Galactosaemia – The Cause of Gram Negative Neonatal Sepsis

Galactosaemia is caused by deficiency of the enzyme galactose1-phosphate uridyltransferase (GALT). Gram negative sepsis, liver failure and death are common if untreated. Early diagnosis especially in babies with Gram negative sepsis can prevent both morbidity and mortality.


Introduction
Galactosaemia [1], a genetic deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT), causes accumulation of galactose, galactose-1-phosphate and galactitol in tissues of affected individuals [1]. The primary source of galactose is lactose, in milk. The clinical signs of this defect (feeding problems, hepatomegaly, jaundice, failure to thrive, cataracts, hypoglycaemia, gram negative sepsis and acute liver failure) [1,2] may become evident during neonatal period and result in death [3].
Galactosaemia can be diagnosed by newborn screening [1]. With restriction on galactose intake -the disease progress can be prevented. India lacks the universal newborn screening program. Thus Paediatricians need to actively seek diagnosis and provide treatment thereafter.
We report 2 cases of galactosaemia presenting with recurrent gram negative septicaemia in early life but were not diagnosed till late.

Case 1
An ex-preterm male baby born at 28 weeks, with 850 grams birth weight presented to us at a corrected age (CA) 42 weeks with failure to thrive. Weight on admission was 1450 grams, below the 10 th centile on Fenton's growth chart. Baby had required intensive care involving ventilation, surfactant administration, total parenteral nutrition, and prolonged antibiotics for gram negative septicaemia on 2 occasions, first one due to E.Coli and second one due to Gram Negative Bacilli, in the neonatal period. He had been discharged on full enteral feeds at CA 36/40 with a discharge weight of 1600 grams. Two weeks later -he was readmitted -when he had abnormal liver function test with deranged enzymes and a bilirubin of 15 gms/dLwith direct components of 10 mg/dLmg/dl. He had been investigated with HIDA scan for Biliary atresia & congenial infections in the form of TORCH screen. The ultrasonography of abdomen, HIDA scans& TORCH serology were all normal. On this admission, baby presented with failure to thrive and features of sepsis, was started on broad spectrum antibiotics. Initial septic screen suggested high C-reactive protein 86 mg/dl (N= <6mg/dl) and blood culture grew Esciheria Coli. Urine and CSF cultures were sterile. Baby was positive for Galactosemia. Despite all efforts, baby succumbed on 5 th day to fulminant sepsis and coagulopathy.

Case 2
A 4 1/2 month old female child admitted with signs of sepsis and failure to thrive. She was a term baby with a birth weight of 3.1 Kgs and had a normal neonatal course. She was discharged on breast feeds, until she presented to a referring paediatrician for failure to thrive on breast feeds. Initial investigation showed persistent hyper-bilrubinemia of 13 mg/dl with direct bilirubin of 9 mg/dl and so was investigated for sepsis, congenital infections, biliary atresia and Tuberculosis. The septic screen was positive for Escheriacoli, hence the baby also had lumbar puncture and was discharged later on breast feeds. As part of the investigations, she has had newborn screening by tandem mass spectrometry (TMS), which was positive for Tyrsoinemia, later confirmed to be false positive& was suggestive of transient tyrosinaemia. On this admission, baby had septic screen, along with metabolic screen involving serum lactate, ammonia, and liver & renal function tests with test for Galactosemia& Cystic Fibrosis. The septic screen came positive for Pseudomonas aeruginosa and high CRP of 186mg/dl. Urine and CSF cultures were sterile. The infant succumbed on day 6 th of admission to fulminant sepsis with coagulopathy. Galactosemia screening was positive.

Discussion
In the above two cases, we demonstrate infant deaths for lack of early diagnosis of a treat able disease. Both the babies had recurrent episodes of gram negative sepsis with persistent hyper-bilirubinemia, and failure to thrive. But the possibility of galactosemia was not thought of nor investigated. In the second case, baby did have a metabolic screening in the form of TMS but not galactosaemia. India does not have newborn screening program, laboratories have to be specifically instructed. Paediatricians request TMS for Inborn Errors of Metabolism (IEM) screen, but TMS does not screen galactosemia [6]. TMS is useful for diagnosing disorders of Amino acid, Organic acid and fatty acid metabolism [6]. Galactosemia is screened using mono-analyte method on chromatography (fluorescent galactose oxidase method) [7], which measures GALT/ GPUT enzyme on blood spot collected on filter paper. If screen levels show low transferase activity, prompt confirmation with quantitative study of enzyme are done. Hence unless specifically requested, IEM screen by TMS will not screen for galactosemia.
The above 2 cases illustrate, the low priority in investigating for galactosemia amongst clinicians. Both infants had history of recurrent gram negative sepsis with failure to thrive, hyperbilirubinemia-which should prompt one to rule out possibility of galactosemia. We are also presenting these 2 cases, as Galactosaemia is much more common than IEMs + also untreated Galactosaemia can lead to mental retardation or even death, which commonly gets interpreted as due to sepsis as in our cases, had we not screened & diagnosed Galactosaemia. Also on the cost factor, it is much cheaper to screen for Galactosemia than to screen for TORCH or Biliary atresia or IEM screen.