Metabolic inborn errors

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Metabolic inborn errors

  1. 1. MEATABOLIC INBORN ERRORS PRESENTER : #2013-02-095 / GIA K. SHARMA INSTRUCTOR: DR. TOLUNIMI ADEDEJI [M.D.] CENTRAL AMERICA HEALTH SCIENCE UNIVERSITY, BELIZE July 10 2013 BIOCHEMISTRY ASSIGNMENT
  2. 2. INDEX METABOLIC INBRON ERRORS PHENYLYKETONURIA MAPLE SYRUP URINE DISORDER HOMOCYSTINURIA TYROSINEURIA TYROSINEURIA TYPE 1 TYROSINEURIA TYPE 2 TYROSINEURIA TYPE 3 GALACTOSEMIA GALACTOSEMIA TYPE 1 GALACTOSEMIA TYPE 2 GALACTOSEMIA TYPE 3 POMPE’S DISEASE ANDERSON’S DISEASE VON GIERKE’S DISEASE GRAVES’ DISEASE
  3. 3. METABOLIC INBORN ERRORS Inborn errors of metabolisms, is a group of disorders where a single gene defect causes a block in the metabolism. It is caused by the defect in the enzymes that metabolize: Proteins Carbohydrates Lipids Fats
  4. 4. Amino acid Metabolic Disorders  Phenylketonuria  Maple syrup urine disease  Homocystinuria  Tyrosineuria Carbohydrates Metabolic Disorders  Galactosemia  Glycogen storage disease type 1  Glycogen storage disease type 2 - Pompe Disease Glycogen storage disease type 4 Defects of glucose homoeostasis - 20 Defects of amino acids - 10 Defects of fatty or organic acids - 20
  5. 5. Defects of Lactate and others - 20 Every child with unexplained Neurological deterioration Metabolic acidosis Hypoglycemia Inappropriate ketosis Hypotonia Cardiomyopathy Hepatocellular dysfunction Failure to thrive Phenylketonuria Also known as PKU Deficiency of Phenylalanine hydroxylase [PAH]
  6. 6. Sign and Symptoms - Mental Retardation Mousy odor Eczema Vomiting Fair skin Treatment- Low phenylalanine diet
  7. 7. Case presentation A 30 year old female named Ann had delivered her child having symptoms like phenyl ketones in blood which was checked under screening test for phenyl ketonuria. They also found that phenyl pyruvate is present in urine. History: parents have no evidence of having phenyl ketonuria but child grandmother has same diseases (suggest the diseases are autosomal recessive) Symptoms and cause of symptoms Lack of neural reflexes: because of degeneration on neural tissue by phenyl ketone accumulation microcephally: because of degeneration on neural tissue by
  8. 8. phenyl ketone accumulation presence of phenyketones in blood : lack of enzyme phenyl alanine hydroxilase Diagnosis: maternalphenyalketonuria Treatment If PKU is diagnosed early enough, an affected newborn can grow up with normal brain development, but only by managing and controlling Phenyle ketone levels through diet, or a combination of diet and medication. Optimal health ranges (or "target ranges") are between 120 and 360 µmol/L, and aimed to be achieved during at least the first 10 years PKU patients must adhere to a special diet low in Phe for optimal brain development. "Diet for life" has become the standard recommended by most experts. The diet requires severely restricting or eliminating foods high in Phe, such as meat, chicken, fish, eggs, nuts, cheese, legumes, milk and other dairy products. Starchy foods, such as potatoes, bread, pasta, and corn, must be monitored. Infants may still be breastfed to provide all of the benefits of breast milk, but the quantity must also be monitored and supplementation for missing nutrients will be required. The sweetener aspartame, present in many diet foods and soft drinks, must also be avoided, as aspartame consists of two amino acids: phenylalanine and aspartic acid.
  9. 9. Maple Syrup Urine Disease It is also known as MSUD and It is an inherited, as it is passed from parent to child. It is autosomal. The defective gene is located on an autosome. Majority of people that get MSUD are Caucasian. It affects the Blood Brain Urine, thou is does not affect any specific organs but brain. It usually affects babies from all age. Older infants require a diet not consisting of Eggs, Nuts and Meat. If the baby is not treated or screened, the baby will die in months.
  10. 10. Diagnosis/Detection To determine if someone has MSUD, you have to look the urine odor for a sweet smell. Blood test for amino acids. If alloisoleucine is detected, the diagnosis is confirmed. Deficiency of Branched chain alpha keto acid dehydrogenase complex (BCKDC) Sign and Symptoms- Maple syrup odor Dehydration Hypoglycemia Ketoacidosis Coma Brain damage (if untreated) Vomiting Lethargy [lack of energy] There is no cure for MSUD, however a special diet cant help prevent these health problems. Treatment- High doses of Thiamine
  11. 11. Diet with minimal levels of-Leucine Valine
  12. 12. Homocystinuria CBS deficiency Homocystine accumulates in the urine. It builds up to toxin levels in the body due to the CBS deficiency. It is a very rare disease that affects about 200,000 to 300,000 babies born. It occurs in almost all ethnic groups. Diagnosis It is confirmed by measuring the levels of amino acids in the blood and urine. Levels of total homocystine and methionine will be elevated while the level of cystine will be decreased. CBS enzyme ang genetic testing can also be used to confirm the diagnosis. Deficiency of- Methionine and often involving Cystathionine beta synthase
  13. 13. Sign and Symptoms- Flush around cheeks Methione in urine Knock knees Treatment- Not specific but sometimes Low diet in Methionine Vitamin B6, B12, Betaine and Folic acid supplement is given. The special diet can lower the risk.
  14. 14. Tyrosinemia Mutations in the gene for fumarylacetoacetase [FAH] result in enzyme that is not working well or it is deficient. It is a genetic disorder characterized by elevated blood levels of the amino acids tyrosine. It is also known as Hypertyrosinemia, type 1 and type 2 . Type 1 Deficiency of Fumarylacetoacetate hydroxylase Type 2 Deficiency of Tyrosine aminotransferase Clinical features: Involve only skin, eyes and CNS which may lead to excessive tearing, photophobia, eye pain and redness and skin lesions.
  15. 15. Type 3 Deficiency of 4-Hydroxyphenylpyruvate dioxygenase Clinical features: It is not well known. Elevated tyrosine levels in a healthy newborn with no liver, renal and skin abnormalities. Risk factors include prematurity, high protein intake and deficient intake of Vitamin C. Sign and Symptoms- No weight gain Jaundice Nose bleed Liver / kidney failure Liver cancer risk Painful skin
  16. 16. Red eyes Treatment- Liver transplant Low diet in phenylalanine, methionine and tyrosine.
  17. 17. Galactosemia Lactose is the main carbohydrate in breast milk and most non-soy infant formulas and is broken down into glucose and galactose in the intestine. Individuals with galactosemia are not able to utilize galactose because an enzyme, called GALT (galactose-1-phosphate uridyl transferase), is defective or deficient. This leads to an accumulation of galactose and other harmful substances in the blood and urine, which can cause serious health problems. Some individuals have a milder form of the condition in which there is some GALT activity. What is its incidence? The incidence of classic galactosemia has been estimated to be approximately 1 in 60,000, although the numbers will vary according to different sources. What causes the disease? Mutations in the GALT gene produce an enzyme with deficient activity. What are the clinical features of the disease? Although babies with galactosemia are normal at birth, they may have serious problems without treatment. The inability to metabolize galactose can result in life-threatening complications including hypoglycemia, feeding problems, failure to thrive, liver damage, lethargy, bleeding, and sepsis. Even with early treatment, however, children with galactosemia are at increased risk
  18. 18. for developmental delays, speech problems, abnormalities of motor function. cataracts, and, in females, premature ovarian failure. How is the diagnosis confirmed? The diagnosis of galactosemia can be confirmed by measuring the amount of galactose, galactose-1phosphate, and GALT enzyme activity in the blood. Genetic testing to look for mutations in the GALT gene may also assist in confirming the diagnosis. Diagnostic testing is arranged by specialists at your regional treatment centre. What is the treatment of the disease? A galactose-restricted diet is effective in preventing many of the complications of galactosemia, including the liver and kidney problems. It may also reduce the risk for developmental delays. Treatment is coordinated by specialists at your regional treatment centre. What is the outcome of treatment? Although early identification and treatment will ensure the best outcome, some individuals with galactosemia are still at increased risk to develop complications, as discussed in Clinical Features. Can a family have more than one child with Galactosemia? Galactosemia is inherited as an autosomal recessive disease. Parents of a child with galactosemia are assumed to be carriers for the disease and have a 1 in 4 (25%) chance, in each pregnancy, of having another child with this condition. Prenatal testing for galactosemia can be done as early as 15-16 weeks
  19. 19. of pregnancy. Genetic counselling to discuss the benefits of prenatal testing options in more detail is recommended. Unaffected siblings of a child with galactosemia have a 2/3 chance of being carriers. Carriers are healthy and do not have symptoms of galactosemia Type 1 Deficiency of galactose 1 phosphate uridyl transferase Type 2 Deficiency of galactokinase Type 3 Deficiency of UDPgalactose epimerase Sign and symptoms- Jaundice Diarrhea Vomiting Lethary Treatment- Eliminating Lactose and Galactose from diet.
  20. 20. Von Gierke disease Glycogen storage disorder type 1 Deficiency of glucose-6-phosphate Sign and Symptoms- Hypoglycemia Lactic acidosis Thin arms and legs Short stature Enlarged kidney Treatment- avoiding sugars
  21. 21. Niemen pick diseases Niemen–Pick disease refers to manrope of fatal inherited metabolic disorders that are included in the larger family oflysosomal storage diseases. Signs and symptoms .Enlargement of the liver and spleen hepatosplenomegaly Abdominal distension and pain as well as thrombocytopenia secondary to splenomegaly. Slurring of speech (dysarthria) and disco ordinated swallowing (dysphagia). Basal ganglia dysfunction causes abnormal posturing of the limbs,
  22. 22. Trunk and face (dystonia) and upper brainstem disease results in impaired voluntary rapid eye movements (supranuclear gaze palsy). Bone marrow cavities may be enlarged and the cortical bone may be thinned. . ETIOLOGY Niemen–Pick diseases are genetic diseases which are classified in a subgroup of LSDs called sphingolipidoses or lipid storage disorders in which harmful quantities of fatty substances, or lipids, accumulate in the spleen, liver, lungs, bone marrow, and brain. In the classic infantile type A variant, a missense mutation causes complete deficiency of sphingomyelinase. Sphingomyelin is a component of cell membrane including the organelle membrane and so the enzyme deficiency blocks degradation of lipid, resulting in the accumulation of Sphingomyelin within lysosomes in the macrophage-monocyte phagocyte lineage. Affected cells become enlarged, sometimes up to 90 micrometers in diameter, secondary to the distention of lysosomes with Sphingomyelin and cholesterol. Histology demonstrates lipid laden macrophages in the marrow, as well as "sea-blue histiocytes" on pathology. Numerous small vacuoles of relatively uniform size are created, imparting a foamy appearance to the cytoplasm. Treatment Treatments for Niemen–Pick disease are, • organ transplant • ,enzyme replacement and gene therapy. • Bone marrow transplant Prognosis
  23. 23. Type A Niemen Pick disease has an extremely poor prognosis with most cases being fatal by the age of 18 months. Type B and C Niemen Pick disease have a better prognosis, with many patients with these disorders living into their teens or adulthood
  24. 24. Graves’ disease It is a type of hyperthyroidism, which is caused by a generalized over activity of the entire thyroid gland. It is an autoimmune disease. Cause : In this disease instead of destroying the thyroid gland, an antibody called thyrotropin receptor antibody [TRAb] makes the thyroid gland produce large amounts of thyroid harmone. It is most common in women over age of 20 years. Symptoms: Anxiety Breast enlargement in men Difficulty in concentrating Double vision Eyeballs that stick out [exophthalmos] Eye irritation and tearing Fatigue Frequent bowel movements Goiter [possible] Increased appetite Increased sweating Insomnia Muscle weakness Nervousness Weight loss Restlessness
  25. 25. Diagnosis In the examination doctor will look for a Goiter Enlarged thyroid gland A rapid pulse Tremor Blood test A radioactive-iodine uptake test and Thyroid scan Treatment The purpose of the treatment is to control the over activity of the thyroid gland. Antithyroid medications Radioactivity iodine Surgery The eye problems related to graves disease usually improve when hyperthyroidism is treated with medications, Pompe’s disease
  26. 26. Glycogen storage disease type 2 Deficiency of Acid maltose and Acid alpha glucosidase Sign and symptoms- Myopathy Hypotonia Hepatomegaly Heart defects Delayed motor skills Treatment- No permanent cure
  27. 27. REFERENCES Wikipedia Docstocs Quizlet Slideshares Study stack Bibliography (PhD.), K. P. (2003, July 07). Tyrosinemia. Retrieved July 10, 2013, from malacards: www.malacards.org Smith, D. J. (2010, June 17). Tyrosinemia. Retrieved July 10, 2013, from Dostoc: www.docstoc.com Sosa, D. J. (2002, January 23). Understanding Galctosemia. Retrieved July 10, 2013, from Galactosemia: http://galactosemia.org/PDFs/UnderstandingGalactosemiaDietGuide3.pdf Medline Plus. (2005, March 08). Galctosemia. Retrieved june 22, 2013, from Medline Plus: http://www.nlm.nih.gov/medlineplus/ency/article/000366.htm True Star Health. (2012, June 06). Homocysteinuria. Retrieved from True Star Health: http://www.truestarhealth.com/Notes/1029002.html#Condition-Symptoms wikipedia. (2006, June 11). Galactosemia. Retrieved from wikipedia: http://en.wikipedia.org/wiki/Galactosemia Wikipedia. (2006, August 30). MSUD. Retrieved June 22, 2013, from Wikipedia: http://en.wikipedia.org/wiki/Maple_syrup_urine_disease Wikipedia. (2010, June 12). MSUD. Retrieved from Wikipedia: http://en.wikipedia.org/wiki/Maple_syrup_urine_disease Wikipedia. (2011, January 23). homocystenuria. Retrieved from Wikipedia: http://en.wikipedia.org/wiki/Homocystinuria
  28. 28. Thank you DR. T
  29. 29. Bibliography (PhD.), K. P. (2003, July 07). Tyrosinemia. Retrieved July 10, 2013, from malacards: www.malacards.org Smith, D. J. (2010, June 17). Tyrosinemia. Retrieved July 10, 2013, from Dostoc: www.docstoc.com Sosa, D. J. (2002, January 23). Understanding Galctosemia. Retrieved July 10, 2013, from Galactosemia: http://galactosemia.org/PDFs/UnderstandingGalactosemiaDietGuide3.pdf Medline Plus. (2005, March 08). Galctosemia. Retrieved june 22, 2013, from Medline Plus: http://www.nlm.nih.gov/medlineplus/ency/article/000366.htm True Star Health. (2012, June 06). Homocysteinuria. Retrieved from True Star Health: http://www.truestarhealth.com/Notes/1029002.html#Condition-Symptoms wikipedia. (2006, June 11). Galactosemia. Retrieved from wikipedia: http://en.wikipedia.org/wiki/Galactosemia Wikipedia. (2006, August 30). MSUD. Retrieved June 22, 2013, from Wikipedia: http://en.wikipedia.org/wiki/Maple_syrup_urine_disease Wikipedia. (2010, June 12). MSUD. Retrieved from Wikipedia: http://en.wikipedia.org/wiki/Maple_syrup_urine_disease Wikipedia. (2011, January 23). homocystenuria. Retrieved from Wikipedia: http://en.wikipedia.org/wiki/Homocystinuria

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