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

• Asymptomatic

  […] power of molecular testing to retrospectively diagnose an inherited metabolic disease when biochemical abnormalities have subsided, the value of an accurate and precise diagnosis, and the importance of appropriate genetic counselling in an apparently asymptomatic [ncbi.nlm.nih.gov]

  Newborns are typically asymptomatic, but may present with hyperbilirubinemia or E. coli sepsis. [phpa.health.maryland.gov]

  Galactosemia is an autosomal recessive disorder that affects newborns who are born asymptomatic, apparently well and healthy, then develop serious morbidity and mortality upon consuming milk that contains galactose. [dovepress.com]

  While patients with fully peripheral epimerase deficiency are generally asymptomatic, and patients with marked impairment in multiple tissues can be severely affected, the clinical ramification of partial epimerase deficiency in the non-peripheral tissues [genetics.emory.edu]

• Delayed Growth and Development

  This type can cause cataracts, delayed growth and development, intellectual disability, liver disease, and kidney problems. This sheet will focus on classic galactosemia. Causes Galactosemia is a genetic condition. [winchesterhospital.org]

  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]

• Fatigue

  The most common symptoms include: loss of appetite vomiting jaundice, which is yellowing of the skin and other parts of the body liver enlargement liver damage fluid building up in the abdomen and swelling abnormal bleeding diarrhea irritability fatigue [healthline.com]

  Symptoms include vomiting, diarrhea, lethargy (sluggishness or fatigue ), low blood glucose, jaundice (a yellowing of the skin and eyes), enlarged liver, protein and amino acids in the urine, and susceptibility to infection, especially from gram negative [medical-dictionary.thefreedictionary.com]

• Vomiting

  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]

  The classic form is caused by udpglucose-hexose-1-phosphate uridylyltransferase deficiency, and presents in infancy with failure to thrive; vomiting; and intracranial hypertension. [icd9data.com]

  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]

  To the best of our knowledge, there is no case of galactosemia reported in literature which presented with recurrent neonatal sepsis without hepatomegaly, hyperbilirubinemia, bleeding disorder, vomiting, diarrhea, failure to thrive, hypoglycemia, coagulopathy [ncbi.nlm.nih.gov]

  Bozkowa et al. [6] in a study of 17 galactosemic children described hepatomegaly in 94%, jaundice in 81%, splenomegaly in 79%, vomiting in 62% and diarrhea in 56% cases. [academic.oup.com]

• Diarrhea

  To the best of our knowledge, there is no case of galactosemia reported in literature which presented with recurrent neonatal sepsis without hepatomegaly, hyperbilirubinemia, bleeding disorder, vomiting, diarrhea, failure to thrive, hypoglycemia, coagulopathy [ncbi.nlm.nih.gov]

  Symptoms include vomiting, jaundice, diarrhea, and abnormal growth. The diagnosis is based on blood and urine tests. Even with adequate treatment, affected children still develop mental and physical problems. [merckmanuals.com]

  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]

• Failure to Thrive

  The classic form is caused by udpglucose-hexose-1-phosphate uridylyltransferase deficiency, and presents in infancy with failure to thrive; vomiting; and intracranial hypertension. [icd9data.com]

  […] to thrive, bleeding diathesis, and jaundice, hypoglycemia, hepatocellular damage, and hyperammonemia If untreated in infants can result in Liver damage Sepsis Mental retardation If suspected remove lactose from diet while tests are pending If placed [en.wikibooks.org]

  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]

  Clinical findings seen in newborn period are; poor sucking jaundice, failure to thrive, bleeding diathesis. [medeniyetmedicaljournal.org]

• Lactose Intolerance

  Lactose intolerance occurs when a person is unable to metabolize lactose, but can usually breakdown galactose. Lactose intolerance is rare in infants and more common in older children and adults. [babygooroo.com]

  Milk sugar is called lactose. Lactose is digested by the enzyme lactase, forming the the sugars glucose and galactose. Lactose intolerance is the inability to break down lactose. This causes digestive problems, but is not dangerous to health. [nutritiontactics.com]

  Lactose intolerance occurs when the small intestine does not produce enough lactase enzyme to digest the lactose sugar (9). A person with galactosemia can produce lactase and a person with lactose intolerance will be able to process galactose. [momjunction.com]

  Galactosemia is sometimes confused with lactose intolerance, but galactosemia is a more serious condition. [newworldencyclopedia.org]

  Infants with classic galactosemia cannot be breast-fed due to lactose in human breast milk and are usually fed a soy-based formula.[10] Galactosemia is sometimes confused with lactose intolerance, but galactosemia is a more serious condition. [en.wikipedia.org]

• Nausea

  Compared to Galactokinase Deficiency, symptoms are more severe, and present in infancy with jaundice, hepatomegaly, nausea/vomiting, failure to thrive, infantile cataracts, and intellectual disability. [pixorize.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]

  Affiliated tissues include liver, testes and bone, and related phenotypes are intellectual disability and nausea and vomiting Disease Ontology : 12 A carbohydrate metabolic disorder that involves a defect in galactose metabolism resulting in toxic levels [malacards.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]

• Hypertension

  The classic form is caused by udpglucose-hexose-1-phosphate uridylyltransferase deficiency, and presents in infancy with failure to thrive; vomiting; and intracranial hypertension. [icd9data.com]

  Patients develop cataracts from production of galactitol, which osmotically damages lens fibers; idiopathic intracranial hypertension (pseudotumor cerebri) is rare. Incidence is 1/40,000 births. There are benign and severe phenotypes. [merckmanuals.com]

• Jaundice

  (yellow) R17 ICD-10-CM Diagnosis Code R17 Unspecified jaundice 2016 2017 2018 2019 Billable/Specific Code Type 1 Excludes neonatal jaundice ( P55, P57 - P59 ) newborn P59.9 ICD-10-CM Diagnosis Code P59.9 Neonatal jaundice, unspecified 2016 2017 2018 [icd10data.com]

  Physical exam reveals a temperature of 39 deg Celsius, cataracts, hepatomegaly, and jaundice. The mother says the only change has been that she recently began giving him milk products. [medbullets.com]

  Am 04.08.2016 veröffentlicht In this video the biochemical mechanism for the presence of jaundice in classic galactosemia is explained. [youtube.com]

  In classic galactosemia, symptoms of malnutrition, hepatomegaly, jaundice, and mental deficiency present within the first few weeks of life. The disease is fatal if undiagnosed and untreated. [aao.org]

• Hepatomegaly

  In classic galactosemia, symptoms of malnutrition, hepatomegaly, jaundice, and mental deficiency present within the first few weeks of life. The disease is fatal if undiagnosed and untreated. [aao.org]

  There was no icterus, hepatomegaly and bleeding tendencies. There was no hypotonia and the auditory startle was normal. His weight on admission was 2.8 kg. [academic.oup.com]

  Physical Exam: hepatomegaly, hypotonia, edema, ascites, full fontanelle, encephalopathy, and excessive bruising or bleeding. [pedclerk.bsd.uchicago.edu]

  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]

• Neonatal Jaundice

  (yellow) R17 ICD-10-CM Diagnosis Code R17 Unspecified jaundice 2016 2017 2018 2019 Billable/Specific Code Type 1 Excludes neonatal jaundice ( P55, P57 - P59 ) newborn P59.9 ICD-10-CM Diagnosis Code P59.9 Neonatal jaundice, unspecified 2016 2017 2018 [icd10data.com]

  Galactosaemia should be considered when a term infant gets an E. coli sepsis and when a neonate develops cataracts. It should also be considered with neonatal jaundice and haemorrhage. [patient.info]

  He developed jaundice on his fifth day of life or two days after introduction to breast-feeding. Many possible causes of neonatal jaundice were investigated. [content.sciendo.com]

  Daniel’s story DIAGNOSIS Clinical Diagnosis Most affected infants are detected through newborn screening programs; however, clinicians need to be alert to early signs (poor feeding, prolonged neonatal jaundice) and remove lactose from the diet and initiate [flipper.diff.org]

• Kidney Failure

  Defects in galactose metabolism can cause several severe symptoms, including kidney failure, an enlarged liver, cataracts (clouding of the eye lens), poor growth, and intellectual disability. [web.archive.org]

  This can lead to serious problems such as liver enlargement, kidney failure, brain damage and cataracts. Left untreated, this condition kills as many as 75% of sufferers. [news-medical.net]

  These include an enlarged liver, kidney failure, and brain damage. Why does my child need this test? This test is part of screening done on all newborns. If the newborn screening test is positive, it doesn't mean your child has galactosemia. [urmc.rochester.edu]

  Galactosemia is a condition that can cause complications such as an enlarged liver, kidney failure, cataracts, and brain damage. Diagnosis is usually made shortly after birth as a standard part of newborn screening. [dfps.state.tx.us]

  This accumulation of galactose can cause serious complications such as an enlarged liver, kidney failure, cataracts in the eyes or brain damage. If untreated, as many as 75% of infants with galactosemia will die. [liverfoundation.org]

• Irritability

  […] accumulation of galactose 1-phosphate in liver, kidney, and brain incidence is 1/62,000 births carrier frequency is 1/125 Presentation An infant with classic galactosemia appears normal at birth upon being fed milk, will develop jaundice vomiting lethargy irritability [medbullets.com]

  An infant with galactosemia may develop jaundice, vomiting, lethargy, irritability and convulsions. Causes Galactosemia is an inherited disorder. This means it is passed down through families. [mountsinai.org]

  Symptoms of galactosemia are: Convulsions Irritability Lethargy Poor feeding -- baby refuses to eat formula containing milk Poor weight gain Yellow skin and whites of the eyes (jaundice) Vomiting People with this condition must avoid all milk, products [medlineplus.gov]

  Symptoms of galactosemia are: Convulsions Irritability Lethargy Poor feeding -- baby refuses to eat formula containing milk Poor weight gain Yellow skin and whites of the eyes (jaundice) Vomiting Exams and Tests Tests to check for galactosemia include [ufhealth.org]

  - 발생 빈도 : 1/60,000 정도이다. 2.임상적 증후 - Jaundice(황달), hepatomegaly(간비대증), hepatic cirrhosis(간경변증) - Splenomegaly(비장비대증), ascites(복수) - Feeding difficulties(영양곤란), weight gain(빈약한 체중 증가) - Hypoglycemia(저혈당증), aminoaciduria(아미노산뇨증) - Irritability(자극과민성), [gendix.com]

• 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]

  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]

  […] extreme sleepiness (lethargy) yellowish skin (jaundice) enlarged liver Early treatment helps to prevent serious and life-threatening health problems such as: low blood sugar (hypoglycemia) liver damage cataracts serious complication of infections (sepsis) seizures [newbornscreening.on.ca]

  Additional findings may include poor weight gain, renal failure, coagulopathy, hypoglycemia, seizures, cerebral edema, cataracts, vitreous hemorrhage, neutropenia, and Escherichia coli sepsis. [statpearls.com]

  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]

• Convulsions

  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]

  […] galactose 1-phosphate in liver, kidney, and brain incidence is 1/62,000 births carrier frequency is 1/125 Presentation An infant with classic galactosemia appears normal at birth upon being fed milk, will develop jaundice vomiting lethargy irritability convulsions [medbullets.com]

  An infant with galactosemia may develop jaundice, vomiting, lethargy, irritability and convulsions. Causes Galactosemia is an inherited disorder. This means it is passed down through families. [mountsinai.org]

  Symptoms of galactosemia are: Convulsions Irritability Lethargy Poor feeding -- baby refuses to eat formula containing milk Poor weight gain Yellow skin and whites of the eyes (jaundice) Vomiting People with this condition must avoid all milk, products [medlineplus.gov]

  Symptoms of galactosemia are: Convulsions Irritability Lethargy Poor feeding -- baby refuses to eat formula containing milk Poor weight gain Yellow skin and whites of the eyes (jaundice) Vomiting Exams and Tests Tests to check for galactosemia include [ufhealth.org]

• Speech Disorder

  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]

  Long-term Effects If treatment is done quickly, a baby with galactosemia can live a normal life, although some complications may occur, including: • Cataracts. • Learning disabilities and speech disorders. • Neurological impairment. • Ovarian failure. [breastfeeding-problems.com]

  The specific issues and level of delay varies from child to child, but may include: Learning disabilities Delay in language acquisition Problems with speech are common(majority of children with classic galactosemia have speech disorders) Difficulty with [childrenshospital.org]

  Speech therapy may be necessary for children with childhood apraxia of speech or dysarthria. [rarediseases.org]

• Profound Intellectual Disability

  Early diagnosis and treatment with a lactose-restricted (dairy-free) diet is absolutely essential to avoid profound intellectual disability, liver failure and death in the newborn period. [rarediseases.org]

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.

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

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.

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.

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.

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].

There are no guidelines for prevention of Galactosemia.

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].

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.

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.