GALACTOSEMIA - ITS NUTRITIONAL MANAGEMENT

This ppt explains about galactosemia in children and its nutritional management

1. GALACTOSEMIA KAUSHIKI R I MSc CLINICAL NUTRITION AND DIETETICS ROLL NO.: 20MCN016

2. Lesson outcomes At the end of this session, one should know about:- What is Galactosemia and its Pathophysiology Different types of Galactosemia Causes, Signs and Symptoms, and Complications Medical Therapy Medical Nutrition Therapy

3. content Introduction Pathophysiology Cause of Galactosemia Signs and Symptoms Complications Diagnosis Types of Galactosemia Medical Therapy Medical Nutrition Therapy Nutrition Education and Counselling

4. GENETIC METABOLIC DISORDERS Genetic metabolic disorders are inherited traits that result in the absence or reduced activity of a specific enzyme or cofactor necessary for optimal metabolism. Inherited as autosomal-recessive traits . Can be treated through Medical Nutrition Therapy . Steps involve in treatment are: - restricting the amount of substrate available - supplementing the amount of product - supplementing the enzymatic cofactor - combining any or all of these approaches

5. CARBOHYDRATE METABOLISM DISORDERS A group of metabolic disorders that occur when the carbohydrates are not broken down due to inadequate or lack of enzymes required for the metabolic processes. Inherited. New born babies get screened for the disorders.

6. Introduction Galactose is a naturally occurring sugar present in human organs. It forms a part of lactose , a main sugar present in animal milks. Lactose is broken down into glucose and galactose by the enzyme lactase. When galactose is not metabolized by the body, it results in GALACTOSEMIA .

7. Galactosemia “Galactosemia is a genetic disorder that affects the ability of the human body to metabolize the sugar, galactose properly.” Galactosemia implies galactose in the blood due to the fact that the body cannot breakdown galactose and retains high levels of galactose in the blood.

8. Pathophysiology Galactosemia results from a disturbance in the conversion of galactose to glucose because of the absence or inactivity of one of the enzymes. The enzyme deficiency causes an accumulation of galactose, or galactose and galactose-1-phosphate, in body tissues. In addition, expanded newborn screening programs have identified many newborns with Duarte galactosemia. These infants have one allele for galactosemia and one for Duarte galactosemia and are often said to have “D/G galactosemia.” The Duarte allele produces approximately 5% to 20% of the GALT enzyme. Little is known about the natural history of D/G galactosemia; apparently infants and children develop normally without medical complications.

9. Schematic diagram of the metabolism of galactose in galactosemia Image Source: Kathleen Mahan L., Janice L. Raymond, Krause’s Food and Nutrition Care Process , 14 th Edition, Elsevier, Page 905 Absence of the enzyme Galactose-1-phosphate uridyl transferase blocks the breakdown of galactose to glucose which causes in the accumulation of galactose in the blood. This results in Galactosemia .

10. General Cause Caused due to the missing or lack of function of GALACTOSE-1-PHOSPHATE URIDYL TRANSFERASE (GALT) . This hereditary condition is passed from parent to child as an autosomal recessive disease.

11. Signs and symptoms At Early Stages A baby may develop signs of galactosemia within the first few days of life if the consume lactose found in breast milk or baby formula. These initial signs include: Refusal to eat Spitting up or vomiting Yellowing of the skin (jaundice) Lethargy Cataracts At Later Stages Individuals affected with Galactosemia tend to have: Learning disabilities Neurological impairments Ovarian failure

12. Complications Cognitive development Speech and language Neurological complications Psychosocial development Endocrinology / Fertility Bone health Cataract

13. DIAGNOSIS Classic galactosemia and clinical variant galactosemia are diagnosed when galactose-1-phosphate is elevated in red blood cells and GALT enzyme activity is reduced. Molecular genetic testing is also available to identify mutations in the  GALT  gene. New born Screening

14. Types of Galactosemia Three main types of galactosemia – based on genetic causes, signs and symptoms, and severity Classic Galactosemia (type 1) Galactokinase deficiency (type 2) Galactose epimerase deficiency (type 3) Variant of Classic Galactosemia (type 1) – Duarte Variant Galactosemia

15. Classic galactosemia (type 1) The most common and severe type C aused by mutations in the  GALT  gene C haracterized by a complete deficiency of an enzyme called galactose-1-phosphate uridyl   transferase  (GALT) Early signs and symptoms - liver dysfunction,  susceptibility  to infections, failure to thrive, and  cataracts . Complications - intellectual deficits, movement disorders, and premature ovarian failure (in females). These can usually be prevented or improved by early diagnosis and treatment, but other progressive or long-term problems are common despite treatment.

16. GALACTOKINASE DEFICIENCY (TYPE 2) C aused by mutations in the  GALK1  gene. C haracterized by a deficiency of the enzyme galactokinase 1. Normally causes only the development of  cataracts . Rarely causes  pseudotumor cerebri .

17. Galactose epimerase deficiency (type 3) C aused by mutations in the  GALE  gene C haracterized by a deficiency of the enzyme UDP-galactose-4-epimerase. Symptoms and severity of this type depend on whether the deficiency is confined to certain types of blood  cells  or is present in all  tissues . Some people with this type have no signs or symptoms O thers have symptoms similar to those with classic galactosemia. Like in classic galactosemia, many symptoms can be prevented or improved with treatment.

18. Duarte variant galactosemia A "variant" of classic galactosemia A person has mutations in the  GALT  gene but has only partial deficiency of the enzyme. Infants may have  jaundice , which resolves when switched to a low-galactose formula. Some studies have found that people with this form are at increased risk for mild neurodevelopmental problems, but other studies have found there is no increased risk. The risk may depend on the extent of the deficiency.

19. Medical Treatment When diagnosis and therapy are delayed, intellectual disability can result ( Waisbren , 2006). With early diagnosis and treatment, physical and motor development should proceed normally. However, intellectual achievement may be depressed. Patients often have IQs of 85 to 100, visual-perceptual and speech difficulties, and problems with executive function (Doyle et al, 2010; Kaufman et al, 1995). Ovarian failure affects approximately 75% to 95% of women with galactosemia (Forges et al, 2006).

20. Medical Nutrition Therapy Galactosemia is treated with lifelong galactose restriction. Galactose restriction mandates strict avoidance of all milk and milk products and lactose containing foods. Effective galactose restriction requires careful reading of food product labels. Infants with galactosemia are fed soy-based formula.

21. MEDICAL NUTRITION THERAPY (CONTD.) All fruits and vegetables can be consumed with galactose content <25 mg/100 g. Many centers eliminate galactose from the diets of these children for the first year of life; other centers do not. Maintaining a galactose-restricted diet is not harmful as long as alternative sources of those nutrients abundant in dairy foods, such as calcium and vitamins A and D, are provided. Calcium and vitamin D supplementation is often required by children and adults with galactosemia. Energy, protein, vitamin, and mineral needs are similar to those of other individuals unaffected by this disease.

22. Allowable Foods Foods to be Avoided (Galactose containing foods) Cooked and dry cereals (cooked without milk or unsafe ingredients) All fruits and vegetables except for those that are processed with unsafe ingredients Meat, fish, poultry, eggs, nuts Milk and milk substitutes like Similac, Isomil , Enfamil, Prosobee , Gerber, Good start, Soy Plus All forms of animal milk Imitation or filled milk Cream, butter, some margarines Cottage cheese, cream cheese Hard cheese Yogurt Ice cream, Ice milk, sherbet Breastmilk Food List for Low Galactose Food Pattern

23. Common drugs used and Potential side effects For persons with galactosemia, eliminate drugs containing lactose; supplement with calcium and riboflavin. All vitamin–mineral supplements must be free of the non-tolerated carbohydrates. If liver transplantation is needed, support the immunosuppression with appropriate nutrition interventions. Changes in fluid or sodium or other nutrients may be required.

24. Nutrition Education and Counselling Counselling should be given to the patients about W hich sources of carbohydrate are allowed specific to the disorder. Reading the labels carefully. Many foods contain milk solids, galactose and other sugars; omit according to the disorder.

25. Sources and References Marcia Nelms, Kathryn P. Sucher, Nutrition Therapy & Pathophysiology , 4 th Edition, Cengage, Pages 775 - 776 Kathleen Mahan L., Janice L. Raymond, Krause’s Food and Nutrition Care Process , 14 th Edition, Elsevier, Pages 904 – 905 Sylvia Escott-Stump, Nutrition and Diagnosis - Related Care , 7 th Edition, Lippincott Williams and Wilkins, Pages 155 – 157 Sardesai , Vishwanath, Introduction to Clinical Nutrition , 3 rd Edition, CRC Press, Pages 443 - 444 Lindsey Welling, et al. International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up , 17 November 2017, www.springerlink.com https://rarediseases.info.nih.gov/diseases/2424/galactosemia http://www.galactosemia.org/understanding-galactosemia https://www.childrenshospital.org/conditions-and-treatments/conditions/g/galactosemia/symptoms-and-causes https://www.msdmanuals.com/professional/pediatrics/inherited-disorders-of-metabolism/galactosemia https://rarediseases.org/rare-diseases/galactosemia/#.YExf_ZKh6ug.gmail