Edit concept Create issue ticket

Galactosemia

Galactose Intolerance

Galactosemia is a rare genetic metabolic disorder, characterized by the deficiency of an enzyme necessary for galactose metabolism and characterized by elevated levels of galactose in the blood.


Presentation

In untreated infants with severe cases of deficient GALT activity, the following findings are typically present: Sepsis (E. coli), hypotonia, lethargy, cataracts, liver dysfunction, bleeding from coagulopathy, jaundice, poor growth within the first few weeks of life etc [8].

In some cases, ascites is spotted during early infancy. In rare occasions, it is diagnosed within the first few days of life. For infants or children with cataracts, galactosemia must be excluded. This is important and seeing an ophthalmologist is advised because some cataracts are not visible except through the use of a slitlamp. This is especially the case with congenital cataracts.

Although its prevalence is unknown, vitreous hemorrhage is a common complication of galactosemia. There is an enigmatic linkage of E. coli sepsis and galactosemia. Galactosemia is often high on the differential diagnosis of term infants with sepsis brought about by infection with this pathogen. Speech, language and learning problems are very common and so language acquisition might be delayed.

In adults with this condition, the most common findings include primary ovarian insufficiency in women or hypergonadotropic hypogonadism. Most black women who have variants of the disease can still get pregnant however. Neurologic abnormalities like tremor, ataxia, dystonia equally occur in most of the patients. Short stature is another minor abnormality. There have been reports of severe galactosemia in patients who went off diet therapy since childhood. This has raised concerns regarding

Delayed Growth and Development
  • The signs and symptoms of galactosemia type III vary from mild to severe and can include cataracts, delayed growth and development, intellectual disability, liver disease, and kidney problems.[ghr.nlm.nih.gov]
Vomiting
  • The presenting symptoms which include vomiting, diarrhea, jaundice, and failure to thrive result from the ingestion of foods containing galactose--breast milk and formulas containing cow's milk.[ncbi.nlm.nih.gov]
  • Snapshot A two-week-old infant is brought to the emergency department because of diarrhea, poor feeding, abdominal distention, and vomiting for the past 3 days.[medbullets.com]
  • Vomiting, liver enlargement, and jaundice are often the earliest signs of the disease, but bacterial infections (often severe), irritability, failure to gain weight, and diarrhea may also occur.[liver.ca]
  • Any baby with symptoms of galactosemia (for example, vomiting) should be given enzyme tests. Treatment Galactosemia I and II are treated by removing galactose from the diet.[medical-dictionary.thefreedictionary.com]
  • A build-up of galactose may initially cause symptoms in infants including feeding difficulties, lack of energy, weight loss, nausea and vomiting.[geneticdiseasefoundation.org]
Diarrhea
  • The presenting symptoms which include vomiting, diarrhea, jaundice, and failure to thrive result from the ingestion of foods containing galactose--breast milk and formulas containing cow's milk.[ncbi.nlm.nih.gov]
  • Report of Case A white male infant aged 4½ mo. was admitted to the hospital with the complaints of poor gain of weight, retarded development, pallor, vomiting and diarrhea since birth. He was the fifth child of apparently healthy parents.[pediatrics.aappublications.org]
  • Symptoms appear in the neonatal period after ingestion of galactose and include vomiting, diarrhea, failure to thrive, lethargy, hypotonia, jaundice, hepatomegaly, septicemia, cataracts and bleeding tendencies.[genedx.com]
  • Background Information for Galactosemia (GALT) Enzyme Activity and 9 Mutations: Characteristics: Affected infants present at 3-14 days old with poor feeding, vomiting, diarrhea, jaundice, lethargy progressing to coma, and abdominal distension with hepatomegaly[ltd.aruplab.com]
  • Clinical features Most babies born with galactosemia do not present with symptoms initially but jaundice, diarrhea and vomiting soon develop. The baby fails to thrive and may lose weight.[news-medical.net]
Lactose Intolerance
  • Lactose intolerance is rare in infants and more common in older children and adults. Symptoms of lactose intolerance include bloating, cramping, and diarrhea.[babygooroo.com]
  • Galactosemia is sometimes confused with lactose intolerance, but galactosemia is a more serious condition.[newworldencyclopedia.org]
  • Galactosemia should not be confused with lactose intolerance, which is an allergic reaction some children get from dairy products.[dfps.state.tx.us]
  • Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.[naturallivingcenter.net]
Nausea
  • A build-up of galactose may initially cause symptoms in infants including feeding difficulties, lack of energy, weight loss, nausea and vomiting.[geneticdiseasefoundation.org]
  • Shortly after birth an intolerance to milk occurs; it is evidenced by anorexia, nausea, vomiting, and diarrhea and causes failure to thrive. Hepatosplenomegaly, cataracts, and mental retardation develop.[medical-dictionary.thefreedictionary.com]
  • These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl ) or disulfiram (Antabuse ). Avoid if pregnant or breastfeeding.[naturallivingcenter.net]
Jaundice
  • We report a 51-day-old infant with congenital intrahepatic porto-systemic venous shunt associated with galactosemia, who presented with cholestatic jaundice. He was treated with ursodeoxycholic acid, calcium supplements and galactose-free diet.[ncbi.nlm.nih.gov]
  • Galactosemia in newborns and infants is associated with the following symptoms: jaundice, hepatomegaly, failure to thrive, feeding difficulties, hypoglycemia, convulsions, lethargy, amino-aciduria, cataracts, hepatic cirrhosis, ascites, and mental retardation[ncbi.nlm.nih.gov]
  • We are reporting such a rarest form of galactosemia presenting with progressively increasing cholestatic jaundice and failure to thrive at one month of age.[ncbi.nlm.nih.gov]
  • The presented case was a 2-month-old, Thai female infant with persistent cholestatic jaundice, bilateral posterior subcapsular cataracts, and hepatomegaly.[ncbi.nlm.nih.gov]
  • The presenting symptoms which include vomiting, diarrhea, jaundice, and failure to thrive result from the ingestion of foods containing galactose--breast milk and formulas containing cow's milk.[ncbi.nlm.nih.gov]
Hepatomegaly
  • Galactosemia in newborns and infants is associated with the following symptoms: jaundice, hepatomegaly, failure to thrive, feeding difficulties, hypoglycemia, convulsions, lethargy, amino-aciduria, cataracts, hepatic cirrhosis, ascites, and mental retardation[ncbi.nlm.nih.gov]
  • The presented case was a 2-month-old, Thai female infant with persistent cholestatic jaundice, bilateral posterior subcapsular cataracts, and hepatomegaly.[ncbi.nlm.nih.gov]
  • .- hepatomegaly (an enlarged liver), cirrhosis, renal failure, cataracts, vomiting, seizure, hypoglycemia, lethargy, brain damage, and ovarian failure. Without treatment, mortality in infants with galactosemia is about 75%.[nicklauschildrens.org]
  • […] seems reasonable to suppose that many others have not been reported and still others have gone unrecognized.The characteristic clinical manifestations of this congenital metabolic defect are early nutritional failure, physical and mental retardation, hepatomegaly[nejm.org]
  • Symptoms appear in the neonatal period after ingestion of galactose and include vomiting, diarrhea, failure to thrive, lethargy, hypotonia, jaundice, hepatomegaly, septicemia, cataracts and bleeding tendencies.[genedx.com]
Retinal Hemorrhage
  • Thus we believe that retinal hemorrhage is the most likely source of the vitreous hemorrhage and that the coagulopathy associated with neonatal disease in galactosemia leads to vitreous hemorrhage.[ncbi.nlm.nih.gov]
Seizure
  • It manifests in the central nervous system in the form of hypotonia, seizures, mental retardation, tremor, ataxia, and progressive cerebellar as well as extrapyramidal features.[ncbi.nlm.nih.gov]
  • If left untreated, more serious complications may include seizures, liver damage and potential for delayed development. GALT can be fairly well managed with a lactose-free diet throughout life.[geneticdiseasefoundation.org]
  • .- hepatomegaly (an enlarged liver), cirrhosis, renal failure, cataracts, vomiting, seizure, hypoglycemia, lethargy, brain damage, and ovarian failure. Without treatment, mortality in infants with galactosemia is about 75%.[nicklauschildrens.org]
  • Screen for decreased RBC concentrations of galactose 1-phosphate uridyltransferase increased concentrations of galactose 1-phosphate (in serum and urine) Differential hereditary fructose intolerance presents with vomiting, lethargy, and seizures when[medbullets.com]
  • Common symptoms include jaundice, feeding difficulties, vomiting, poor weight gain, irritability, lethargy, seizures, cataracts, and mental retardation. The liver and spleen are usually enlarged.[drgreene.com]
Pyramidal Tract Signs
  • With treatment, the edema gradually resolved, although it persisted longer within the white matter and was associated with transient bilateral pyramidal tract signs.[ncbi.nlm.nih.gov]
Vocal Tremor
  • Three children, two diagnosed with CAS and one not diagnosed with a motor speech disorder, had vocal tremors. Treatment of voice dysfunction in neurogenic speech disorders is discussed.[ncbi.nlm.nih.gov]

Workup

In many cases, workup begins with newborn screening. With a positive indication for the newborn screening quantitative erythrocyte galactose-1-phosphate uridyltransferase (GALT) analysis follows. The test has to be carried out in laboratories that perform biochemical genetic consultation and testing.

To help distinguish variant forms like the Duarte defect a GALT isoelectric-focusing electrophoresis test is conducted. GALT genotyping provides a specific molecular diagnosis in some cases. In Caucasians, the most common GALT allele is the Q188R mutation. In blacks, it is the S135L mutation [9].

Urine reducing substance tests will also help in establishing this defect. The results of the tests are often abnormal, in children with this problem taking in lactose diets. Rather than a dipstick test, this test is a tube test and it has to be differentiated from the normal urine dipstick test for glucose. Imaging scans like an MRI can also be used to confirm brain abnormalities.

Treatment

The only treatment for galactosemia is eliminating lactose and galactose from the diet.

Prognosis

When left untreated, classic cases of galactosemia can be life threatening. Fortunately, medical advancements around developed countries of these world means that infants are treated before the condition gets out of hand.

If the infant with galactosemia is severely ill before treatment (with liver dysfunction, coagulopathy, sepsis) he or she may develop permanent liver, eye or brain damage. Cataracts are generally totally reversible. Patients with severe galactosemia who do not receive treatment rarely survive past the newborn period [10].

Again, even when the right dietary therapy is there, majority of patients show at least 1-2 complications over the long term.

Etiology

Classic galactosemia cases are caused by a severe deficiency in GALT [6]. This deficiency is a genetic condition of the autosomal recessive kind. The gene for GALT can be found on chromosome 9p13.

Epidemiology

In the United States, the incidence of this disorder is 1 case per 40,000-60,000 individuals. Internationally, there is a wide variation in terms of incidence. For instance, this ailment is prevalent in 1 case out of 70,000 people in the UK but in Ireland, only 1 out of 20,000 people. The disorder is not commonly reported amongst Asians [3].

Life expectancy has not been properly documented in individuals with this defect. However, there is a high mortality rate amongst new born infants who often develop sepsis caused by Escherichia coli. With the institution of a galactose-restricted diet, most patients reach adulthood [4].

Galactosemia can be seen in all races but the variants are dependent on the type of gene defect. The variants are mostly seen amongst the black population. Amongst affected individuals, 10% of enzyme activity is reported in the liver but there is no activity in the erythrocytes. In places where newborn screening is not possible, the individual’s ability to tolerate the ingestion of some milk hinders diagnosis.

The Duarte variant is a recognized benign variety of the galactosemia problem. Amongst neonates with this defect, the newborn screening test results may or may not be positive and some of the neonates can easily tolerate normal diets. Such individuals may show increased galactose metabolite levels during infancy but less so in childhood [5].

It is still unknown whether dietary galactose restriction is necessary or beneficial for patients with the Duarte variant of galactosemia. A conservative approach which involves galactose restriction in the first year of life is taken by most metabolic disease experts. However, the restriction is largely down to the theoretical concerns of galactose toxicity in children with this Duarte variant.

Galactosemia affects both males and females equally. The disease is often diagnosed at infancy the most but variant forms of galactosemia can be diagnosed much later in adult life.

Sex distribution
Age distribution

Pathophysiology

Hypergalactosemia is associated mostly with 3 major enzyme deficiencies. They are as follows:

  • Galactokinase’s conversion of galactose to galactose-1-phosphate (not a common deficiency).
  • Uridine diphosphate (UDP) galactose-4-epimerase’s epimerization of UDP galactose to UDP glucose (not also common).
  • GALT responsible for hereditary galactosemia. This is the most common deficiency. This enzyme catalyzes the conversion of galactose-1-phospahte and UDP glucose into UDP galactose and glucose-1-phosphate. People with GALT deficiency show abnormal galactose tolerance [7].

Prevention

There are no guidelines for prevention of Galactosemia.

Summary

Galactosemia in its hereditary form is a common carbohydrate metabolism condition. The disorder may be life threatening during the new born period.

First described in the variant patient in 1935 by mason and turner, GALT deficiency is the most common cause of hypergalactosemia. GALT means galactose-1-phosphate uridyltransferase [1].

The toxicity associated with infantile diseases can be dealt with appropriately by removing lactose However, complications occur long term [2].

Patient Information

For children who have the Galactosemia defect, a good deal of collaboration is required between the parents and the health personnel. Such children must only be given meals as prescribed by the experts.

However, you need to keep in mind that there is basically no classic diet for this defect. With different parents, doctors and clinics, different rules are followed. We have mentioned two guides followed by many nutritionist, clinics and doctors. You can get them from any closest health office to you.

It is still advised that you check with your clinic before settling for a specific diet regime. The importance of following your own doctor’s advice is important because various clinics have different recommendations.

This may add to the frustration of dealing with the condition but with proper collaboration between parents and the clinic, it becomes easier to make the best decision for the condition.

References

Article

  1. Berry GT, Segal S and Gitzelmann R. Disorders of Galactose Metabolism. In: Fernandes J, Saudubray M, van den Berghe G, Walter JH. Inborn Metabolic Diseases - Diagnosis and Treatment. 4. New York, NY: Springer-Verlag, Inc; 2006.
  2. Segal S. Galactosemia unsolved. Eur J Pediatr. 1995;154(7 Suppl 2):S97-102.
  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.
  6. Hirokawa H, Okano Y, Asada M, et al. Molecular basis for phenotypic heterogeneity in galactosaemia: prediction of clinical phenotype from genotype in Japanese patients. Eur J Hum Genet 1999; 7:757.
  7. National Newborn Screening and Genetics Resource Center; 2002 Newborn Screening and Genetic Testing Symposium.
  8. Coman DJ, Murray DW, Byrne JC, et al. Galactosemia, a single gene disorder with epigenetic consequences. Pediatr Res 2010; 67:286.
  9. Beutler E, Baluda MC, Sturgeon P, Day R. A new genetic abnormality resulting in galactose-1-phosphate uridyltransferase deficiency. Lancet 1965; 1:353.
  10. Kelley RI, Segal S. Evaluation of reduced activity galactose-1-phosphate uridyl transferase by combined radioisotopic assay and high-resolution isoelectric focusing. J Lab Clin Med 1989; 114:152.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2017-08-09 17:19