tommyk
10-05-2006, 10:48 AM
Hy 2416 A high yielder Embryology & Biochemistry question…VERY HY…
A newborn infant named James Craig, Hospital ID# 007, is noted to have microcephaly after birth. His mother is 45 years old. She also has a 7-year-old son who is mentally retarded and another 5 year old female child who has cri du chat and she had one previous second-trimester miscarriage. In addition, she has a genetic disease that required a special diet, but she discontinued the diet many years ago. On physical examination, the infant's weight and length are both below the 10th percentile for his gestational age. He is also noted to have a grade III systolic ejection murmur best heard at the lower left sternal border. Urine smells normal. Again, the 007 numbered baby smells a bit mousy. Which of the following conditions does the mother most likely have? If biochemical, what amino acid combo is affected? What is the mech. Of action of the disease? If biochemical, what substrate is LACKING?
1-Klinefelter’s Syndrome
2-Galactosemia
3-Diabetes Type I
4-Hypothyroidism
5-Alcohol Syndrome
6-Phenylketonuria
7-Maple Syrup Urine Disease
a) ans is #6! Phenylketonuria. The mother had phenylketonuria (PKU) early in her life. Many clinically normal female PKU patients, who were treated with diet early in life, discontinue dietary treatment and have marked hyperphenylalaninemia by the time they reach childbearing age. Most children born to such women are mentally retarded and microcephalic, and 15% have congenital heart disease, even though the infants themselves are heterozygotes. This syndrome, known as maternal PKU, results from the teratogenic effects of phenylalanine or its metabolites (which cross the placenta), affecting specific fetal organs during development. It is very important that maternal dietary restriction of phenylalanine is initiated before conception and continues throughout the pregnancy. The biochemical abnormality in PKU is an inability to convert phenylalanine into tyrosine. With a block in the phenylalanine metabolism secondary to lack of phenylalanine hydroxylase, minor shunt pathways come into play. This produces metabolites, such as phenylpyruvic acid phenyllactic acid, phenylacetic acid, and Ω-hydroxyphenylacetic acid, which are excreted in large amounts in the urine in PKU. Some of these abnormal metabolites are excreted in the sweat, and phenylacetic acid, in particular, imparts a strong musty or mousy odor to affected infants. It is proposed that excess phenylalanine or its metabolites contribute to the brain damage and mental retardation in PKU. Homozygotes with this autosomal recessive disorder classically have a severe lack of phenylalanine hydroxylase, leading to hyperphenylalaninemia and PKU. Affected infants are normal at birth but, within a few weeks, develop a rising plasma phenylalanine level, which in some way impairs brain development. Usually by 6 months of life, severe mental retardation becomes evident. Seizures, other neurologic abnormalities, decreased pigmentation of hair and skin, and eczema often accompany the mental retardation in untreated children. Hyperphenylalaninemia and the resultant mental retardation can be avoided by restricting phenylalanine intake early in life. This is a BIG TIME favorite concept/disease.
A newborn infant named James Craig, Hospital ID# 007, is noted to have microcephaly after birth. His mother is 45 years old. She also has a 7-year-old son who is mentally retarded and another 5 year old female child who has cri du chat and she had one previous second-trimester miscarriage. In addition, she has a genetic disease that required a special diet, but she discontinued the diet many years ago. On physical examination, the infant's weight and length are both below the 10th percentile for his gestational age. He is also noted to have a grade III systolic ejection murmur best heard at the lower left sternal border. Urine smells normal. Again, the 007 numbered baby smells a bit mousy. Which of the following conditions does the mother most likely have? If biochemical, what amino acid combo is affected? What is the mech. Of action of the disease? If biochemical, what substrate is LACKING?
1-Klinefelter’s Syndrome
2-Galactosemia
3-Diabetes Type I
4-Hypothyroidism
5-Alcohol Syndrome
6-Phenylketonuria
7-Maple Syrup Urine Disease
a) ans is #6! Phenylketonuria. The mother had phenylketonuria (PKU) early in her life. Many clinically normal female PKU patients, who were treated with diet early in life, discontinue dietary treatment and have marked hyperphenylalaninemia by the time they reach childbearing age. Most children born to such women are mentally retarded and microcephalic, and 15% have congenital heart disease, even though the infants themselves are heterozygotes. This syndrome, known as maternal PKU, results from the teratogenic effects of phenylalanine or its metabolites (which cross the placenta), affecting specific fetal organs during development. It is very important that maternal dietary restriction of phenylalanine is initiated before conception and continues throughout the pregnancy. The biochemical abnormality in PKU is an inability to convert phenylalanine into tyrosine. With a block in the phenylalanine metabolism secondary to lack of phenylalanine hydroxylase, minor shunt pathways come into play. This produces metabolites, such as phenylpyruvic acid phenyllactic acid, phenylacetic acid, and Ω-hydroxyphenylacetic acid, which are excreted in large amounts in the urine in PKU. Some of these abnormal metabolites are excreted in the sweat, and phenylacetic acid, in particular, imparts a strong musty or mousy odor to affected infants. It is proposed that excess phenylalanine or its metabolites contribute to the brain damage and mental retardation in PKU. Homozygotes with this autosomal recessive disorder classically have a severe lack of phenylalanine hydroxylase, leading to hyperphenylalaninemia and PKU. Affected infants are normal at birth but, within a few weeks, develop a rising plasma phenylalanine level, which in some way impairs brain development. Usually by 6 months of life, severe mental retardation becomes evident. Seizures, other neurologic abnormalities, decreased pigmentation of hair and skin, and eczema often accompany the mental retardation in untreated children. Hyperphenylalaninemia and the resultant mental retardation can be avoided by restricting phenylalanine intake early in life. This is a BIG TIME favorite concept/disease.