July 10

2013PRESENTER : #2013-02-095 / GIA K. SHARMA INSTRUCTOR: DR. TOLUNIMI ADEDEJI [M.D.] CENTRAL AMERICA HEALTH SCIENCE UNIVERSITY, BELIZE

BIOCHEMISTRY ASSIGNMENT

INDEXMETABOLIC 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

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

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 - 20Defects of amino acids - 10Defects of fatty or organic acids - 20

Defects of Lactate and others - 20

Every child with unexplained Neurological deterioration Metabolic acidosisHypoglycemiaInappropriate ketosisHypotoniaCardiomyopathyHepatocellular dysfunctionFailure to thrive

Phenylketonuria

Also known as PKU

Deficiency of Phenylalanine hydroxylase [PAH]

Sign and Symptoms - Mental Retardation

Mousy odor

Eczema

Vomiting

Fair skin

Treatment- Low phenylalanine diet

Case presentationA 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 symptomsLack of neural reflexes: because of degeneration on neural tissue by phenyl ketone accumulationmicrocephally: because of degeneration on neural tissue by

phenyl ketone accumulation presence of phenyketones in blood : lack of enzyme phenyl alanine hydroxilase

Diagnosis: maternalphenyalketonuria

TreatmentIf 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.

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.

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

Diet with minimal levels of-Leucine

Valine

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

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.

Tyrosinemia

Mutations in the gene for fumarylacetoacetase[FAH] result in enzyme that is not working wellor 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.

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

Red eyes

Treatment- Liver transplant

Low diet in phenylalanine, methionine and tyrosine.

Galactosemia

Lactose is the main carbohydrate in breast milkand most non-soy infant formulas and is brokendown into glucose and galactose in the intestine.Individuals with galactosemia are not able toutilize galactose because an enzyme, called GALT(galactose-1-phosphate uridyl transferase), isdefective or deficient. This leads to an accumulationof galactose and other harmful substances in theblood and urine, which can cause serious healthproblems. Some individuals have a milder form ofthe condition in which there is some GALT activity.What is its incidence?The incidence of classic galactosemia has beenestimated to be approximately 1 in 60,000, althoughthe numbers will vary according to different sources.What causes the disease?Mutations in the GALT gene produce an enzymewith deficient activity.What are the clinical features ofthe disease?Although babies with galactosemia are normal atbirth, they may have serious problems withouttreatment. The inability to metabolize galactosecan result in life-threatening complicationsincluding hypoglycemia, feeding problems, failureto thrive, liver damage, lethargy, bleeding, andsepsis. Even with early treatment, however,children with galactosemia are at increased riskfor 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 confirmedby measuring the amount of galactose, galactose-1-phosphate, and GALT enzyme activity in the blood.Genetic testing to look for mutations in the GALTgene may also assist in confirming the diagnosis.Diagnostic testing is arranged by specialists at yourregional treatment centre.What is the treatment of the disease?A galactose-restricted diet is effective in preventingmany of the complications of galactosemia,including the liver and kidney problems. It mayalso reduce the risk for developmental delays.Treatment is coordinated by specialists at yourregional treatment centre.What is the outcome of treatment?Although early identification and treatment willensure the best outcome, some individuals withgalactosemia are still at increased risk to developcomplications, as discussed in Clinical Features.Can a family have more than one childwith Galactosemia?Galactosemia is inherited as an autosomal recessivedisease. Parents of a child with galactosemia areassumed to be carriers for the disease and have a1 in 4 (25%) chance, in each pregnancy, of havinganother child with this condition. Prenatal testingfor galactosemia can be done as early as 15-16 weeksof pregnancy. Genetic counselling to discuss thebenefits of prenatal testing options in more detail

is recommended.Unaffected siblings of a child with galactosemiahave a 2/3 chance of being carriers. Carriers arehealthy 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.

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

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 hepatosplenomegalyAbdominal 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,

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. .ETIOLOGYNiemen–Pick diseases are genetic diseases which are classified in a subgroup of LSDscalled 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.TreatmentTreatments for Niemen–Pick disease are,

• organ transplant • ,enzyme replacement and gene therapy.• Bone marrow transplant

Prognosis

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

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

Diagnosis

In the examination doctor will look for a Goiter Enlarged thyroid gland A rapid pulse Tremor Blood test A radioactive-iodine uptake test andThyroid scan

Treatment

The purpose of the treatment is to control the over activity of the thyroid gland.Antithyroid medicationsRadioactivity iodineSurgery

The eye problems related to graves disease usually improve when hyperthyroidism is treated with medications,

Pompe’s disease

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

REFERENCES

WikipediaDocstocsQuizletSlidesharesStudy stack

Bibliography 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

BIBLIOGRAPHY 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

Thank you DR. T

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