Can Cystinosis Cause Coronary Artery Dilatation?

S. Olgar, K. Nisli, A. Dindar, R.E. Omeroglu, T. Ertugrul

Department of Pediatric Cardiology, Faculty of Medicine, Istanbul University, Istanbul 34200, Turkey

Abstract. In children, dilated coronary arteries areusually caused by Kawasaki�s disease. We report fourchildren with dilated coronary arteries and nephro-pathic cystinosis.

Keywords: Nephropathic cystinosis — Coronary ar-tery dilatation — Cardiomyopathy

Cystinosis is an autosomal recessive disorder char-acterized by the excessive accumulation of cystine inseveral organs, including the kidneys, spleen, liver,lymph nodes, cornea, and thyroid gland. Dilatedcardiomyopathy and aortic root aneurysm have beenreported in patients with cystinosis. We report fourpatients with nephropathic cystinosis and dilatedcoronary arteries.

Case Reports

Case 1

A 13-year-old girl presented with chronic renal failure caused by

cystinosis. Cystinosis was diagnosed from renal and bone marrow

biopsies, which were taken in the nephrology department, and

confirmed by opthalmological examination. She was put on a

routine hemodialysis program. Her parents were consanguineous,

and she had two healthy sisters.

A cardiac murmur was found on routine cardiologic exami-

nation, and a chest x-ray revealed cardiomegaly. Echocardio-

graphic examination showed bilateral coronary artery dilatation.

Left coronary artery and right coronary artery diameters were

found to be 4.9 and 4.8 mm (Fig. 1A and 1B), respectively. Bi-

ventricular hypertrophy with a low left ventricular ejection fraction

(58%) was also present.

Case 2

A 9-year-old girl, in whom cystinosis had been diagnosed at 1 year

of age, was admitted. She had experienced severe growth retarda-

tion since the age of 5 months and was found to have hypertension,

hypothyroidism, and proteinuria. The diagnosis was confirmed

from renal and bone marrow biopsies. The patient needed control

hemodialysis twice weekly due to chronic renal insufficiency. She

was the first child of a 37-year-old mother and 50-year-old father.

She had two healthy sisters and a brother. The parents were first

cousins; genetic analysis of the patient found no karyotypic

abnormality.

Echocardiography revealed mild mitral valve insufficiency,

slight tricuspid valve insufficiency, left ventricular dilatation, de-

creased left ventricular ejection fraction (44%), and increased right

ventricular pressure (35 mmHg), estimated from tricuspid valve

regurgitation. Both coronary arteries were dilated. The left coro-

nary artery and right coronary artery diameters were 3.2 and 4.1

mm (Figs. 2A and 2B), respectively. A thallium myocardial per-

fusion scan was normal.

Case 3

An 11-year-old girl with chronic renal failure was admitted to the

nephrology unit suffering from growth retardation, irritability, and

constipation. Nephropathic cystinosis was diagnosed by renal

biopsy, and hemodialysis with medical treatment was started. Her

parents were nonconsanguineous, and no karyotypic abnormality

was found on genetic analysis.

Echocardiography revealed mild mitral and tricuspid valve

insufficiency, left ventricular dilatation, with a left ventricular end

diastolic diameter (LVEDd) of 3.82 mm, a decreased left ventric-

ular ejection fraction (52%), and slightly increased right ventricular

pressure (37 mmHg), estimated from tricuspid valve regurgitation.

Her coronary arteries were found to be dilated. The left coronary

artery and right coronary artery diameters were 4.7 and 3.8 mm

(Figs. 3A and 3B), respectively. A thallium myocardial perfusion

scan was normal.

Case 4

A 9-year-old girl at the time of echocardiography was diagnosed

with cystinosis on the basis of an ocular examination, and the

diagnosis was confirmed by bone marrow and renal biopsies. She

was followed up for approximately 6 years without dialysis, but

after this period of time dialysis was initiated.

Echocardiography revealed slight mitral valve insufficiency,

left ventricular dilatation (LVEDd of 3.69 mm), and a normal left

ventricular ejection fraction (76%). Her left coronary artery and

right coronary artery diameters were 3.6 and 3.2 mm (Figs. 4A and

4B), respectively.Correspondence to: S. Olgar, email: erefolgar@yahoo.com

Pediatr Cardiol 27:263–268, 2006

DOI: 10.1007/s00246-005-1107-0

Case Reports

Discussion

Coronary artery dilatation in adults has been asso-ciated with coronary atherosclerosis, vasculitis(polyarteritis nodosa and Takayasu�s disease), trau-

ma, and hyperlipidemia [1, 8]. There are no reports inthe literature of inherited metabolic diseases associ-ated with coronary artery dilatation.

Cystinosis is inherited in an autosomal recessivemanner and may present as infantile (nephropathic),

Fig. 1. (A) The left coronary artery of case 1. (B) The right coronary artery of case 1.

264 Pediatric Cardiology Vol. 27, No. 2, 2006

adolescent, or adult forms. The infantile, or nephro-pathic, form is the most severe. Chronic renal failuremay develop in patients with nephropathic cystinosisbefore the age of 10 years. The disease is accompa-nied by severe growth retardation [4]. This was ob-

served in our patients, although their mentaldevelopment was normal.

The coronary–aorta index can be used as a quickguide to detect coronary artery dilatation. This index(the ratio of the cotonary artery diameter to the

Fig. 2. (A) The left coronary artery of case 2. (B) The right coronary artery of case 2.

Olgar et al.: Can Cystinosis Cause Coronary Artery Dilatation? 265

aortic annulus diameter) normally falls within anarrow range: 0.15 ± 0.02 for the left coronary ar-tery and 0.13 ± 0.02 for the right coronary artery [7].The normal caliber of coronary arteries, measuredusing the proximal 10 mm of the arteries, is 2 mm ininfants and 5 mm in teenagers [5]. In this study, we

detected that our patients� coronary arteries weredilated by both methods. Coronary artery angio-grams may have helped us to determine the coronaryartery structure. However, we did not perform cor-onary angiograms because there were no symptomsor electrocardiogram (ECG) changes related to cor-

Fig. 3. (A) The left coronary artery of case 3. (B) The right coronary artery of case 3.

266 Pediatric Cardiology Vol. 27, No. 2, 2006

onary ischemia. In addition, thallium myocardialperfusion scans were performed and revealed normalfindings for all patients.

Echocardiography revealed that the coronaryarteries in our patients were wider than normal

(Table 1). The first three patients also had de-creased left ventricular function, and ECGs werenormal.

Myocardial cystine deposition has been reportedin the literature [3]. There is also a report of cardio-

Fig. 4. (A) The left coronary artery of case 4. (B) The right coronary artery of case 4.

Olgar et al.: Can Cystinosis Cause Coronary Artery Dilatation? 267

myopathy caused by cystinosis and dissecting aorticaneurysm in a 7-year-old boy [6].

The most common cause of acquired abnormal-ities of the coronary vessels in children is Kawasaki�sdisease. There were no data indicative of Kawasaki�sdisease in the medical records of our patients.

The myocardium and vessels can be affected bylong-standing hypertension, uraemia, alteredcalcium–phosphorous metabolism due to renalosteodystrophy, large arteriovenous fistulae, renaltransplantation, drugs, and infections [2]. Depressedmyocardial function is a well-known effect of chronicrenal failure. To our knowledge, there is no specificreason why nephritic cystinosis should cause coro-nary artery dilatation. We know of no reportsdescribing coronary arteritis or coronary arterydilatation in patients with cystinosis. It would beinteresting to assess the prevalence of coronary arterydilatation in patients with cystinosis and to collectdata to establish whether the presence of coronaryartery dilatation adversely affects the outcome oftreatment for cystinosis.

Our first three patients had undergone peritonealdialysis or hemodialysis from the time that cystinosisand renal failure were diagnosed. In addition, thesepatients were taking antihypertensives, anticonges-tives (furosemide, captopril, and digitalis), and othermedications (Ca-lactate, phosphorus, vitamin D, L-thyroxine, and cysteamine). In addition to thesedrugs, they were taking anticoagulants (low-molecu-lar-weight heparin) regularly due to their hemodial-ysis arteriovenous fistula. All these factors may havecontributed to the development of coronary arterydilatation. However, the fourth patient had nohistory of anticongestive or L-thyroxine therapy and

did not start dialysis until 6 years after diagnosis. Inthis patient, we believe that cystinosis may have di-rectly affected the coronary arteries. This patient didnot have the renal or thyroid problems that affectedthe other patients.

In summary, we described four patients withnephropathic cystinosis and coronary artery dilata-tion. These findings support reports in the literaturethat cystinosis can affect the vascular system. Patientswith nephropathic cystinosis should be carefullyexamined for coronary artery dilatation.

References

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Table 1. Summary of echocardiographic findings in the four patients

Case

No.

Age

(years)

Weight (kg) Height

(cm)

RCA

(mm)

LCA

(mm)

Aortic annulus

(mm)

RCA/aortic

annulus

LCA aortic

annulus EF (%)

LVEDd

(mm)

1 13 19 104 48 4.9 21.5 0.22 0.22 58 40.9

2 9 19 108 4.1 3.2 21.4 0.19 0.15 44 39.4

3 11 18 102 3.8 4.7 21.9 0.13 0.21 52 38.2

4 9 21 116 3.2 3.6 21.3 0.15 0.17 76 3.69

RCA, right coronary artery; LCA, left coronary artery; EF, Ejection fraction; LVEDd, left ventricular end diastolic diameter.

268 Pediatric Cardiology Vol. 27, No. 2, 2006