Orange-colored diapers as first sign of Lesch-Nyhan disease in an asymptomatic infant

Abstract

Sirs, We read with great interest the letter of Demirdas and Schroder [1] about the differential diagnosis in changed color of urine in infants. We have followed a 3-month-old male who was hospitalized for the presence of orange-colored diapers. He was born from unrelated parents after an uneventful pregnancy. High levels of uric acid were found in the plasma (11.7 mg/dl; normal values 1.7–5.8). Kidney ultrasound examination showed mild and diffuse increase of signal in cortical area with nephrolithiasis. Fundus oculi, electroencephalogram (EEG), and brain ultrasound were normal. Successively, the infant presented dystonic movements, mild axial hypotonia, and hypertonia of the legs with increased tendon reflexes and scissoring. The study of purine and pyrimidine metabolism by electrospray ionization tandem mass spectrometry (MS-MS) showed high levels of hypoxanthine (20.3 mmol/mol of creatinine; normal values 0.43–11.31). Enzymatic assay in red cells showed an absence of hypoxanthine-guanine phosphoribosyltransferase activity (HGPRT). Molecular analysis confirmed the diagnosis of Lesch-Nyhan disease (LND; OMIM 300322) in the patient and his mother as a carrier: a duplication of 8 nucleotides 89–96 (89_96dupAGGATTTG) in exon 2 of HPRT1 gene was found in chromosome X. Brain magnetic resonance imaging showed white matter atrophy of bilateral symmetric temporal-insular regions with respective enlargement of subarachnoid spaces with mild decreased concentration of NAA and Cho at spectroscopy. At 20 months, the patient was unable to control his head or speak; he also showed swallowing and severe dystonic-dyskinetic movement disorder of the upper limbs with generalized hypertonia crisis towards opistotonus. LND is a rare X-linked recessive disorder [2] characterized by the progressive development of mental retardation, spasticity, choreo-athetosis, self-mutilation, and hyperuricemia [3, 4], due to complete deficiency of the activity of HGPRT (OMIM 308000) [2]. However, partially HGPRTdeficient patients (OMIM 300323) present these symptoms with different degrees of intensity [5]. In these patients, orange crystals may be identified in diapers during the first weeks of life, but only rarely are they an early sign of the disease [3, 4, 6]. For example, Jinnah et al. [7] reported only one patient in 40 with LND. Orange crystals are often present in diapers during the first weeks of life, when deposits of pink or red uric acid crystals are observable [8]. Urate crystals are orange-red precipitates formed in the bladder, which look like ‘brick dust’ in a diaper [1]. Notwithstanding, orange-colored urine could be due to a variety of causes. The commonest is due to some food colors such as phenolphthalein or beet, drugs S. Gasperini : R. Guerrini :G. la Marca :M. A. Donati Department of Pharmacology, University of Florence, Florence, Italy