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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.

THE subjects of this investigation are sisters, one of whom, the younger, was first referred to the Birmingham Children's Hospital by Dr Burns of Redditch for the investigation of albuminuria. She was admitted and on examination was found to have cystinuria. A subsequent examination of a specimen of urine from the sister revealed cystine crystals and she, also, was admitted for investigation and observations on metabolism. Family history. Cystinuria is one of a group of disorders which have been aptly described by Sir Archibald Garrod in the picturesque phrase "inborn errors of metabolism". An enquiry was instituted, therefore, into the occurrence of the derangement in other members of the family, and with the cooperation of the patients' doctor and parents many specimens of urine were collected from each of seventeen blood relatives, at intervals of several weeks, and examined by us for cystine. The tests applied were: (1) Microscopical examination of sediment: (a) from the fresh specimen, (b) after acidifying with dilute acetic acid and standing for one week, and (c) from acidified specimens concentrated by evaporation. (2) The Sullivan reaction as modified by Brand et al. [1930]. (3) The cyanide-nitroprusside reaction described by the same authors. These investigations revealed well-marked cystinuria in one other relative, whose 358 E. M. HICKMANS AND W. C. SMALLWOOD These findings, together with the results of tests for albumin and estimations of total amino-acids, appear in Table I. It will be seen that the presence of traces of cystine in the urine of one individual was not constant and that specimens in which, on microscopy, two or three hexagonal crystals were found did not always yield positive chemical tests and vice versa. Various writers [Loewy and Neuberg, 1907; Lewis and Simon, 1902] have suggested that the degree of cystinuria may vary considerably from time to time and even disappear temporarily. At first we were tempted to believe that these other members of the family were occasional or mild cystinurics and that the union of two such individuals had resulted in two florid examples of the metabolic error. We do not feel justified, however, in advancing this thesis on such slender evidence. There was no consanguinity of parentage in any of the families and no family history of stone or of nephritis known to the parents of the two children investigated. Clinical history. W.B. Aged 12 years. First child in family of two. Admitted to Birmingham Children's Hospital on April 26th, 1932. History. Quite well until 6 months previously; since then vaguely unwell; easily tired, frequently complaining of backache referred to both loins and relieved by lying down. For 3 months prior to admission scalding micturition but no increased frequency of micturition or other urinary symptoms. Occasional headaches for many years. Examination. A tall slender girl: weight 5 stone 6 pounds: nutrition moderately good and general appearance one of health. Mentality normal. No abnormality of cardiovascular, respiratory, alim...

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