Galactosemia screening: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Galactosemia}} | {{Galactosemia}} | ||
{{CMG}}; {{AE}} {{ | {{CMG}}; {{AE}} {{Sujaya}} | ||
==Overview== | ==Overview== | ||
[[Galactosemia]] satisfies the [[criteria]] for [[newborn]] [[screening]] successfully. Since most babies are born apparently healthy, there is a considerable window for prompt detection of the [[disease]] and appropriate intervention. | |||
==[[Screening]]== | |||
[[Galactosemia]] despite being incurable, qualifies for [[screening]] as early detection can prevent complications. <ref name="pmid30038819">{{cite journal| author=Kotb MA, Mansour L, William Shaker Basanti C, El Garf W, Ali GIZ, Mostafa El Sorogy ST | display-authors=etal| title=Pilot study of classic galactosemia: Neurodevelopmental impact and other complications urge neonatal screening in Egypt. | journal=J Adv Res | year= 2018 | volume= 12 | issue= | pages= 39-45 | pmid=30038819 | doi=10.1016/j.jare.2018.02.001 | pmc=6054589 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30038819 }} </ref> . [[Neonatal]] [[blood]] samples should be collected within 48 hours of birth, reach the laboratory within another 24 hours for the most accurate results. | |||
===Tests used to screen for [[galactosemia]]=== | |||
* '''[[RBC]] [[Galactose]] level''' : Total blood [[galactose]] measurement alone or in combination with [[GALT]] activity in a dried [[blood]] sample is used for primary [[screening]]. [[Galactose-1-phosphate]] more than 10mg% is highly suggestive of [[galactosemia]]. <ref name="pmid25528144">{{cite journal| author=Adam BW, Flores SR, Hou Y, Allen TW, De Jesus VR| title=Galactose-1-phosphate uridyltransferase dried blood spot quality control materials for newborn screening tests. | journal=Clin Biochem | year= 2015 | volume= 48 | issue= 6 | pages= 437-42 | pmid=25528144 | doi=10.1016/j.clinbiochem.2014.12.009 | pmc=4547523 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25528144 }} </ref> | |||
*'''Reducing substances in [[urine]]''': Presence of reducing [[sugars]] in [[urine]] other than [[glucose]] is highly suggestive of [[galactosemia]]. But, this test is highly [[non-specific]] as it is positive in various other clinical conditions ([[prematurity]] <ref name="pmid13479147">{{cite journal| author=HAWORTH JC, MACDONALD MS| title=Reducing sugars in the urine and blood of premature babies. | journal=Arch Dis Child | year= 1957 | volume= 32 | issue= 165 | pages= 417-21 | pmid=13479147 | doi=10.1136/adc.32.165.417 | pmc=2012154 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13479147 }} </ref>, [[proximal renal tubular acidosis]] <ref name="pmid23235953">{{cite journal| author=Haque SK, Ariceta G, Batlle D| title=Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies. | journal=Nephrol Dial Transplant | year= 2012 | volume= 27 | issue= 12 | pages= 4273-87 | pmid=23235953 | doi=10.1093/ndt/gfs493 | pmc=3616759 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23235953 }} </ref> etc.) | |||
* '''[[Galactitol]] excretion in [[urine]]''': Boronic [[acid-based]] methods and multi-well-based [[arrays]] help in detection of [[galactitol]] in [[urine]], a potent [[neurotoxin]]<ref name="pmid27116118">{{cite journal| author=Resendez A, Panescu P, Zuniga R, Banda I, Joseph J, Webb DL | display-authors=etal| title=Multiwell Assay for the Analysis of Sugar Gut Permeability Markers: Discrimination of Sugar Alcohols with a Fluorescent Probe Array Based on Boronic Acid Appended Viologens. | journal=Anal Chem | year= 2016 | volume= 88 | issue= 10 | pages= 5444-52 | pmid=27116118 | doi=10.1021/acs.analchem.6b00880 | pmc=5747966 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27116118 }} </ref>. This test also plays an important role in checking adherence to [[galactose]] restricted [[diet]] and projecting [[cataract]] development in babies born to [[galactosemic]] expectant mothers <ref name="pmid7671961">{{cite journal| author=Jakobs C, Kleijer WJ, Allen J, Holton JB| title=Prenatal diagnosis of galactosemia. | journal=Eur J Pediatr | year= 1995 | volume= 154 | issue= 7 Suppl 2 | pages= S33-6 | pmid=7671961 | doi=10.1007/BF02143800 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7671961 }} </ref>. | |||
* '''[[Hypoglycemia]], [[lactic acidosis]], [[ketonuria]]''': This triad is present in [[neonates]] challenged with [[galactose]], but is seen in a wide [[range]] of [[clinical]] [[conditions]], thus being extremely [[non-specific]]. <ref name="pmid19893643">{{cite journal| author=Christopher R, Sankaran BP| title=An insight into the biochemistry of inborn errors of metabolism for a clinical neurologist. | journal=Ann Indian Acad Neurol | year= 2008 | volume= 11 | issue= 2 | pages= 68-81 | pmid=19893643 | doi=10.4103/0972-2327.41873 | pmc=2771954 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19893643 }} </ref> | |||
* '''[[RBC]] [[Enzyme]] Activity''': [[GALT]] activity assessment, combined with [[galactose-1-phosphate]] in a dried [[blood]] spot, can directly detect disorders associated with [[GALT]] and indirectly those associated with [[GALK]] and [[GALE]] and [[Duarte]] [[galactosemia]]. <ref name="pmid29261178">{{cite journal| author=Pasquali M, Yu C, Coffee B| title=Laboratory diagnosis of galactosemia: a technical standard and guideline of the American College of Medical Genetics and Genomics (ACMG). | journal=Genet Med | year= 2018 | volume= 20 | issue= 1 | pages= 3-11 | pmid=29261178 | doi=10.1038/gim.2017.172 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29261178 }} </ref> | |||
* '''[[Genetic]] testing''': [[DNA]] testing for [[GALT]], [[GALK]] and [[GALE]] [[mutations]] are also available in resourceful [[healthcare]] systems <ref name="pmid29750285">{{cite journal| author=Rajabi F| title=Updates in Newborn Screening. | journal=Pediatr Ann | year= 2018 | volume= 47 | issue= 5 | pages= e187-e190 | pmid=29750285 | doi=10.3928/19382359-20180426-01 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29750285 }} </ref>. | |||
Thus, [[screening]] for [[galactosemia]] is primarily based on estimation of [[galactose]], [[galactose-1-phosphate]] and [[GALT]] in RBCs. Elevated [[galactose]] with absent [[GALT]] activity indicates classic [[galactosemia]], some [[GALT]] activity points towards [[Duarte]] variant, while raised [[sugar]] with normal [[GALT]] suggests deficiency of [[galactokinase]] or [[epimerase]]. | |||
==References== | |||
{{Reflist|2}} | {{Reflist|2}} | ||
{{ | {{WH}} | ||
{{WS}} | |||
[[Category: | [[Category:Needs content]] | ||
[[Category: | [[Category:Endocrinology]] | ||
Latest revision as of 15:05, 18 August 2022
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]
Overview
Galactosemia satisfies the criteria for newborn screening successfully. Since most babies are born apparently healthy, there is a considerable window for prompt detection of the disease and appropriate intervention.
Screening
Galactosemia despite being incurable, qualifies for screening as early detection can prevent complications. [1] . Neonatal blood samples should be collected within 48 hours of birth, reach the laboratory within another 24 hours for the most accurate results.
Tests used to screen for galactosemia
- RBC Galactose level : Total blood galactose measurement alone or in combination with GALT activity in a dried blood sample is used for primary screening. Galactose-1-phosphate more than 10mg% is highly suggestive of galactosemia. [2]
- Reducing substances in urine: Presence of reducing sugars in urine other than glucose is highly suggestive of galactosemia. But, this test is highly non-specific as it is positive in various other clinical conditions (prematurity [3], proximal renal tubular acidosis [4] etc.)
- Galactitol excretion in urine: Boronic acid-based methods and multi-well-based arrays help in detection of galactitol in urine, a potent neurotoxin[5]. This test also plays an important role in checking adherence to galactose restricted diet and projecting cataract development in babies born to galactosemic expectant mothers [6].
- Hypoglycemia, lactic acidosis, ketonuria: This triad is present in neonates challenged with galactose, but is seen in a wide range of clinical conditions, thus being extremely non-specific. [7]
- RBC Enzyme Activity: GALT activity assessment, combined with galactose-1-phosphate in a dried blood spot, can directly detect disorders associated with GALT and indirectly those associated with GALK and GALE and Duarte galactosemia. [8]
- Genetic testing: DNA testing for GALT, GALK and GALE mutations are also available in resourceful healthcare systems [9].
Thus, screening for galactosemia is primarily based on estimation of galactose, galactose-1-phosphate and GALT in RBCs. Elevated galactose with absent GALT activity indicates classic galactosemia, some GALT activity points towards Duarte variant, while raised sugar with normal GALT suggests deficiency of galactokinase or epimerase.
References
- ↑ Kotb MA, Mansour L, William Shaker Basanti C, El Garf W, Ali GIZ, Mostafa El Sorogy ST; et al. (2018). "Pilot study of classic galactosemia: Neurodevelopmental impact and other complications urge neonatal screening in Egypt". J Adv Res. 12: 39–45. doi:10.1016/j.jare.2018.02.001. PMC 6054589. PMID 30038819.
- ↑ Adam BW, Flores SR, Hou Y, Allen TW, De Jesus VR (2015). "Galactose-1-phosphate uridyltransferase dried blood spot quality control materials for newborn screening tests". Clin Biochem. 48 (6): 437–42. doi:10.1016/j.clinbiochem.2014.12.009. PMC 4547523. PMID 25528144.
- ↑ HAWORTH JC, MACDONALD MS (1957). "Reducing sugars in the urine and blood of premature babies". Arch Dis Child. 32 (165): 417–21. doi:10.1136/adc.32.165.417. PMC 2012154. PMID 13479147.
- ↑ Haque SK, Ariceta G, Batlle D (2012). "Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies". Nephrol Dial Transplant. 27 (12): 4273–87. doi:10.1093/ndt/gfs493. PMC 3616759. PMID 23235953.
- ↑ Resendez A, Panescu P, Zuniga R, Banda I, Joseph J, Webb DL; et al. (2016). "Multiwell Assay for the Analysis of Sugar Gut Permeability Markers: Discrimination of Sugar Alcohols with a Fluorescent Probe Array Based on Boronic Acid Appended Viologens". Anal Chem. 88 (10): 5444–52. doi:10.1021/acs.analchem.6b00880. PMC 5747966. PMID 27116118.
- ↑ Jakobs C, Kleijer WJ, Allen J, Holton JB (1995). "Prenatal diagnosis of galactosemia". Eur J Pediatr. 154 (7 Suppl 2): S33–6. doi:10.1007/BF02143800. PMID 7671961.
- ↑ Christopher R, Sankaran BP (2008). "An insight into the biochemistry of inborn errors of metabolism for a clinical neurologist". Ann Indian Acad Neurol. 11 (2): 68–81. doi:10.4103/0972-2327.41873. PMC 2771954. PMID 19893643.
- ↑ Pasquali M, Yu C, Coffee B (2018). "Laboratory diagnosis of galactosemia: a technical standard and guideline of the American College of Medical Genetics and Genomics (ACMG)". Genet Med. 20 (1): 3–11. doi:10.1038/gim.2017.172. PMID 29261178.
- ↑ Rajabi F (2018). "Updates in Newborn Screening". Pediatr Ann. 47 (5): e187–e190. doi:10.3928/19382359-20180426-01. PMID 29750285.