Uzma Saleem, Mahmood S., Kamran S.H, Mutt M.A, Ahmad B
1 College of Pharmacy, G.C.University, Faisalabad, Pakistan. 2 Lahore General Hospital, Lahore, Pakistan. 3 University College of Pharmacy, University of the Punjab, Lahore, Pakistan.
Keywords: Galactosemia, carbohydrate metabolic disorder, GALT

Galactosemia is an autosomal carbohydrate metabolic disorder caused by the deficiency of galactose 1-phosphate uridyltransferase (GALT). Frequency of occurrence of this disorder varies, more common in Irish population and very less in Asians. There are three types of galactosemia but GALT is most common. The prominent sign and symptoms include hypoglycemia, hepatomegaly, ascities, jaundice, poor feeding and vomiting. Cataracts, premature ovarian failure, decreases in bone mineral density, mental retardation are few of the long term complications. Symptoms appear within first few days of galactosemic infants. Strict dietary control (i.e. galactose free diet) can prevent acute toxicity but it does not guarantee the prevention of long term complications. The only treatment is complete elimination of galactose/lactose free diet and calcium supplements are used as supportive therapy.

Article Information

Identifiers and Pagination:
First Page:38
Last Page:44
Publisher Id:JAppPharm (2012 ). 4. 38-44
Article History:
Received:October 18, 2011
Accepted:December 7, 2011
Collection year:2011
First Published:January 10, 2012

Galactosemia is an inborn carbohydrate metabolic disorder and can be fatal and life-threatening during the newborn period [1, 2, 3]. Galactosemia is a rare genetic and an autosomal recessive disorder (meaning a child must inherit one defective gene from each parent to show the disease), caused by the deficiency of galactose 1-phosphate uridyltransferase (GALT) [4, 5, 6].

Galactosemia was first described in Germany by von Reuss as cited by George  in 1908 and by Göppert in 1917, and first in the United States by Mason and Turner in 1935 [7, 8, 9]. Kalckar et al. identified in 1956 that galactosemia is due to defect in galactose metabolism [5].

The synonymous of galactosemia are galactose diabetes, essential galactosuria, congenital galactosemia, congenital galactosuria, galactosis, and galactemia [7].

Incidence Rate

The incidence rate varies in different populations i.e. 1 case per 40,000-60,000 persons (unites states) 3, 1 case in 70,000 people (UK) but 1 case in 20,000 people in Ireland. Galactosemia is very common within the Irish Traveller population. In Asians, this disorder is less common [10].

Types of Galactosemia

There are three types

  1. Type 1, Classic Galactosemia, the most common and most severe form. This is due to Galactose-1 phosphate uridyl transferase (GALT) deficiency.
  2. Type 2, Deficiency of galactose kinase (GALK/GALK1)
  3. Type 3, Deficiency of galactose-6-phosphate epimerase (GALE) [3, 11]

Clinical Signs & Symptoms

Aminoaciduria ,Hepatomegaly, Ascites ,Hypoglycemia are prominent signs of this disorder.. Symptoms include Convulsions, Irritability, Lethargy, Poor feeding, Poor weight gain, jaundice, Vomiting. Septicemia (blood infection with E. coli) may be responsible for these symptoms. Galactosemic infants whom galactose containing diet was not stopped e.g. breast milk, can develop symptoms within the first few days of life [1, 3].



They include premature ovarian failure and neuropsychiatric features, including cognitive problems, learning difficulties, behavioral changes, such as withdrawn personality, and speech difficulties, Cataracts, liver cirrhosis, Mental retardation, septicemia with E. coli, Tremors and uncontrollable motor functions, ataxia, decrease in bone mineral density [1, 12, 13, 14, 15].

Normal Galactose Metabolism]


Toxic Metabolites of Galactose

Galactitol and Galactose-1-phosphate are two toxic galactose metabolites. Galactitol is responsible for the cataracts, and Galactose-1-phosphate induces the rest of the clinical symptoms. To distinguish galactosemic patients from normal subjects urine and plasma levels of Galactitol should be measured. Early diagnosis and strict use of milk free products can help the patient to live a relatively normal life. However, mild intellectual impairment may develop, even in people who avoid galactose [1, 17].

What genes are related to galactosemia?

Mutations in the GALE, GALK1, and GALT genes cause galactosemia.

Type of Galactosemia

Gene Mutation

Classic Galactosemia, type I

GALT gene

Galactosemia type II

GALK1 gene

Galactosemia type III

GALE gene

These genes provide all the necessary instructions required for making enzymes that are essential for galactose metabolism. Galactose is broken down into glucose, another simple sugar and other molecules in the presence of these enzymes and body can store easily these break down products or use them for energy. There are two types of mutations in GALT gene: In one type there is complete elimination of activity of enzyme produced by GALT, this is called classic Galactosemia and in 2nd type of GALT gene mutation, there is reduction in activity of enzyme rather than complete elimination and this is called Duarte Galactosemia variant. The Duarte Galactosemia variant is caused by N314D. Homozygosity for N314D reduces GALT activity to 50%. People with the Duarte variant tend to have much milder features of Galactosemia [4, 18, 19, 20].

Exact Location of Galt Gene


The GALT gene is located on the short (p) arm of chromosome 9 at position 13 (9p13).

More precisely, the GALT gene is located from base pair 34,646,634 to base pair 34,650,573 on chromosome 9 [6, 19, 21, 22, 23].


Following Laboratory tests help in diagnosis of this autosomal disorder:

1. Prenatal diagnosis by directly measuring the enzyme galactose-1-phosphate uridyl transferase [1].

2. A Galt isoelectric-focusing electrophoresis test for specific molecular diagnosis. The most common Galt allele in caucasians is the Q188r mutation. The S135l mutation is common in blacks [23].

3. Blood culture for bacterial infection (E. COLI sepsis) [1].

4. Measurement of galactose-1-phosphate uridyl transferase activity in RBC [1, 24].

5. Detection of reducing substances in urine by using tube test 1, 24.

6. Detection of ketones in the urine [1].

7. Multiplex enzyme assay for galactosemia in erythrocytes using ultra-performance liquid chromatography-tandem mass spectrometry [25].

Brain Imaging of Galactosemic Patients

Brain MR Imaging and proton MR spectroscopy studies showed cerebral and cerebellar atrophy, multiple small hyper intense lesions in the cerebral white matter on T2-weighted images [1, 26, 27, 28, 29, 30].


a) Complete elimination of dietary lactose/galactose, use Soy formula, Meat-based formula or Nutramigen (a protein hydrolysate formula), anyother lactose-free formula   b) supportive therapy with calcium supplements   c) use antibiotic also in case of septicemic patient

This treatment can reverse growth failure, Hepatomegaly, formation of cataract and also reduce the death reports due to septicemia but long term complications can not be prevented [1].

Medical Care

Acute toxicity symptoms of this inborn disorder can be prevented in infants by immediate dietary galactose restriction (do not give mother feed) but it does not ensure absence of all symptoms and long-term complications routinely occur [4, 33, 34]. Long term complications of Galactosemia are independent of diet [35].


Galactosemia is a rare genetic autosomal recessive disorder. It is linked with mutations in GALT, GALE, GALK1 genes. When galactosemic infants feed breast milk, symptoms start appearing soon after birth. Galactose/ Lactose free diet is pre-requisite condition for galactosemic persons to pass normal life, though long term complications can not be prevented because they are independent of diet.



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Welcome to the research group of Prof. Dr. Cornelia M. Keck in Marburg. Cornelia M. Keck is a pharmacist and obtained her PhD in 2006 from the Freie Universität (FU) in Berlin. In 2009 she was appointed as Adjunct Professor for Pharmaceutical and Nutritional Nanotechnology at the University Putra Malaysia (UPM) and in 2011 she obtained her Venia legendi (Habilitation) at the Freie Universität Berlin and was appointed as a Professor for Pharmacology and Pharmaceutics at the University of Applied Sciences Kaiserslautern. Since 2016 she is Professor of Pharmaceutics and Biopharmaceutics at the Philipps-Universität Marburg. Her field of research is the development and characterization of innovative nanocarriers for improved delivery of poorly soluble actives for healthcare and cosmetics. Prof. Keck is executive board member of the German Association of Nanotechnology (Deutscher Verband Nanotechnologie), Vize-chairman of the unit „Dermocosmetics“ at the German Society of Dermopharmacy, active member in many pharmaceutical societies and member of the BfR Committee for Cosmetics at the Federal Institute for Risk Assessment (BfR).

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