Summary

Introduction:

Galactosaemia is an autosomal recessive disease characterised by incapacity to metabolise galactose in glucose. In classical galactosaemia there is a galactose-1-phosphate uridyltransferase (GALT) gene deficiency and  galactose-1-phosphate cannot be converted to glucose 1-phosphate. Consequently, in the case of intake of lactose (which is hydrolysed in the intestine to glucose + galactose), whose main source in the human is milk and dairy products, galactose and galactose 1-phosphate accumulate in blood and tissue. Neonates who present galactosaemia tend to show feeding difficulty and general toxic manifestations during the first weeks of life, including vomiting and diarrhoea, weight loss, jaundice, hepatomegaly and ascites. If lactose is not withdrawn from the diet, the toxic syndrome may progress during the first weeks and give rise to more severe complications. The progressive accumulation of galactitol in the crystalline lens, a metabolite of galactose, can result in the denaturation and precipitation of lenticular protein and formation of cataracts. Accumulation at the level of other organs such as the brain, liver and kidney can lead to poor renal tubular reabsorption, cirrhosis, liver failure or cerebral oedema. Galactosaemia can cause fulminant sepsis due to E. Coli during the first weeks of life. The aim of neonatal galactosaemia screening is a presymptomatic identification and early treatment of galactosaemia, in order to reduce morbidity-mortality and possible disease-related disabilities.

Objectives:

This assessment report was drawn up at the request of the National Health System Interterritorial Council's Services, Insurance & Finance Committee, in response to a proposal from the Galician Regional Health Authority. Its overall objective was to analyse existing evidence on neonatal galactosaemia screening to help decide on its introduction into the National Health System service portfolio. A specific objective was to assess different aspects of the disease, treatment and screening test which might serve to support decision-making. Secondary objectives were to recover information on the different screening strategies used world-wide (diagnostic tests, confirmatory tests, cut points).

Methods:

In order to ascertain if the technology meets the requirements for implementation of national screening in Spain set out in the "Population Screening Framework Document", we carried out two systematic searches of the scientific literature in the leading biomedical databases. The first search was conducted in February 2014, and was targeted at searching for information about internationally implemented screening programmes (detection rate, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV)). The second search was conducted in May 2014, and focused on retrieving all the relevant information about the disease (definition of galactosaemia, clinical characteristics, morbidity-mortality, quality of life, treatment). Papers were selected by two independent reviewers in accordance with a set of pre-defined inclusion/exclusion criteria, and the quality of the scientific evidence was assessed based on the “Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence” scale.

Results, discussion and conclusions: See pdf summary below.