 4 . Case 2 (u-5), electrocardiogram . Lo(L tVollf-Parkinson-White configuration . Right. complcre a trioveutricular block with right bundle branch block pattern . complained of vertigo and weakness. The electrocardiogram showed a 2 :1 atrioventricular block . Treatment with prednisone was resumed and the patient was discharged from the hospital, medication to be continued at home. Two months later the patient was readmitted to the hospital with Adams-Stokes attacks . An electrode catheter was placed in the right ventricle and later an

internal cardiac pacemaker was implanted . Convalescence was slow because of fear and palpitations caused by interference . At present, several months after the implantation of the pacemaker, the patient feels fairly well, does light housework, but has not regained self-assurance . All seventeen living members of this family, representing three generations, were examined .

Fm . 5. Case 3 (u-2), electrocardiogram . Left, different forms of arrhythmia : B, C and D are from a continuous tracing ; the end of C and Dare during cardiac massage . Right, left heart hypertrophy in a vertical heart, incomplete right bundle branch block pattern, supraventricular premature beats . voc. . 40,JAnuear 1966



Cardiomyopathy-Kariv et al,

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FIG . 6 . Case 4 (o-1), electrocardiogram (lead VI) . Atrial tachycardia with changing block, incomplete right bundle branch block pattern. CASE 4 . P . R . (i-1), grandmother of the propositus, sixty-one years of age, stated she felt well . On examination, an increased blood pressure of 195 .1113 mm . Hg was the only abnormality . A roentgenogram revealed left ventricular enlargement and dilatation of the aorta, which could have been due to the hypertension and aging . The electrocardiogram (Fig. 6) indicated atrial tachycardia with changing block and incomplete right bundle branch block . Of the second generation, H . S . (mother of the propositus), thirty-eight years of age, and I . Y ., thirty-one years of age, sisters of the patients described in Cases 2 and 3, had no cardiac abnormalities . Three members of the second generation had died, one of rheumatic heart disease which was verified at necropsy ; the others had died suddenly at the ages of eight and thirty-five years, after repeated bouts of syncope, most probably Adams-Stokes attacks . Of the third generation, which consisted of twelve persons between the ages of five and nineteen, two TABLE I SERUM ENZYME ACTIVITIES IN NORMAL ADULT SUBJECTS*

Serum Enzymes

No. Persons Examined

Range of Activity

Mean Vainest

members in addition to the propositus were found to be affected . CASE 5 . M. L . (m-3), eighteen years old, son of the patient described in Case 3, had been excused from athletic activities since the age of thirteen because he tired easily . He complained of shortness of breath and palpitations on exertion or climbing stairs . Physical examination was within normal limits . The electrocardiogram showed a P-R interval of 0 .24 (atrial rate of 65) . The roentgenogram showed "rugby" shaped enlargement of the heart . CASE 6 . S . R . (m-8) was a twelve year old girt whose examination revealed only obesity . The electrocardiogram showed sinus rhythm, left axis deviation, QR pattern in leads I and a\% L (R wave in lead aVL = 11 mm.), high QRS voltage and flat T waves in the left precordial leads, The electrocardiogram was interpreted as compatible with left heart hypertrophy . The roentgenogram showed an enlarged heart. Her father had died suddenly two years previously, most probably in an,Adams-Stokes attack . The remaining nine members of the third generation had no complaints and the physical and roentgenographic examinations were within normal limits . In two members (m-7 and m-11), the electrocardiogram showed deep Q waves and in a third (m-0) occasional supraventricular premature beats . These changes are not considered sufficient to establish a definite diagnosis of cardiopathy . RESULTS

SCOT Aldolase LDH HBD CPK without cystein CPK with cystein .

40 25 40 40 27 19

10-40 2 .3-6 .4 83-185 55-150

19 f 9 .5 4 .2 -E 1 .12 127 +28 101 -E 30

-0 .2-1 .2 0 .36 f 0 .4 0 .4-5 .5 2 .4 f 1 .5

* The activity of SGOT is expressed in ReitmanFrankel units per milliliter of serum. The other enzyme activities are expressed in international units per liter of Serum . t t standard deviation .

A definite clinical pathologic condition compatible with cardiomyopathy was found in six of the living seventeen descendents of this family examined (the grandmother of the propositus, two members of the second generation and three of the third generation) . Three additional members of the third generation had doubtful pathologic changes indicated by the electrocardiogram . Three members of the second generation died suddenly, two of them probably from Adams-Stokes attacks due to cardiomyopathy . AMERICAN JOURNAL OF MEDICINE



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Cardiomyopathy-Karia et al, Serum Enzyme .4ctwities . The normal values for serum enzyme activity obtained in our laboratory on examination of healthy adult subjects are presented in Table I . The results obtained for the affected family are presented in Table a and summarized in Figure 1 . Elevated levels of enzymatic activity were observed in several family members . Among the six persons in whom the diagnosis of cardiomyopathy was established on the basis of clinical, roentgenographic and electrocardiographic examinations, increased activity of all the enzymes examined was found in the following three male subjects : the propositus (nl-5), without any clinical symptoms, but with marked cardiomegaly and definite electrocardiographic changes ; his cousin (m-3), with cardiomegaly, slight electrocardiographic changes and complaints of excessive fatiguability ; and his uncle (n-5), with the most pronounced clinical symptoms (Adams-Stokes attacks), who required implantation of a pacemaker . On the other hand, the severely ill aunt (n-2) with typical Adams-Stokes symptoms (who also had had a pacemaker implanted) showed only occasional slightly increased activity of serum lactic dehydrogenase and aldolase . The female cousin (m-8) with cardiomegaly and electrocardiographic changes but without any clinical symptoms had, on one occasion, increased LDH and HBD activity, whereas the other enzymes were

normal . On another occasion only a very slight increase in LDH activity was observed . The grandmother (1-1) with an abnormal electrocardiographic pattern did not show any serum enzyme abnormality . Among the family members considered healthy on the basis of clinical, roentgenographic and cardiac examinations, serum enzyme activity above the range established as normal in adults was observed in four children . In two members (TTf-7 and nt-10) LDH and HBD activity was increased, in one (nI-12) LDH and aldolase activity was increased, and in one (nt-11) only aldolase activity was slightly increased on one occasion . Since a greater activity of serum aldolase has been reported in normal children than in adults [23-25], we examined the activity of this enzyme in a control group of twelve healthy children three to fifteen years of age . In none of them, however, did we find increased values as were observed in some of the children in the family described here (activity, 7 .4 to 11 Units) . The serums of two members (n-5 and uT-5) (total LDH activity 360 and 720 I .U . per L) exhibited a significant increase in LDH 1 and LDH 2 fractions . A similar pattern was observed in several patients with acute myocardial infarction, whereas patients with infectious hepatitis showed a significant increase in the LDH 4 and LDH 5 fractions .

TABLE 11 SERUM ENZYME ACTIVITIES IN THE AFFECTED FAMILY* I

I

Case No ., Sex and Age .) (yr

Clinical Diagnosis

T.DII

HBD

1-1, F, 61 tt-2, F, 46 u-3, F, 38 u-5, xf, 32 u-6, F, 32 ru-1, M, 13 su-2, F, 16 m-3, M, 18 ,uA, F, 19 ut-5, M, 16 no-6, F, 1B u-7, F, .5 uF8, F, 12 Bt-9, F, 14 iii-10, M, 5 nn-11, F, 6 ut-12, M, 13

Affected Affected Normal Affected Normal Normal Normal Affected Normal Affected Normal Normal Affected Normal Normal Normal Normal

181, l63 168,254,269 153, 105 360 260 111, 106 147 125 326 182, 178 720,634,537 130 08 792, 264 182 296, 202 182, 173 226, 146

128, 134 137, 91 94, 72 276 221 80, 74 98 54 26'0 134, 138 470,390, 371 81 26,4 138, 207 130 178, 134 106, 127 146, 108

CFK without Cystcin 0 0.5 0.4

2 .9 0, 0 .2 3 .4,5 .6 0 .8

CPK with Cystcin

7'

5.9 0 .8,2 .0 73.8

0 2 .1, 1 .3 1 .1, 2 .1

Aldnlase

SCOT 13, 38 38, 15 11 65 58 4, 24 6 14 122 30, 16 91, 177, 135 7 16 ; 30 16 38 12, 24 18, 16

5 .4 . 5 .4, 5 .0, 9 .9 9 .7 4 .1, 4 .6 4 .6 13.8 3 .2, 15.5, 3 .5 3 .8, 2 .7 4 .4 7 .4, 71.1,

6 .4 6 .7, 8.4, 3 .0, 6.4 5 .4 21 3 .3 17 .6 . 74.9 4 .7 58 7,0

*The results of examination of several blood samples obtained from the same subjects within a fmsr month period are included . Activities above the upper range obtained in normal adult control subjects are italicized . The activity of 5G0"F' is expressed in Reitman-Frankef units per milliliter of serum . The other enzyme activities are expressed in international units per liter of scrum . VOL . 40, JANUARY 1966

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Cardiomyopathy-Kariv et al .

According to several investigators, electrophoresis of tissue homogenates on agar gel reveals two GOT fractions : fraction 1 (anodic), which is derived from the soluble cell content, and fraction 2 (cathodic), representing the enzyme bound to mitochondria [26,27] . In our own control experiments these two fractions were demonstrated in homogenates of heart muscle, skeletal muscle, liver, spleen and lung obtained within a few hours after death from the tissues of several patients who had diseases other than cardiopathy . Extracts of washed mitochondria, prepared from muscle of a normal heart, revealed only fraction 2 . Examination of the serums of one of our patients with cardiomyopathy (nt-5) (total SGOT activity 111 units per ml .), five normal subjects and four patients with fresh myocardial infarction demonstrated the presence of fraction 1 only . COMMENTS

The seventeen living descendents of three generations in the family were all examined and six of them were found to be clinically affected . No signs of coronary heart disease, rheumatic or congenital heart disease or myocarditis were found except in the grandmother (i-1), aged sixty-one, who had hypertension, but with changes in the electrocardiogram not characteristic of arteriosclerotic heart disease . No neuromuscular disturbances were found and diseases such as amyloidosis and hemochromatosis were excluded . There were several prominent findings in this family : the arrhythmia which was sometimes very severe, the cardiac enlargement, the electrocardiographic changes and elevated levels of serum enzymes . The high incidence of arrhythmias has been stressed by previous investigators and in a recent summary [28] was reported as high as 33 per cent . Of our six cases, three presented with arrhythmias : two with Adams-Stokes attacks and one with atrial tachycardia . The incidence of arrhythmias is probably even greater than 33 per cent because in all the surveys of familial cardiomyopathy published, cases of sudden death are reported as due to tachycardia or ventricular fibrillation with Adams-Stokes attacks . Sometimes the AdamsStokes attack is the first sign of the disease, as in patient D . R . (n-5), and sometimes the patient has minor disturbances of the rhythm, such as premature ventricular or supraventricular beats, and the Adams-Stokes attack appears later, as

in patient R . L . (n-2) . In our family there were two members who died suddenly and one of them, I .R . (n-4), was known to have suffered from attacks of loss of consciousness and convulsions ; he died during such an attack . Unfortunately, no electrocardiogam was recorded . Enlargement of the heart is usually found and, in fact, in the first report the syndrome was named familial cardiomegaly on this account [1] . Cardiomegaly was found in five of our patients : in three it was indicated by the roentgenogram and the electrocardiogram, in one by the roentgenogram only, and in one by the electrocardiogram only . In the sixth patient, P . R . (i-1), sixty-one years of age, enlargement of the left side of the heart was found with widening of the aorta, but these findings were considered to be due to hypertension . The importance of the electrocardiogram in diagnosing cases of cardiomyopathy has been emphasized by many investigators . In a previous report [6] we stressed the importance, especially in children and adolescents, of the finding of deep Q waves in the leads on the left side of the chest and in leads I and aVL or III and aVF, and pointed out the peculiar evolutionary pattern of electrocardiographic changes : The deep Q waves, so common in younger patients, disappear in time with the appearance of intraventricular block, especially left bundle branch block . In our first case (the propositus) this specific electrocardiographic evolution occurred in the space of a few months . The syndrome of Wolff-Parkinson-White was found in some of the tracings obtained on D . R . (n-5) . Several other investigators have stressed the frequency of this syndrome in familial cardiomyopathy and its diagnostic importance . The present investigation demonstrates that familial cardiomyopathy should be placed in the category of muscle diseases in which increases in serum enzyme activity may be found . The myocardial origin of the enzymes in this condition is supported by the observation that the LDH isozyme pattern observed in the serums of two of our patients was similar to that found in myocardial infarction . The SGOT isozyme examination, revealing only the presence of the soluble sarcoplasmic GOT fraction in the serum of the cardiomyopathic patient, favors the view that the underlying mechanism leading to increased activity of the serum enzymes in this condition is due to a change in cell membrane permeability, rather than cellular destruction or a AMERICAN JOURNAL OF MEDICINE



Cardionlyopathy--Karth mitochondrial defect. The cause of the increased permeability is not known . It might result from a structural anomaly or an insufficient supply of energy necessary for the proper functioning' of the membrane because of anoxia or some metabolic lesion 311 . The marked differences in the pattern and degree of increase of the serum enzyme activity in affected members of the family herein described could not be correlated to the severity of the clinical manifestations of the disease . The most salient changes in serum enzyme levels were observed in the affected male subjects, whereas female subjects with similar clinical, roentgenographic or electrocardiographic findings showed a normal or nearly normal pattern . The increases were greatest in the asymptomatic male subject (ni-5), whereas a female subject requiring implantation of a pacemaker (u-2) demonstrated only inconsistent mild increases of LDH or aldolase activity . These observations suggest that enzyme release from the affected myocardium may be influenced by physiologic parameters differentiating the sexes . A hormonal influence on serum enzyme levels was demonstrated by the finding of increased serum creatine phosphokinase in hypothyroidism [ .32,33] and of hyperaldolasemia in animals after the administration of ACTH or cortisone [25] . The majority of genetic investigations of families with cardiomyopathy reported previously suggested transmission by a dominant autosomal gene with variable expressivity and incomplete penetrance [6,9] . The present family conforms to this pattern of heredity . Of special interest is the apparently normal female carrier, n-3, whose son, mm5, is among those affected . A similar case of nonpenetrance may be found in the family described by Barry and Hall (Case c-9) [9] . When we first observed elevated levels of serum enzymes in the affected family, we hoped that this parameter could help in the detection of asymptomatic or preclinical cases . However, in our subject (n-3) all enzyme activity was normal, so that in this respect also the abnormal gene lacked penetrance . The abnormal findings in four children (in-7, 111-10, n1-11, and 111-12) necessitate follow-up studies . It is possible that the occasional elevations noted in these cases may be of no significance, for although no hemolysis was visible in their blood samples (thus avoiding one source of error in serum enzyme determinations), the effect of exercise was not investigated and the control sample of norVOL . 40,

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mal children was small . However, the possibility cannot he excluded at present that these findings represent an early expression of the abnormality and additional studies are required . A note of caution should be expressed about generalizing on the results observed in this family or applying them to other families with cardiomyopathy . This was demonstrated to us during the preparation of this report, when we had an opportunity to study serum enzyme activity in a second family described previously by Kariv et al . [6] . In five affected members, two male subjects (Cases 2 and 8) and three female subjects (Cases 4, 6 and 7), the serum activity of SGOT, LDH, HBD, CPK and aldolase was normal . The broad and variable pattern of clinical and pathologic manifestations, such as the severity of the disease and its rate of progression, changes in the electrocardiographic pattern, the extent of cardiomegaly, the deposition of nonmetachromatic neutral polysaccharides or of glycogen in the cardiac muscle [9,34], suggest the possibility that several entities have been provisionally grouped together because of lack of differential diagnostic criteria . Barry and Hall proposed, mainly on pathologic grounds, the existence of three distinct groups of cardiomyopathy with familial incidence [9j . It is possible that the serum enzyme pattern may provide another parameter which will help in classification and differentiation of these conditions . SUMMARY

A family in which six members of three generations had cardiomyopathy is described . In two affected patients Adams-Stokes attacks developed and implantation of an artificial pacemaker was required . The mode of inheritance conformed to transmission by a dominant gene with variable expressivity and incomplete penetrance . Investigation of serum enzymes demonstrated significantly increased activity of lactic dehydrogenase, alpha hydroxybutyric dehydrogenase, aldolase, glutamie oxaloacetic transaminase and creatine phosphokinase in all the affected male subjects . In the affected female subjects, only slight deviations from normal enzyme activity were observed . Heterogeneity of the condition designated as familial cardiomyopathy is suggested by the observation that in a second family with this disorder normal serum enzyme activity was found in all subjects .

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