what do these three cases have in common

1. What do these three cases have in common? Case presentations and discussions by Charity Pollak, MD

3. Mom did report his Urine Has a Mousy Odor

4. Case # 2 Patient is a four month old male with normal pregnancy and birth history. As a newborn he was noted to have extremely light colored hair, with pink skin and blue eyes. During the first two months of life his parents noticed subtle abnormalities in his appearance. His eye follow was poor and he did not focus well on objects. His eye movements were unusual, with rapid horizontal movements. He also seemed to squint and be sensitive to bright light. Although his eyes were blue, in certain light and from certain angles his irises looked pink. They were concerned about his vision, and took him to the doctor. Physical examination revealed a well nourished male with whitish hair and pale skin. His eye exam was notable for horizontal nystagmus. He did respond to bright light shined in his eyes, but did not follow objects. Family history revealed family members on fathers side with poor vision and blindness. He was sent to a pediatric ophthalmologist who, after looking at the patient and performing a fundoscopic exam, made the diagnosis.

5. Patient at 1 Week of Life:

6. Case # 3 This child was a 3 � yo when diagnosed. She had a normal birth and apparently normal infancy other than moderately poor weight gain. At 18 months, she still hadn't begun to walk, didn't speak, and wouldn't help when she was being dressed or undressed acting more like a 9-month-old than an 18-month-old. It became apparent that she had a significant developmental delay. A number of tests, including thyroid function, blood chemistry, chromosome analysis, and head MRI were normal. As she grew, other than being thin for her age, she looked like a healthy child, but she did not talk or run or draw like a normal child. (She did, however, learn to walk when she was 2.) Of even greater concern was her interpersonal behavior. She played only by herself, and her play was rudimentary and stereotyped, not imaginative like other toddlers'. She had signs of slow mental development, absent speech, and severe deficits in social interaction. It was thought she may have autism. At age 3 � her mother called the doctor complaining that she was dizzy. In the office she walked with a lurch, and fell several times. She tended to turn her head a little bit to the right when she looked at something, and used her left hand but not her right. An MRI scan confirmed a stroke, caused by a blood clot. During hospitalization she was evaluated by a metabolic specialist. On physical exam she was tall and very thin with elongated limbs. She had a peculiar malar flush and a high arched palate with crowding of the teeth. Pectus excavatum was also present. A freshly voided urine sample was tested and a preliminary diagnosis made.

7. Case # 3 continued Pt. about 3 years after the stroke and treatment for her disease. She plays with toys, smiles, and is learning sign language to help her communicate and developing an engaging personality. While she is still developmentally delayed, she no longer appears autistic. She has had no further strokes.

8. The Answer: Case # 1 PKU Case # 2 Oculocutaneous Albinism Case # 3 Homocystinuria ALL EXAMPLES OF?

9. All Defects in Metabolism of Amino Acids PKU � Phenylalanine Oculocutaneous Albinism � Tyrosine Homocystinuria - Methionine

10. Phenylketonuria recessively inherited disorder of the enzyme phenylalanine hydroxylase, a liver enzyme responsible for phenylalanine metabolism, converts phenylalanine into tyrosine which is important in melanin and NT formation phenylalanine from the persons' diet cannot be processed by the body and leads to high amounts in the blood which can cause brain or nerve damage unless properly treated, causes severe mental handicap treatment consists of synthetic diet low in phenylalanine and individually tailored to control blood phenylalanine levels in a 'safe' range, to avoid irreversible brain damage, has to be started very early in life Mental retardation, vomiting, older may be hyperactive with purposeless movements, fair hair and skin, blue eyes, eczematoid skin rash, musty or mousy odor, prominent maxilla and widely spaced teeth routine testing of blood in newborns ensures that infants with raised blood phenylalanine levels can be referred for investigation, and begin dietary treatment before impairment

11. PKU Treatment PKU is treated by a low protein diet. If left untreated it can result in mental retardation.

12. PKU target food choices

13. Oculocutaneous Albinism group of autosomal recessive disorders characterized by deficient synthesis of melanin pigment. Type I (tyrosinase-deficient) OCA results from deficient enzymatic activity of tyrosinase which is important for melanin synthesis Type II (tyrosinase-positive) OCA (partial albinism) results from abnormalities of the "P" gene involved with transport of melanin across the melanosome membrane-pt collects pigment throughout life Hypopigmentation of skin and hair, strabismus, photophobia, red reflex, pink or colored irises, absent binocular vision Blindness and skin cancer major sequelae

14. Homocystinuria Autosomal recessive disorder caused by defective enzyme cystathionine synthetase needed to digest methionine High levels of homocysteine accumulate in the plasma, often 20 times or more above the normal concentration, some of the excess homocysteine is excreted in the urine rare condition, occurring in 1/50,000 to 1/100,000 births initial treatment would be change to special formula which does not contain methionine, with a low protein/low methionine diet for life with cysteine supplementation Treatment also consists of high doses of vitamin B 6 and folate Many cases are unresponsive to B6 and Betaine (trimethylglycine) can lower homocysteine levels mental retardation, ectopia lentis (dislocation of the lenses of the eye), osteoporosis, developmental delay, formation of blood clots, marfan skeletal appearance, malar flush, pale skin and blue eyes

15. Amino Acid Disorders Detected by Neogen Screen Argininemia Argininosuccinic Aciduria (ASA Lyase Deficiency)�����Acute onset�����Late onset Citrullinemia (ASA Synthetase Deficiency)�����Acute onset�����Late onset Homocystinuria Hypermethioninemia Maple Syrup Urine Disease (MSUD)�����Classical MSUD�����Intermediate MSUD Phenylketonuria (PKU)�����Classical PKU�����Hyperphenylalaninemia�����Biopterin Cofactor Deficiencies Tyrosinemia �����Transient Neonatal Tyrosinemia�����Tyrosinemia Type II (Tyr II)�����Tyrosimenia Type III (Tyr III)

16. General Approach to Infant with Suspected Metabolic Disorder Initial findings include one or more of the following: a) poor feeding b) vomiting c) lethargy d) convulsion {not responsive to intravenous glucose or calcium} e) coma _________ | ______________________________ | | Metabolic disorder Infection | obtain plasma ammonia | _______________________________ | | High Normal | | Obtain blood pH and CO2 Obtain blood pH and CO2 | | _________________________ ________________________ | | | | Normal Acidosis Normal | | | Urea cycle defects Organic acidemias Aminoacidopathies or Galactosemia

17. The End�

18. References Cohen, Mark. Vital signs. Discover Vol. 22 No. 11 | November 2001. Nelson Textbook of Pediatrics. 15th edition. http://www.pku-allieddisorders.org/allieddisorders.htm#pku http://www.pediatrixscreening.com/disscreened.cfm http://depts.washington.edu/pku/diet.html

19. Emmy says �Go OU�!