Galactosemia
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The A to G mutation in the p.Q188R variant introduces a site of cleavage by the restriction endonuclease HpaII, which permits family studies and population screening. In addition to Q188R, p.K285N is also common in Caucasians; these two were found in more than 70 percent of alleles [13]. A 4-bp deletion in the 5’ region of the GALT gene has been found to be linked to the Duarte allele and to yield reduced activity of the enzyme [66]. The DAT+314 as opposed to N is common in nonhuman species, such as chimpanzee, macaque, and mouse, suggesting that it is the ancestral gene [66]. An interesting biochemical phenotype was found in a family in which the proband had classical galactosemia [67]. He had inherited two mutations in cis from his father, p.N324D and E204K. From the mother, he received a mutation in the splice-site acceptor of intron C. Enzyme activity in the father was nearly normal. An asymptomatic sister had compound heterozygosity for three mutations, p.E293K–N324D/N324D. Her erythrocyte enzyme activity was normal. It was speculated that the codons for E203K and N314D led to intra-allelic complementation in cis, but in fact the result is in keeping with what was later established for the effect of the p.N314D Duarte mutation. The ideal approach to diagnosis of galactosemia is through routine neonatal screening. A protocol for the screening and management of galactosemia is given in Table 57.2. The assay in the United States is for the activity of galactose-1-phosphate uridyltransferase in dried blood on filter paper. In some countries, the assay is for galactose, and this will also detect galactokinase deficiency. The test for galactose will also be positive in patients with congenital shunts from portal to systemic vessels [68]. A positive screening test is confirmed by quantification of activity in freshly obtained erythrocytes in the fluorimetric assay for NADPH formed along with glucose-6-phosphate from the glucose-1-phosphate product. In classic galactosemia, the activity approximates zero. Variants with greater activity than this can be elucidated by electrophoresis or by mutational analysis. It is important for clinicians to recognize the early clinical manifestation of galactosemia and its infectious complications, because some developed countries have given up neonatal screening for this disease, and even in screened infants, classical disease can develop before the results of screening are known. The screening assay is followed by quantification of activity in freshly obtained erythrocytes. In California, testing for common mutations is carried out on the initial blood spots.
Metabolic Disorders II
John F. Pohl, Christopher Jolley, Daniel Gelfond in Pediatric Gastroenterology, 2014
Galactosemia is a disorder of galactose metabolism that can result in life-threatening complications including feeding problems, failure to thrive, hepatocellular damage, bleeding, and sepsis in untreated infants. Galactose metabolism is important for energy production, glycogen stores, and galactosylation of glycolipids and glycoproteins. This chapter will focus on classic galactosemia (OMIM 230400), a potentially lethal inherited disorder caused by the deficiency of galactose-1-phosphate-uridyltransferase (GALT). Despite adequate treatment with a lactose/galactose restricted diet, children with galactosemia remain at increased risk for developmental delays, speech problems, and abnormalities of motor function. Galactosemia affects about 1 in every 30,000–60,000 babies.
Contraindications to breastfeeding
Amy Brown, Wendy Jones in A Guide to Supporting Breastfeeding for the Medical Profession, 2019
Galactosaemia occurs in about 1 in 45,000 births (Walter et al. 1999). It is a deficiency of enzyme galactose-1-phosphate uridyl transferase transmitted as an autosomal-recessive trait. The liver enzyme that converts galactose to glucose is absent, so the baby is unable to metabolise lactose. The infants appear normal at birth but often have feeding difficulties, with jaundice, enlarged liver, lethargy, irritability, vomiting and poor weight gain (Walker 2006). Without treatment mental retardation develops. Galactosaemia is one of the few instances where breastfeeding needs to stop immediately to be replaced by galactose-free formula milk. Approximately one in every 19,000 infants born in Ireland may have this condition. However, it is particularly common among infants born to Traveller parents, in whom the incidence is approximately 1 in 450 births. Babies of the Traveller community are offered the Beutler test on day 1 of life and are fed galactose-free feed (soya-based) formula and not breastfed until the result of the test is available. This protects the infant if he/she has the condition (UCD School of Public Health and Population 2010).
Repurposing drugs for the treatment of galactosemia
Published in Expert Opinion on Orphan Drugs, 2019
Introduction: Galactosemia results from mutations in genes which code for enzymes involved in the metabolism of galactose. It has a wide range of symptoms ranging from the relatively mild (early onset cataracts) to severe damage to the liver, brain and ovaries. The only treatment is the removal or reduction of galactose in the diet. This treatment is unsatisfactory, particularly in the most severe forms of the disease. Considerable efforts are being made to develop specific therapies for galactosemia. These include gene therapies, pharmacological chaperones, drugs to block the production of potentially toxic metabolites and enzyme replacement therapy. Areas covered: This review considers existing drugs, nutrients and treatments which could be relatively rapidly repurposed for the treatment of galactosemia. If successful, these would improve the prognosis for galactosemia patients. Expert opinion: Dietary antioxidants which are widely used and generally considered safe (e.g. resveratrol, purple sweet potato color) should be tested for their efficacy in galactosemia. Pharmaceutical antioxidants (e.g. idebenone) should be considered. Phosphate supplementation, along with careful monitoring of phosphate levels in the patient’s diet should also be considered. Efforts to develop specific therapies for galactosemia should continue.
Pre-linguistic communication skill development in an infant with a diagnosis of galactosaemia
Published in Developmental Neurorehabilitation, 2014
Fiona M. Lewis, David J. Coman, Sarah Kilcoyne, Bruce E. Murdoch, Maryanne Syrmis
Background: Neonatal screening for galactosaemia (GAL) identifies the condition early, but subsequent biomedical and genetic testing fails to identify which subgroup of infants with GAL are at most risk of the language disorders associated with the condition. This study aims to present preliminary data on an infant with GAL based on assessment of pre-linguistic communication behaviours known to underpin language development. Methods: This single case-control study profiles the pre-linguistic skills of a 13-month-old infant with GAL. The Index Infant's performance was descriptively compared to that of a typically developing, suitably matched control infant. Results: The Index Infant was identified as presenting with clinically significant delays on 9 of the 11 pre-linguistic skills assessed. Discussion and Conclusion: The early identification of risk of developmental language difficulties in the Index Infant allows for the implementation of early intervention using the infant's parents as facilitators of language stimulation. Monitoring of the infant's progress is warranted.
Learning disabilities and language pathology in patients with galactosemia
Published in Logopedics Phoniatrics Vocology, 1996
Randi Korsvig Rasmussen, Anne Berit Andreassen, Petter Strømme, Thor Willy Ruud Hansen
In spite of adequate dietary regimen, many patients with galactosemia have developmental abnormalities. We studied 8 patients with galactosemia, aged 9 months to 19 years who had all been treated with a galactose-free diet from an early stage. Neurological functioning, general developmental, and language and speech development were assessed in all cases. The results show that even medically well treated children and young adults with galactosemia are at risk to develop disabilities, including mental retardation, speech and language disabilities. Verbal dyspraxia was diagnosed in 3 of 6 patients, who had acquired verbal language, all with IQ 70 or below. This may indicate that verbal dyspraxia is just one symptom among others in patients with galactosemia and mental retardation.
Related Knowledge Centers
- Hexose
- Vomiting
- Intracranial Hypertension
- Galactokinase
- Phosphate Uridylyltransferase
- Failure to Thrive
- Metabolic Inborn Brain Diseases