There are several renal syndromes with eye changes. Although in many of them, the main ocular lesion is found in the cornea and the lens, in some they are fundoscopic.1-3
Thus, in cystinosis, which consists of a proximal renal tubulopathy and whose manifestations are rickets and a De Toni-Debre-Fanconi Syndrome, cystine deposits are present in the ocular tissues, particularly in conjunctiva and cornea. Pigmentary changes may be observed in the fundus periphery.
This same fundus lesion has been found in Oxalosis and in Senior's Syndrome (Familial Juvenile Nephronophtisis).
In other nephropathies such as Alport's Syndrome, which is characterized by deafness and lens alterations, albipunctatus-like lesions may be observed.
Our attention has been drawn by four children with associated infantile idiopathic hypercalciuria, atypical macular coloboma, and high congenital myopia, when performing systematic surveys at the Department of Nephrology of our center.
The association of these three symptoms, considering the relative low frequency of «nfantile idiopathic hypercalciuria and of the so-called "macular coloboma, has made us think of the possibility of a new oculo-renal syndrome. Reviewing the literature, we have only found one publication J with two similar cases in brothers.
CASE 1 - E.G.S.
This 10-year-old boy, weight 24.4 kg and height 1.29 meters, was seen because of growth delay, polyuria polydipsia. Radiology: Nephrocalcinosis. Creatinine Clearance: 79 ml/min/1,73 mp 2. Normal bicarbonate excretion threshold and ammonium chloride acid overload test. Maximum urinary osmolality: 483m0sm/kg. Calciuria in basal conditions: 23 mg/kg/day, not modified with sodium bicarbonate intake; with hyposodic diet and/or hydrochlorothiazide it decreases to normal values (1.4 mg/kg/day).
FIGURE 1: Case 1, r.e.; Posterior pole hypopigmentation with diminished choroidal vascularization.
FIGURE 2: Case 1, I.e.; chorioretinal atrophy area of 2 disc diameters surrounded by pigment. Hypopigmentation and choroidal hypovascularization.
FIGURES 3 & 4: Case 2, o.u.; posterior pole chorioretinal atrophy area of 3-4 disc diameters, surrounded by pigment. Posterior pole hypopigmentation and choroidal hypovascularization.
Absence of other tubular functional disorders. Infantile idiopathic hypercalciuria is thus confirmed.
Eye examination: visual acuity: r.e.: (-1 2.00 -2.00 60″) = 20/30; I.e.: (-10.00 -2.00 120″) = 20/400. Fundus: o.u.: macular area hypopigmentation with ratified choroidal but normal retinal vessels (Figure 1); I.e.: 2 disc diameter chorioretinal atrophic area with pigmented sharp edges with a macular coloboma appearance (Figure 2). ERG: normal in right eye and slightly subnormal for red and blue stimuli in left eye. Normal toxoplasmosis, cytomegalovirus, rubella, and syphilis serology.
CASE 2 - A.G.S.
This five-year-old girl, a sister of Case 1. weight 17.2kg and height 1.04 meters, was seen because of polyuria and polydipsia. Radiology: Nephrocalcinosis. Creatinine Clearance: 64ml/min/1.73 m . Normal bicarbonate excretion threshold and ammonium chloride acid overload test. Maximum urinary osmolality: 406 m0sm/kg. Calciuria in basal conditions: 30 mg/kg/day. This value is not modified by sodium bicarbonate intake; however, with a hyposodic diet and/or hydrochlorothiazide it decreases to normal values (0.5 mg/kg/day). Infantile idiopathic hypercalciuria is hence established.
FIGURES 5 & 6: Case 3. o.u.; chorioretinal atrophy area of 4 disc diameters with pigmentation mainly at the edges. Hyperpigmented fundus.
FIGURE 7: Case 4 r.e.; posterior pole hypopigmentation with choroidal hypovascularization.
Eye examination: visual acuity: o.u.: (-10.00) = 20/400. Fundus: o.u.: total chorioretinal atrophic area of 3-4 disc diameters in the posterior pole with sharp pigmented edges and no retinal or choroidal vessels. The rest of the posterior pole is hypopigmented with visibility of gross choroidal vessels in some parts and absence of them in others. ERG: slight amplitude lessening for all stimuli in right eye and only for red stimuli in left eye. Negative toxoplasmosis, cytomegalovirus, rubella and syphilis serology (Figures 3 & 4).
CASE 3 - F.P.S.
This 9-year-old boy, weight 21.2 kg and height 1.22 meters, was seen because of polyuria, polydipsia, and nephritic colic. Radiology: Nephrocalcinosis, renal lithiasis. Creatinine Clearance: 108ml/min/1.73nv. Normal acid-base equilibrium. Normal bicarbonate excretion threshold and ammonium chloride acid overload test. Maximum urinary osmolality: 440 mOsm/kg. Calciuria in basal conditions: 28 mg/kg/day, not modified with bicarbonate intake; however, it decreases to normal values (2.7 mg/kg/day) during hyposodic diet and/or hydrochlorothiazide treatment. Absence of any other tubular disorders. Infantile idiopathic hypercalciuria is thus confirmed.
FIGURE 8: Case 4, I.e.; chorioretinal atrophy area which occupies the entire macular area. Pigment accumulation at the edges.
FIGURE 9: Disc coloboma, inferior chorioretinal coloboma and macular coloboma. Contralateral eye has an iris coloboma in addition to the previous disorders.
Eye examination: o.u.: (-10.00 -3.00 180") = handmovement vision. Fundus: o.u.: posterior pole chorioretinal atrophic area of 4 disc diameters with pigmented edges and normal retinal vessels ERG: normal. The rest of the fundus is hyperpigmented. (Figures 5 & 6). Negative toxoplasmosis, cytomegalovirus, rubella and syphilis serology.
CASE 4 - V.A.L.
This 13-year-old girl, weight 41 kg, height 1.48 meters, was admitted to our center for renal lithiasis surgery. Radiology: Nephrocalcinosis and bilateral renal lithiasis. Creatinine Clearance: 35ml/min/1.73 m'. Normal bicarbonate excretion threshold and ammonium chloride acid overload test. Maximum urinary osmolarity: 250 m0sm/kg. Calciuria in basal conditions: 20 mg/kg/day. This value is not modified by sodium bicarbonate intake; however, with hyposodic diet and/or hydrochlorothiazide treatment it decreases to normal values (3.5 mg/kg/day). There are no other tubular functional disorders. Infantile idiopathic hypercalciuria is thus confirmed.
Eye examination: visual acuity: r.e.: (-1 1.00 -3.00 30″) = 20/30; I.e.: (-11-00 -1.00 180″) = hand-movement vision. Fundus: As in Cases 1 and 2, there is posterior ,pole hypopigmentation and visibility of choroidal vessels, which are diminished in some areas, in both eyes; I.e.: there is a chorioretinal atrophic area with sharp edges and surrounded by pigmentation, which occupies the posterior pole between the inferior and superior temporal vascular arcades (Figures 7& 8). ERG: normal. Negative toxoplasmosis, cytomegalovirus, rubella, and syphilis serology.
Infantile Idiopathic Hypercalciuria: The term idiopathic hypercalciuria means an excessive loss of calcium through the urine with normal calcemia. Hypercalciuria is diagnosed when calcium renal excretion exceeds 6-8 mg/kg/day.
Idiopathic hypercalciuria is more frequent in adults than in children. In the latter, there is one benign picture similar to the adults which is only associated with renal lithiasis, and another more severe picture described by Royer in 1962,1 which is the one we are concerned with and which is associated with dwarfism, osteoporosis, delayed bone maturation, nephrocalcinosis, lithiasis, urine concentration defect (hypostenuria), polyuria, tubular proteinuria in half of the cases, phosphates tubular reabsorption coefficient decrease, and normal tubular regulation of acid-base balance.
Under pathological examination, kidneys may either be normal or present an interstitial nephritis with nephrocalcinosis.
It should be stressed that calciuria does not increase with vitamin D nor does it increase with sodium bicarbonate intake, unlike what happens with idiopathic chronic tubular acidosis (Albright's syndrome). Moreover, it is not modified by calcitonin injection, yet it does diminish by means of calcium and sodium chloride deficient diet, sodium phytate, hydrochlorothiazide, and phosphorus overloading.
In regard to the infantile idiopathic hypercalciuria physiopathology, the excessive amounts of calcium in urine account for the urinary concentration disorders, the proteinuria, lithiasis, and nephrocalcinosis as well as for a negative calcium balance which is associated with dwarfism, delayed bone maturation, and osteoporosis.
Infantile idiopathic hypercalciuria is a relatively rare syndrome. Thus, in 1975, Royer," 13 years after its description, presents a series of only ten cases. The nephrology department at our center has diagnosed five cases, of which four are described in this study.
Macular Coloboma: Considering the fact that we are dealing with an ophthalmoscopic change, we shall be interested mainly in its etiopathogenesis.
Before 1940, when toxoplasmosis was completely unknown, all macular congenital chorioretinitis was thought to be a macular coloboma, including the cases of still undiagnosed systemic toxoplasmosis. In subsequent revisions, when the toxoplasmosis serological diagnosis as well as the entire clinical picture of the embryopathy caused by this parasite were already known, it was found that many of the cases diagnosed as "macular coloboma" were in fact cicatricial fetal chorioretinitis and were thereafter called "inflammatory macular pseudocolobomas."
Moreover, it was found that apart from toxoplasmosis, other infectious embryopathies, particularly viral ones such as cytomegalovirus, were able to cause the same macular pseudocoloboma picture.
In spite of this, new cases keep on showing up, some of which are described in the literature, such as those referred to in Miller and Bresnick's work, where bilateral macular colobomas with familial incidence are described, in many cases associated with systemic malformations" or other ocular malformations such as chorioretinal typical coloboma or disc coloboma (Figure 9). In these cases it is obviously very difficult to subscribe to the inflammatory theory.
It would perhaps not be so accurate to talk about macular coloboma since coloboma is a fetal fissure closure fault and the macula is not included in this zone. It would therefore be more appropriate to call it macular agenesia or aplasia.
In our four cases, the possibility of an embryopathy due to toxoplasmosis, rubella, cytomegalovirus, or syphilis was eliminated because of negative serologies and absence of a systemic clinical picture. It should be stressed once again that two of the cases were brothers, but in the remaining cases there was no consanguinity nor any ocular or renal illness family background.
The dystrophic character of these lesions is not probable due to the asymmetry of Cases 1 and 4, which are unilateral. Furthermore, they do not present peripheral predominance and a late manifestation in life as some dystrophies do (e.g., atrophia girata, choroideremia). The ERG was slightly subnormal in the first two cases, but there was no photophobia, hemeralopia, color vision or pigmentary changes in any of the cases. However, in one of the two cases described by Meier, there were peripheral pigmentary changes and altered scotopic ERG.
High Congenital Myopia: Congenital axial pathological myopia is much less frequent than simple or evolutive malignant myopia. Congenital myopia, generally higher than 6 diopters, is not progressive.
It is frequently associated with other congenital disorders such as colobomas, although they do not present scleral ectasia. It may also appear with chorioretinal dystrophies.
The fundus of high congenital myopia often presents choroidal and retinal pigmentary abnormalities of two sorts:
* uniform hyperpigmentation
* albinism-like hypopigmentation. Albinism is, on the other hand, often accompanied by myopia.
1. Edwards WC, Sondreson-Grizzard W: Tapetoretinal degeneration associated with renal disease. J Ped Ophthalmol Strabismus 1981; 18:55-57.
2. Van Balen AT, Van Collenburg JJ: Tapetoretinal degeneration and familial juvenile nephronophthisis. J Ped Ophthalmol Strabismus 1976; 13:329-335.
3. Fontaine JL, Boulesteix J, Saraux H, et al: Nephropathie tubulo-interstitielle de l'enfant avec degenerescence tapetoretinienne. Arch Fr Pediatr 1970; 27:459-470.
4. Meier W, Blumberg A, Imahorn F, et al: Idiopathic hypercalciuria with bilateral macular colobomata: A new variant of oculo-renal syndrome. HeIv Paediatr Acta 1979; 34:257-269.
5. Royer P, Habib R, Mathieu H: Problèmes Actueles de Nephrologie Infantile. Paris, Flammarion, 1963, p 57-60.
6. Royer P, Habib R, Mathieu H, et al: Nephrologie Pediatrique. Paris, Flammarion, 1975, p 61-64.
7. Miller SA, Bresnick G: Familial bilateral macular colobomata. Brit J Ophthalmol 1978; 62:261-264.
8. Phillips CI, Griffiths DL: Macular coloboma and skeletal abnormality. Brit J Ophthalmol 1969; 53:346-349.