Reporte de un caso de Cistinuria: Uso de herramientas de diagnóstico a nivel nacional / Report of a case of cystinuria: Use of diagnostic tools at national level

La cistinuria es una enfermedad genética que se engloba dentro de alteraciones congénitas del transporte de aminoácidos con formación de cálculos en las vías urinarias, si bien es poco frecuente se caracteriza por su elevada recurrencia. En este trabajo presentamos el caso de una paciente de 34 años, con antecedentes de haber perdido un riñón por episodios anteriores de litiasis y con múltiples recidivas que es diagnosticada mediante la detección de cistina por espectroscopía infrarroja como componente único de 96 fragmentos de cálculos removidos mediante nefrolitotomía percutánea. La paciente fue evaluada laboratorialmente mediante el perfil metabólico y la cristaluria. Las indicaciones de tratamiento específicas incluyeron la administración de agentes alcalinizantes, régimen nutricional, y entrenamiento para control de pH urinario. Es importante señalar la agresividad de la litiasis de cistina con las consecuencias que puede tener la calidad de vida del paciente, y por tanto la importancia de contar con capacidades instaladas a nivel país para el diagnóstico y seguimiento de litiasis genéticas como la causada por la cistinuria(AU)

Cystinuria is a genetic disease that is included among congenital defects of renal amino acids transport that causes urinary stone formation. Although it is rare, it is characterized by its high recurrence. We present the case of a 34-year-old patient that lost one of her kidney because of recurrent episodes of lithiasis, and that was diagnosed by the detection of cystine with infrared spectroscopy as the sole component of 96 stone fragments removed by percutaneous nephrolithotomy. The patient was evaluated by metabolic profile and crystalluria. The specific treatment indications included the administration of alkalinizing agents, nutritional regimen, and training for personal measurement of urinary pH. This case highlights the aggressiveness of cystine stones with the consequences that may have on the quality of the patient life, and therefore the importance of having installed proper diagnostic capacities at national level to detect and monitor treatment efficacy in genetic lithiasis such as cystinuria(AU)

Cuantificación de cistina en orina espontánea para la detección de cistinuria / Quantitation of urinary cystine for the detection of cystinuria / Determinagáo quantitativa de cistina urinaria para a detecgáo de cistinuria

La cistinuria es un error innato del metabolismo ocasionado por un defecto en el transporte renal de arginina, ornitina, lisina y cistina. La acumulación de este último aminoácido de baja solubilidad ocasiona episodios de urolitiasis característicos de la enfermedad. En el presente estudio se estandarizó un método espectrofotométrico confiable y de fácil ejecución para la determinación cuantitativa de cistina en orina espontánea. Se realizó el análisis en 184 muestras, correspondientes a 104 controles y 80 pacientes con urolitiasis. Con el objeto de validar el método y posteriormente establecer un rango de excreción normal en la población colombiana se evaluaron los siguientes parámetros: exactitud, precisión, linealidad y límite de detección. La técnica mostró coeficientes de variación intra e inter ensayos inferiores al 10% y una excelente linealidad, con un coeficiente r² entre concentraciones conocidas de cistina y absorbancia generada por el método de 0,998. Usando esta técnica se encontró un valor normal de excreción de 1,35 a 110,11 mg cistina/g creatinina. En cinco pacientes, de los 80 con nefrolitiasis, se hallaron valores elevados de cistina, compatibles con cistinuria. El método utilizado puede implementarse en cualquier laboratorio clínico para confirmar el diagnóstico de cistinuria e iniciar un tratamiento oportuno.

Cystinuria is an inborn error of metabolism, caused by a defect in renal tubular transport of the following aminoacids: arginine, ornithine, lysine and cystine. Accumulation of the latter poorly soluble aminoacid leads to the development of kidney stones, characteristic of the disease. In this study, an easy and dependable spectrophotometric method for the quantitative determination of urinary cystine was standardized. The analysis was performed on 184 samples from 104 controls and 80 patients with kidney stones. In order to validate the method and later establish a range of normal urinary cystine excretion in the Colombian population, the following parameters were evaluated: Accuracy, precision, linearity and lower limit of detection. The technique showed intra and intei assay coefficients of variation below 10%, and excellent linearity, with an R square (r²) coefficient between known cystine concentrations and absorbance generated by the method at 0.998. Using this technique, a normal urinary cystine excretion range of 1.35-110.11 mg cystine/g creatinine was found. Among the 80 patients with kidney stones, elevated urinary cystine levels were found in 5 of them, compatible with the presence of cystinuria. This method can be implemented in any clinical laboratory to confirm the diagnosis of cystinuria and provide opportune treatment.

A cistinúria é um erro inato do metabolismo, causado por um defeito no transporte tubular renal de ar-ginina, ornitina, lisina e cistina. A acumulagáo deste último aminoácido, pouco solúvel, provoca episodios de urolitíase, característicos da doenga. No presente estudo, foi padronizado um método espectrofotomé-trico confiável e de fácil execugáo para a determinagáo quantitativa de cistina em urina espontánea. A análise foi realizada em 184 amostras de 104 controles e 80 pacientes com urolitíase. A fim de validar o método e, posteriormente, estabelecer um intervalo de excregao normal na populagao colombiana, foram avaliados os seguintes parámetros: exatidáo, precisáo, linearidade e limite inferior de detecgáo. O método mostrou coeficientes de variagáo intra e inter ensaios inferiores a 10%, e excelente linearidade, com um coeficiente R quadrado (r²) entre concentragoes conhecidas de cistina e absorváncia gerada pelo método de 0,998. Com esta técnica, foi encontrado um valor normal de excregáo de 1,35-110,11 mg cistina/g de creatinina. Entre os 80 pacientes com urolitíase, foram encontrados níveis elevados de cistina em cinco deles, compatíveis com a presenga de cistinúria. Este método pode ser implementado em qualquer laboratorio clínico para confirmar o diagnóstico de cistinúria e proporcionar um tratamento oportuno.

Hyperlysinemia with saccharopinuria due to combined lysine-ketoglutarate reductase and saccharopine dehydrogenase deficiencies presenting as cystinuria.

A 7-year-old boy with speech delay, hyperactive behavior, and minor neurologic abnormalities had been found in the past to have "intermittent cystinuria." A more detailed investigation revealed hyperlysinemia and hyperlysinuria, with lesser increases in urinary excretion of arginine and cystine. The plasma and urine abnormalities increased on a diet of 3 gm of protein/kg body weight/day. Saccharopine, a normal metabolite of lysine not found in the body fluids of normal people, was present in plasma, cerebrospinal fluid, and urine of the patient. Lysine-ketoglutarate reductase and saccharopine dehydrogenase activities were not detectable in extracts of cultured skin fibroblasts. Re-examination of the urine of previously studied cases of this double enzyme deficiency suggests that saccharopinuria of variable degree is the rule and not the exception.

[Cystinolysinuric lithiasis]. / Litiásis cistinolisinúrica.

Cystinuria is a disease characterized by the excessive elimination of cystine and of dibasic amino acids (lysine, arginine, and ornithine) through urine of homozygotes. This study included 6 children complaining of abdominal pain with or without hematuria. The existence of renal radio-opaque lithiasis was confirmed in 5 of them and in the sixth, it was vesical. The clinical and analytic data were practically normal with the exception of the qualitative test of the amino acid urinary excretion that showed increase in urinary excretion of cystine. Likewise, percentages of tubular reabsorption were pathological in all the patients showing values between 35.4% and 74%. The diagnosis of systini-lysinuric lithiasis was established through amino acid excretion study in the six patients which was below normal; it fluctuated between 36% and 74%. Lysine, together with cystine, was the most frequently affected.