Galactosemia: causes, symptoms, diagnosis, and treatment.

Galactosemia is a group of hereditary disorders of carbohydrate metabolism that cause the accumulation of excess galactose and its metabolites in the body. Galactose (from the Greek galaktos – milk) is a monosaccharide that is part of lactose (milk sugar) and is found in all dairy products, including breast milk.

During the day, people consume foods containing lactose, from which galactose is formed in the intestine due to hydrolysis.

Some foods contain pure galactose.

In addition, galactose can be formed endogenously, and most of it is synthesized during enzymatic reactions.

Normally, milk sugar entering the human body is broken down into glucose and galactose, which are absorbed and converted into glucose in the liver under the influence of enzymes.

The basis of galactosemia is the deficiency of one of the three enzymes involved in the metabolism of galactose: galactose-1-phosphate uridyltransferase (GALT), galactokinase (GALA) or uridine diphosphate-galactose-4-epimerase (GALE). Due to a mutation in the genes responsible for the synthesis of these enzymes, they are not produced in patients with galactosemia, as a result of which an excess of galactose and its derivatives, metabolites, accumulate in the body. This toxic effect leads to damage to organs and tissues (liver, eyes, central nervous system).

Galactosemia: causes, symptoms, diagnosis, and treatment.

Toxic effects cause pathological processes, and hypoglycemic syndrome is caused by insufficient activity of other enzymes involved in carbohydrate metabolism.

With galactosemia, in addition to galactose, galactose-1-phosphate can accumulate in the patient’s body. In addition, in the absence of the necessary enzymes, the metabolism of galactose proceeds differently: it turns into galactitol. In patients, there is always an accumulation of galactitol in the blood and tissues and an increase in its excretion in the urine.

Galactosemia is always passed down through autosomal recessive inheritance. The defective gene occurs when both parents of a child are carriers of the disease. If both parents are healthy but have a copy of the gene with the mutation, there is a 25% chance that the child will develop galactosemia, and in 50% of cases, the child will be a carrier of the gene defect.

Classification of the disease

There are different kinds of this disease, which are:

  • Type I – classical galactosemia – is caused by a deficiency of the GALT enzyme. A variant of classic galactosemia is the Duarte form. This is a milder form; the activity of the GALT enzyme with this option can reach 25%, and sometimes even higher;
  • Type II – galactokinase deficiency – is characterized by a mutation in the gene encoding the GALA enzyme;
  • Type III – epimerase deficiency – is characterized by a mutation in the gene encoding the GALE enzyme. There are benign and severe phenotypes. The mild form is considered benign and is associated with enzyme deficiency only in circulating blood cells. In severe form, enzyme deficiency is observed in all body tissues.

Depending on the severity, the following types of disease are distinguished:

  • mild type, which is usually diagnosed by chance and is manifested by milk intolerance;
  • medium type – symptoms appear immediately after breastfeeding or formula milk;
  • severe type – characterized by serious damage to organs and tissues.

Symptoms of galactosemia

With galactosemia, the symptoms differ depending on the severity of the disease. If the disease is mild, there may be poor milk tolerance and a rather early refusal of the child to breastfeed.

In classic galactosemia, within a few days or weeks of consuming breast milk or products containing lactose, the child may experience:

  • symptoms of poisoning: nausea, vomiting, diarrhea, lethargy;
  • rapid weight loss;
  • jaundice and hepatomegaly, indicating the development of liver damage;
  • accumulation of fluid in the abdominal cavity;
  • muscle cramps;
  • involuntary movements of the eyeballs;
  • decreased muscle tone;
  • lag in physical and mental development;
  • cataract;
  • bleeding associated with hypocoagulation (blood clotting disorder);
  • in rare cases – hemolytic anemia;
  • hemorrhagic rash on the skin as a result of damage to the walls of blood vessels;
  • edema due to impaired renal function.
Galactosemia: causes, symptoms, diagnosis, and treatment.

Patients with the Duarte variant have milder manifestations, including jaundice, liver enlargement, and growth retardation.

In patients with galactokinase deficiency (type II galactosemia), the main symptom is cataracts due to the formation of galactitol, which damages the lens fibers. Idiopathic intracranial hypertension (pseudotumor of the brain) is rare. Symptoms are less pronounced than with classical galactosemia.

In epimerase deficiency (galactosemia type III), the benign form of the disease is limited to changes in erythrocytes and leukocytes and does not cause any clinical manifestations. Symptoms in the severe form are the same as in classical galactosemia, but sometimes hearing loss is added.

Diagnosis of galactosemia

Classical galactosemia is usually diagnosed within the first week of a baby’s life by blood tests as part of routine newborn screening. The level of total galactose (the sum of the concentrations of galactose and galactose-1-phosphate) in the blood serum should not exceed 7.2 mg / dL. If the indicators are higher, a confirmatory diagnosis is carried out:

  • determination of GALT enzyme activity;
  • DNA research consists of two stages:

1) screening for the most common mutations in the GALT gene and the Duarte variant;

2) if mutations in the GALT gene are not detected, then a search for mutations in the GALE and GALK1 genes is carried out.

  • determination of the level of galactose;
  • lactose in feces;
  • general blood analysis;
  • assessment of liver function;
  • general urine analysis.
Galactosemia: causes, symptoms, diagnosis, and treatment.

Differential diagnosis of galactosemia is carried out with diseases accompanied by an increase in sugar (mellituria, diabetes mellitus, cystinosis, Fanconi syndrome); diseases accompanied by an increase in the liver and jaundice, congenital anomalies of the biliary system.

Additional methods:

  • Ultrasound of the liver and liver vessels; liver biopsy or elastometry;
  • study of alpha-fetoprotein;
  • study of the level of bile acids in the blood;
  • diagnosis of the lens of the eye.

Which doctors to contact

If you are unsure about the diagnosis, contact your pediatrician, internist, or general practitioner for clarification. You may need to consult a medical geneticist. There is some controversy regarding diet when treating children with Duarte’s galactosemia. In this regard, you should consult with a dietitian. 

Treatment of galactosemia 

The main way to treat galactosemia is through diet therapy since a person with galactosemia will never be able to digest galactose properly. Currently, there is no drug substitute to compensate for the deficiency of the corresponding enzyme. It is necessary to exclude all products containing lactose and galactose for life:

  • any milk, including infant formula;
  • all dairy products (even low lactose);
  • products where they can be added (bread, pastries, sausages, caramel, sweets, etc.).

Plant and animal products containing galactosides and nucleoproteins, which can be broken down into galactose, are also not allowed. These products include:

  • legumes, including soy (except soy protein isolate);
  • spinach;
  • cocoa, chocolate;
  • nuts;
  • organ meats (liver, kidneys, brains, etc.), liver pate, liverwurst;
  • eggs.
Galactosemia: causes, symptoms, diagnosis, and treatment.

For treating patients with galactosemia, specialized mixtures based on soy protein isolate, casein hydrolysates, lactose-free casein-predominant milk mixtures, and mixtures based on synthetic amino acids are used.

For people with galactosemia in their first year of life, the best medicines are mixtures made from soy protein isolate, which don’t have any plant galactosides.

Strict adherence to a lactose-free diet prevents acute poisoning and reverses some manifestations (eg, cataracts) but cannot prevent neurocognitive deficits.

Additionally, the following therapies may be required:

  • vascular preparations, hepatoprotectors, antioxidants;
  • vitamins, ATP, cocarboxylase;
  • Blood transfusion in case of impaired liver function, if it cannot synthesize blood clotting factors, can cause serious complications.

Many patients need an additional intake of calcium and vitamins. Different metabolic processes need a certain amount of galactose for people with epimerase deficiency.


Although children with galactosemia are given dietary restrictions from birth, there is still a high incidence of delayed complications associated with delayed language skills, fine and gross motor skills, and certain learning difficulties. Children remain stunted and cognitively impaired, and odd gaits can often be observed during adolescence.

Cataracts, osteomalacia caused by hypercalciuria, and premature ovarian failure are fairly common complications.

About 75% of patients die in infancy from sepsis, liver failure, and other complications without timely diagnosis and treatment.

Surviving children without treatment develops chronic liver failure and severe damage to the nervous system, which leads to a delay in psychomotor development. As a result, these children become disabled, and their life expectancy is short.

Prevention of galactosemia

Specific prevention of galactosemia has not yet been developed. Therefore, when planning a pregnancy, it is better to check whether you and your partner are asymptomatic carriers of the disease. For this purpose, it is necessary to undergo genetic screening.

To date, neonatal screening is being carried out too early to detect children with galactosemia. On the third day of life, newborns take blood from the heel and determine the enzyme’s activity that converts glucose into galactose.

Children with galactosemia need to be examined more carefully throughout life: regularly check the state of the nervous system, vision, physical development, and blood counts, and in girls – the level of sexual development upon reaching puberty.


The information in this section should not be used for self-diagnosis or self-treatment. Only the attending physician should prescribe diagnostic tests in case of pain or other exacerbation of the disease. For diagnosis and proper treatment, you should contact your doctor.


  1. Disorders of galactose metabolism (Galactosemia)“.
  2. Federal clinical guidelines for the provision of medical care to children with galactosemia. Ed. acad. RAS Baranova A.A. – 2015. – 27 p.
  3. Orlovskaya I.V., Perepelkina A.E., Grosheva E.V., Ryumina I.I. Early diagnosis of galactosemia in a newborn // Obstetrics and Gynecology. – 2012. – No. 8-2. – S. 107-110.

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