Cystine Storage Disease with Aminoaciduria and Dwarfism (LIGNAC—FANCONI DISEASE): INTRODUCTION

Abstract

Summary Fourteen children suffering from cystine storage disease with aminoaciduria (Lignac‐Fanconi disease) have been studied i n the last 3 years, and the results are described in a series of eight papers of which this first paper contains a short review of the literature, some general remarks on aminoaciduria, cystinuria and cystine storage, and a brief statement on some of the results obtained and conclusions reached. Publications by Lignac, Fanconi, Beuiner and Wepler, and others, as well as our own observations, lead us t o the conclusion that Lignac's disease (cystine storage disease) and Fanconi's syndrome of childhood (nephrotic glycosuric dwarfism) are one and the same disease. At the present time this disease cannot be identified with similar syndromes in which cystine storage has been excluded. The variability of nearly every symptom in Lignac‐Fanconi disease is stressed. The most reliable diagnostic features besides dwarfing are cys tine storage and aminoaciduria of a characteristic pattern. Cystine storage can be demonstrated in vivo by slit‐lamp investigation in cornea and conjunctiva, as well as in bone marrow and lymph glands, and the cystine can be identified in biopsy material by microscopy, X‐ray crystallography and chromatography. The aminoaciduria is accompanied by aminoacidaemia, and the characteristic pattern in urine is best shown by paper chromatography. The differentiation from other forms of aminoaciduria, such as that of newborn infants and classical cystinuria, is discussed. Reasons are given why cystine storage and aminoaciduria are regarded as the result not of kidney dysfunction but of a prerenal disturbance of the whole aminoacid metabolism, probably situated within the reticulo‐endothelial system.

Transport and Intracellular Fate of Cysteine-35S in Leukocytes from Normal Subjects and Patients with Cystinosis

“…We have recently found eighty times as much free-cystine in cystinotic as compared The basic defect in metabolism leading to the formawith normal leukocytes [23]. This fact, coupled with tion of cystine crystals in the rare inherited disease, the normal plasma concentration of cystine found in cystinosis, is not known [2,27,30]. The cystine is these children [4], suggested a defect in the transport thought to cause both the renal tubular defects of the of cyst(e)ine (cystine and/or cysteine) in cystinotic Fanconi syndrome which appear during the first year of cells, analogous to the apparent defect in cystine translife, and the progressive renal glomerular damage which port in cells of the renal tubules in the otherwise unleads to death of affected children [12,20].…”

“…Correction has been made for the cysteine- 35 S which remains attached to the thiolated sephadex. 2 Compounds which elute very near the solvent front and are not separated from each other by the method used. 3 Mean ± 1 SD.…”