Characterization of carrier females and affected males with X-linked recessive nephrolithiasis.

X-linked recessive nephrolithiasis (XRN) was described in a large kindred in which nephrolithiasis; proximal tubular dysfunction, proteinuria, nephrocalcinosis, and renal failure occur only in males. Carrier females are asymptomatic, but formal studies of them have not been done. The gene for XRN has been mapped to the pericentromeric region of the X chromosome, close to the loci for several eye disease genes. We studied six affected males, 13 carrier females, and 25 normal members of this family including 7 females whose genetic haplotype predicted them to be carriers. Studies were done in the Clinical Research Unit on a diet containing 400 mg of calcium and 2 g of sodium, and by an additional outpatient urine collection was obtained on a 1-g calcium intake. Hypercalciuria occurred in five of six affected males, 4 of 12 carrier females, and three of seven predicted carriers. Significant proteinuria was present in all affected males and in no other subjects. Low-molecular-weight proteinuria was present in all affected males: the excretion of alpha 1-microglobulin exceeded normal by 3- to 14-fold, of beta 2-microglobulin exceeded normal by 100- to 400-fold, and of retinol-binding protein exceeded normal by 1,000- to 3,000-fold. The excretion of these proteins was less strikingly elevated in carrier females, but the excretion of alpha 1-microglobulin was abnormal in 9 of 15 carriers, beta 2-microglobulin was abnormal in 12 of 15, and retinolbinding protein in was abnormal 12 of 13, and this pattern was similar in predicted carriers. The urinary concentrating ability was abnormal in four affected males with renal insufficiency but normal in all other subjects. Urinary wasting of potassium, phosphorous, and glucose occurred infrequently, and no subject was hypouricemic. Formal ophthalmologic studies were normal in five affected males. Thus, the most consistent urinary abnormalities in XRN are hypercalciuria and low-molecular-weight proteinuria, the latter of which appears to be a marker for the carrier state.

Pseudoexfoliative fibrillopathy in the skin of patients with ocular pseudoexfoliation.

In addition to its occurrence within the eye, pseudoexfoliative fibrillopathy has been reported in the conjunctiva and around a posterior ciliary artery. To determine whether it has a more diffuse extraocular distribution, we studied skin biopsy specimens ultrastructurally from one to three areas in 13 patients with classic pseudoexfoliation. A fibrillopathy closely resembling that in the eye was found in 11 of the 13 patients. Only one of the 13 control subjects, a 78-year-old man with advanced low-tension glaucoma, had a similar fibrillopathy. In the patients with pseudoexfoliation who were more than 70 years of age, the accompanying dermal elastosis made evaluation difficult, because the pseudoexfoliative nodules in the skin occur primarily along elastic fibers, and their morphologic characteristics appeared to be influenced by the elastotic process. These results suggest that pseudoexfoliation is a systemic process related closely to elastosis, and that further search for pseudoexfoliative fibers should be made in the elastic system of the deep tissues and internal organs.

Localized conjunctival amyloidosis associated with extranodal lymphoma.

A 62-year-old man was found to have a large asymptomatic amyloid nodule of the conjunctiva. Within the next year, a diffuse mixed small and large cell lymphoma of his scapula developed with amyloid in its stroma. No abnormal serum or urine protein was found. Subsequently, rib and paraspinal masses appeared. After irradiation and chemotherapy, the patient died of bronchopneumonia, 3 years after onset. By immunostaining, the amyloid of both conjunctiva and scapular tumor was of polyclonal immunoglobulin (AL) type, most prominently IgG and lambda chains, with lesser staining for IgA and kappa chains. The tumor cells showed a similar pattern. To our knowledge, this is the first report of systemic lymphoma and localized conjunctival amyloidosis without a serum paraprotein, and the first such association with a lymphoma of this cell type. Immunotyping of conjunctival amyloidosis should be performed to guide the workup for possible systemic disease.

Pseudomelanoma of the iris in herpes simplex keratoiritis.

A 37-year-old white man with a long history of recurrent herpetic keratitis presented with a rapidly enlarging pigmented iris lesion. The primary diagnostic concern was that the lesion might be a malignant melanoma. A biopsy of the mass was done and proved it to be a granuloma with granulomatous arteritis and infarction of the iris. In a patient with a history of recurrent ocular inflammation, such a hypersensitivity granuloma should be considered in the differential diagnosis of iris melanoma.