Neonatal Screening For Galactosaemia Research Articles

The Importance of Neonatal Screening for Galactosemia.

Galactosemia is an inborn metabolic disorder caused by a deficient activity in one of the enzymes involved in the metabolism of galactose. The first description of galactosemia in newborns dates from 1908, ever since complex research has been performed on cell and animal models to gain more insights into the molecular and clinical bases of this challenging disease. In galactosemia, the newborn appears to be born in proper health, having a window of opportunity before developing major morbidities that may even be fatal following ingestion of milk that contains galactose. Galactosemia cannot be cured, but its negative consequences on health can be avoided by establishing precocious diagnosis and treatment. All the foods that contain galactose should be eliminated from the diet when there is a suspicion of galactosemia. The neonatal screening for galactosemia can urge early diagnosis and intervention, preventing complications. All galactosemia types may be detected during the screening of newborns for this disorder. The major target is, however, galactose-1-phosphate uridyltransferase (GALT) deficiency galactosemia, which is diagnosed by applying a combination of total galactose and GALT enzyme analysis as well as, in certain programs, mutation screening. Most critically, infants who exhibit symptoms suggestive of galactosemia should undergo in-depth testing for this condition even when the newborn screening shows normal results. The decision to enroll global screening for galactosemia among the specific population still faces many challenges. In this context, the present narrative review provides an updated overview of the incidence, clinical manifestations, diagnosis, therapy, and prognosis of galactosemia, questioning under the dome of these aspects related to the disease the value of its neonatal monitoring.

Pre-linguistic communication skill development in an infant with a diagnosis of galactosaemia

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.

Neonatal Screening for Galactosemia by Quantitative Analysis of Hexose Monophosphates Using Tandem Mass Spectrometry: A Retrospective Study

Classic galactosemia (OMIM 230400) is an inherited disorder in the metabolism of galactose caused by deficiency of the enzyme galactose 1-phosphate uridyl transferase (EC 2.7.7.12). Galactosemia leads to accumulation of galactose and galactose 1-phosphate (gal-1-P) in blood and tissues and, if untreated, produces neonatal death or severe mental retardation, cirrhosis of the liver, and cataracts. Hence, the disorder is included in many neonatal screening programs. We retrospectively analyzed filter-paper blood samples obtained 4-8 days postpartum for routine neonatal screening from 12 galactosemia patients and 2055 random controls. Total hexose monophosphates (HMPs) were used as a marker of gal-1-P and were assayed by negative-ion mode electrospray tandem mass spectrometry (tandem MS) with settings biased toward gal-1-P detection. The predominant precursor/product ion pair m/z 259/79 was used to quantify total HMPs by external standardization. Linear calibration curves were obtained in the range 0-8 mmol/L gal-1-P. The detection limit was 0.1 mmol/L HMP, and total CVs ranged from 13% at the detection limit to <8% at >1 mmol/L HMP. The method was in agreement with an alkaline phosphatase-galactose dehydrogenase method. All samples from galactosemia patients contained increased HMP concentrations (range for patients, 2.6-5.2 mmol/L; range for reference group, <0.10-0.94 mmol/L). The diagnostic sensitivity and specificity were 100% at a cutoff of 1.2 mmol/L HMP. A Duarte/classic galactosemia compound heterozygous sample could be discriminated clearly from both patient and reference samples. Quantitative analysis of HMPs by tandem MS can be used in laboratory investigations of galactosemia.

Clinical features and outcome of eight infants with intrahepatic porto‐venous shunts detected in neonatal screening for galactosaemia

Of 18 newborn infants found to have persistent galactosaemia and without enzyme deficiencies, intrahepatic porto‐venous (P‐V) shunts were the cause in 8 cases. We retrospectively analysed the clinical and biochemical features of the eight infants. Four patients received prednisolone, one of whom with heart failure owing to arteriovenous shunts also underwent hepatic arterial embolization. The other four patients were merely observed without receiving drug therapy. Regardless of treatment, the P‐V shunts disappeared in five infants before the age of 1 y and persisted in three others. All infants showed mild or moderate abnormalities in liver function tests. None exhibited hyperammonemia or neuropsychiatric symptoms related to the shunts. The data indicated that the prognosis of infants with intrahepatic P‐V shunts is generally good. In the absence of complications related to the P‐V shunts, no treatment other than galactose elimination diet is indicated.

Clinical features and outcome of eight infants with intrahepatic porto-venous shunts detected in neonatal screening for galactosaemia.

Of 18 newborn infants found to have persistent galactosaemia and without enzyme deficiencies, intrahepatic porto-venous (P-V) shunts were the cause in 8 cases. We retrospectively analysed the clinical and biochemical features of the eight infants. Four patients received prednisolone, one of whom with heart failure owing to arteriovenous shunts also underwent hepatic arterial embolization. The other four patients were merely observed without receiving drug therapy. Regardless of treatment, the P-V shunts disappeared in five infants before the age of 1 y and persisted in three others. All infants showed mild or moderate abnormalities in liver function tests. None exhibited hyperammonemia or neuropsychiatric symptoms related to the shunts. The data indicated that the prognosis of infants with intrahepatic P-V shunts is generally good. In the absence of complications related to the P-V shunts, no treatment other than galactose elimination diet is indicated.

Interference by antibiotics with neonatal screening for galactosemia

Some centers screen for galactosemia using the metabolite inhibition assay described by Guthrie. L2 In this test, inhibition of bacterial growth caused by galactose (or galactose-1-phosphate) may also be caused by antimicrobial agents contained in the blood sample. In our newborn screening center, all infants born in the 36 hospitals of the northern German cities of Hamburg and Bremen are tested. Every year, of a total of 27,000 infants approximately 20 show positive results in galactosemia screening, but afterward it is found they do not have galactosemia. The purpose of this study was to determine which antimicrobial agents interfere with the galactosemia screening test and at what concentration.