eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia): Differential Diagnoses & Workup

Author: Gerard T Berry, MD, Professor of Pediatrics, Children's Hospital of Boston
Coauthor(s): George A Anadiotis, DO, Consulting Staff, Division of Clinical and Biochemical Genetics, Department of Pediatric Rehabilitation and Development, Emmanuel Children's Hospital
Contributor Information and Disclosures

Updated: Oct 10, 2008

Differential Diagnoses

Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)
Galactokinase Deficiency
Hemochromatosis, Neonatal

Other Problems to Be Considered

Respiratory chain disorders (usually associated with hyperlacticacidemia)
Fanconi-Bickel syndrome
Alpha1-antitrypsin deficiency
Sepsis
Tyrosinemia type 1

Workup

Laboratory Studies

  • All states perform newborn screening.
  • A positive (ie, abnormal) indication on the newborn screen must be followed by a quantitative erythrocyte galactose-1-phosphate uridyltransferase (GALT) analysis by a laboratory that routinely performs biochemical genetic testing and consultation.
  • A GALT isoelectric-focusing electrophoresis test helps distinguish variant forms such as the Duarte defect. GALT genotyping may provide a specific molecular diagnosis. The most common GALT allele in Caucasians is the Q188R mutation. The S135L mutation is common in blacks.22
  • A urine-reducing substances test may help. This test's results are almost always abnormal (ie, positive) in infants with galactosemia who are ingesting lactose. This is a tube test rather than a dipstick test and must be differentiated from the routine urine dipstick test for glucose.

Imaging Studies

  • Patients with galactosemia may exhibit white matter abnormalities on MRI of brain. 
  • Pseudotumor cerebri has been detected in the newborn period.

Other Tests

  • Infants with galactosemia can become jaundiced. Hyperbilirubinemia is often unconjugated but can become conjugated later.
  • Urine examination reveals evidence of albuminuria and, later, a generalized aminoaciduria. Eliminating lactose-containing formula from the diet quickly resolves the albuminuria.

Histologic Findings

  • Fatty infiltration and inflammatory changes initially may occur in the liver.
  • Portal hypertension and pseudoacinar formation occur in later stages.
  • Cirrhosis occurs in the final stage and is indistinguishable from other causes.

More on Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)

Overview: Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)
Differential Diagnoses & Workup: Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)
Treatment & Medication: Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)
Follow-up: Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)
References
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References

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  2. Segal S. Galactosemia unsolved. Eur J Pediatr. 1995;154(7 Suppl 2):S97-102. [Medline].

  3. Fridovich-Keil J, Walter. Galactosemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill Medical Publishing Division; 2008:72.

  4. Mason HH, Turner ME. Chronic galactosemia: report of case with studies on carbohydrates. Am J Dis Child. 1935;50:359-74.

  5. Komrower GM, Lee DH. Long-term follow-up of galactosaemia. Arch Dis Child. Jun 1970;45(241):367-73. [Medline].

  6. Waggoner DD, Buist NR, Donnell GN. Long-term prognosis in galactosaemia: results of a survey of 350 cases. J Inherit Metab Dis. 1990;13(6):802-18. [Medline].

  7. Walter JH, Collins JE, Leonard JV. Recommendations for the management of galactosaemia. UK Galactosaemia Steering Group. Arch Dis Child. Jan 1999;80(1):93-6. [Medline].

  8. Garden AS, Davidson DC. Recommendations for the management of galactosaemia. Arch Dis Child. Mar 2000;82(3):266. [Medline].

  9. Antshel KM, Epstein IO, Waisbren SE. Cognitive strengths and weaknesses in children and adolescents homozygous for the galactosemia Q188R mutation: a descriptive study. Neuropsychology. Oct 2004;18(4):658-64. [Medline].

  10. Levy HL, Brown AE, Williams SE, de Juan E Jr. Vitreous hemorrhage as an ophthalmic complication of galactosemia. J Pediatr. Dec 1996;129(6):922-5. [Medline].

  11. Waisbren SE, Norman TR, Schnell RR, Levy HL. Speech and language deficits in early-treated children with galactosemia. J Pediatr. Jan 1983;102(1):75-7. [Medline].

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  14. Kaufman FR, Kogut MD, Donnell GN, Goebelsmann U, March C, Koch R. Hypergonadotropic hypogonadism in female patients with galactosemia. N Engl J Med. Apr 23 1981;304(17):994-8. [Medline].

  15. Guerrero NV, Singh RH, Manatunga A, Berry GT, Steiner RD, Elsas LJ 2nd. Risk factors for premature ovarian failure in females with galactosemia. J Pediatr. Dec 2000;137(6):833-41. [Medline].

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  22. Elsas LJ 2nd, Langley S, Paulk EM, et al. A molecular approach to galactosemia. Eur J Pediatr. 1995;154(7 Suppl 2):S21-7. [Medline].

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Further Reading

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Keywords

galactose-1-phosphate uridyltransferase deficiency, GALT, hypergalactosemia, classic galactosemia, GALT deficiency, Escherichia coli, E coli, sepsis, Duarte variant, liver dysfunction, hepatomegaly, cataract, hypotonia, ascites, learning disorder, delayed language acquisition, language deficit, speech deficit, hypergonadotropic hypogonadism, primary ovarian insufficiency

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Contributor Information and Disclosures

Author

Gerard T Berry, MD, Professor of Pediatrics, Children's Hospital of Boston
Gerard T Berry, MD is a member of the following medical societies: American College of Medical Genetics, American Diabetes Association, American Society of Human Genetics, Federation of American Societies for Experimental Biology, Lawson-Wilkins Pediatric Endocrine Society, Sigma Xi, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

George A Anadiotis, DO, Consulting Staff, Division of Clinical and Biochemical Genetics, Department of Pediatric Rehabilitation and Development, Emmanuel Children's Hospital
George A Anadiotis, DO is a member of the following medical societies: American Medical Association and American Society of Human Genetics
Disclosure: Nothing to disclose.

Medical Editor

Robert D Steiner, MD, Professor, Departments of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Oregon Health & Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital and Doernbecher Children's Hospital; Deputy Director, Oregon Clinical and Translational Research Institute
Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research
Disclosure: Genzyme Honoraria Speaking and teaching; Genzyme Grant/research funds Other; Shire Honoraria Speaking and teaching; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Speaking and teaching; Biomarin Consulting fee Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Hagop Youssoufian, MD, MSc, Vice President of Clinical Research, ImClone Systems Incorporated
Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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