Negative Urine Benedict’s Test in a Child with Galactosemia: A Diagnostic Challenge

To the Editor: Incidence of galactosemia in India is reported as 1:10,300 [1]. In resource limited settings, a case of neonatal liver failure is often screened for galactosemia using urine Benedict’s test.We report a case of galactosemia with negative urine Benedict’s test. A 16-d-old female infant was admitted with jaundice, vomiting, breathing difficulty and fever of 7d duration. She was on exclusive breast-feeding. On examination she had icterus with firm non-tender hepato-splenomegaly. At admission she had unconjugated hyperbilirubinemia, which in a few days changed to high conjugated fraction. Blood sugar, sepsis screen, complete blood counts, thyroid profile and serum ferritin were normal. Ophthalmological examination was normal and urine reducing substance by both clinistix and Benedict’s test were negative on 2 occasions. Ultrasound abdomen showed features suggestive of parenchymal liver disease. Tandem mass spectrometry and urine GCMS were normal. Hence liver biopsy was also done which showed macrovesicular steatosis, canalicular cholestasis, widened portal tracts with infiltration by lymphocytes and few neutrophils. After 12d of admission, she developed features of worsening liver cell failure and repeat urine Benedict’s was now positive. As a definite diagnosis was not available and she was rapidly deteriorating, empirically lactose free soy based formula was started after which she improved. Her total blood galactose level obtained subsequently was 504-mg% (normal < 15 mg%). GALT enzyme activity was < 0.04 units/g Hb (Normal 1.0–5.0 units/g Hb). Currently at 9mo of age, on a lactose free diet she is thriving well. Galactosemia is a disease which if picked up early is rarely fatal because the liver dysfunction is reversible. Screening is often done by urine Benedict’s test. Diagnosis is made based on elevated blood galactose levels, the RBC galactose1-phosphate level and urine galactitol levels. In our case, delay in diagnosis was because of serial initial false negative urine Benedict’s test. Urine Benedict’s test is reported to have high false positive rate and almost no false negatives [2]. However in our case, initial Benedict’s test was negative twice even when the child was on breast feeds, followed by a positive result only after the onset of hepatic failure. The initial negative result is probably attributable to moderate metabolite elevation, which is described in heterozygous GALT mutation [3]. In a resource limited setting like ours it is often not possible to send blood galactose or enzyme levels due to financial or logistic constraints and screening for galactosemia is done by urine Benedict’s test. Cell-based galactosemia diagnosis system based on a galactose assay using a bioluminescent Escherichia coli array is a novel method of screening [4]. As galactosemia is a condition amenable to treatment, we suggest that it is worthwhile repeating the urine Benedict’s test on multiple occasions and giving a trial of lactose free formula in suspected cases.