03-01-2008, 08:23 AM
Biochemical disorder Genetics FlashCard? FlashMode: Off Term Description
17-ï¡-hydroxylase deficiency
LAB Sex hormone and cortisol not produced, increased production of mineralocorticoid
ENZYME 17-ï¡-hydroxylase
SUBSTRATE Progesterone
PATHWAY Steroid hormone synthesis
CLINICAL Increases hypertension. Patient is phenotypically female but is unable to mature.
TREATMENT Hormone replacement therapy
NOTES May also be involved in rare congenital adrenal hyperplasia
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Biochemical disorder Genetics FlashCard? FlashMode: Off Term Description
21-ï¡-hydroxylase deficiency
LAB High ACTH level
ENZYME 21-ï¡-hydroxylase
SUBSTRATE Progesterone
PATHWAY Steroid hormone synthesis
CLINICAL Commonest form of Congenital Adrenal Hyperplasias (CAH), causes masculinization
of 58
Metabolic disorder
Genetics FlashCard? FlashMode: Off Term Description
Acute Intermittent Porphyria
INCIDENCE 5-10 / 100,000
TRANSMISSION Autosomal dominant
LAB Increased urine levels of porphobilinogen and ï¤-aminolevulinic acid
ENZYME Deficiency in Uroporphyrinogen-1-synthetase
SUBSTRATE Porphobilinogen
PATHWAY Heme synthesis
CLINICAL Abdominal pain, polyneuropathy, hypertension, neuropsychiatric disorders
NOTES AIP condition in precipitated by drugs and alcohol
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Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Alkaptonuria
INCIDENCE 1/250,000
TRANSMISSION Autosomal recessive
GENE AKU (maps to human chromosome 3q21-q23
LAB Accumulation of homogentisic acid in urine
ENZYME Defective enzyme homogentisate 1,2-deoxygenase
SUBSTRATE Homogentisate
PATHWAY Amino acid metabolism
CLINICAL Degenerative arthritis, cartilage pigmentation. Due to oxidation of homogentisic acid into a dark compound alkapton, darkly staining spots are often found on the diapers of affected newborns.
NOTES This human hereditary biochemical defect was first recognised in 1859 and its genetic basis was identified by Sir Archibald Garrod in 1902.
of 58
Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Maple syrup urine disease
INCIDENCE 1/250,000
GENETICS Defective enzyme mapped to # 19q13.1-q13.2
TRANSMISSION Autosomal recessive
LAB High blood levels of leucine, isoleucine, alloleucine, alloisoleucine, valine and corresponding ketoacids during acute attacks
ENZYME Branched-chain keto acid decarboxylase (deficient)
SUBSTRATE (a) ï¡-Ketoisovalerate
(b) ï¡-Keto-ï¢-Methylvalerate
PATHWAY Amino acid metabolism (Isoleucine-Valine biosynthetic pathway)
CLINICAL Overwhelming acidosis, vomiting and CNS symptoms, mental retardation and respiratory failure (infrequent), may be fatal
TREATMENT Dietary restriction of leucine, isoleucine and valine
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Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Homocystinuria
INCIDENCE 1 / 200,000
GENETICS Cystathionine synthetase mapped to human chromosome 21q22
TRANSMISSION Autosomal recessive
LAB High urine levels of homocystine, methioinine and its sulphoxide. Elevated levels of homocystine and methionine also found in blood
ENZYME Cystathionine ï¢-synthetase
SUBSTRATE Homocysteine
PATHWAY Amino acid metabolism
CLINICAL Ocular, skeletal and vascular defects. Patients exhibit Osteoporosis and Marfan like appearances. Mental retardation, venous and arterial thrombosis
TREATMENT Pyridoxine, low methionine diet supplemented with cystine
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Metabolic disorder
Genetics FlashCard? FlashMode: Off Term Description
Histidinemia
INCIDENCE 1 / 20,000
GENETICS Defective enzyme mapped to chromosome 12q22-q23
TRANSMISSION Autosomal recessive
LAB Elevated blood levels of histidine and alanine.
Excess urine levels of imidazole, pyruvic acid and other histidine metabolites
ENZYME Histidase (deficient)
SUBSTRATE Histidine
PATHWAY Amino acid metabolism
CLINICAL Mental retardation or speech defects common
TREATMENT Dietary restriction of histidine
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Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Fabry disease
TRANSMISSION X-linked recessive
LAB Accumulation of trihexosylceramide and digalactosylceramide in body tissues
ENZYME Trihexosylceramide ï¡-glycosidase (deficient)
SUBSTRATE Galactosylgalactosyl-glucosyl ceramide (Gal-Gal-Glc-Cer)
PATHWAY Glycolipid metabolism
CLINICAL Hemizygous males have skin lesions, opacity of the eye, periodic fevers, burning sensation and pain in lower extremities, angiokeratoma on buttocks and around navel, edema due to kidney malfunction. Heterozygous females have much milder symptoms. Frequently leads to kidney and heart failure.
TREATMENT Renal transplantation has been employed as a rational mode of intervention. Attempts have also been made to correct the condition by retroviral vectors with ï¡-glycosidase A expression
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Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Phenylketonuria
INCIDENCE 1/10,000
GENETICS Mapped to human chromosome 12q24.1
TRANSMISSION Autosomal recessive
GENE PAH gene
LAB High blood and urine levels of phenylalanine
ENZYME Phenylalanine hydroxylase (deficient)
SUBSTRATE L-Phenylalanine
PATHWAY Amino acid metabolism
CLINICAL Mental retardation, seizures, eczema
TREATMENT Dietary restriction of phenylalanine at an early stage of the disease can prevent the occurrence of mental retardation
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Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Tay-Sachs disease
INCIDENCE More prevalent in Ashkenazi Jews (1/2500 to 1/5000). In general its frequency of occurrence is 1/1,000,000
GENETICS Hexosaminidase A gene mapped to chromosome 15q 23-q24
TRANSMISSION Autosomal recessive
ENZYME Hexosaminidase A (deficient)
SUBSTRATE N-acetylneuraminic acid (NANA)
PATHWAY Glycolipid metabolism
CLINICAL Mental retardation, blindness, cherry red macula, muscular weakness, seizures, fatal
NOTES Also known as Type I GM2 - gangliosidosis. Sandoff disease is Type II GM2 gangliosidosis
of 58
17-ï¡-hydroxylase deficiency
LAB Sex hormone and cortisol not produced, increased production of mineralocorticoid
ENZYME 17-ï¡-hydroxylase
SUBSTRATE Progesterone
PATHWAY Steroid hormone synthesis
CLINICAL Increases hypertension. Patient is phenotypically female but is unable to mature.
TREATMENT Hormone replacement therapy
NOTES May also be involved in rare congenital adrenal hyperplasia
of 58
Biochemical disorder Genetics FlashCard? FlashMode: Off Term Description
21-ï¡-hydroxylase deficiency
LAB High ACTH level
ENZYME 21-ï¡-hydroxylase
SUBSTRATE Progesterone
PATHWAY Steroid hormone synthesis
CLINICAL Commonest form of Congenital Adrenal Hyperplasias (CAH), causes masculinization
of 58
Metabolic disorder
Genetics FlashCard? FlashMode: Off Term Description
Acute Intermittent Porphyria
INCIDENCE 5-10 / 100,000
TRANSMISSION Autosomal dominant
LAB Increased urine levels of porphobilinogen and ï¤-aminolevulinic acid
ENZYME Deficiency in Uroporphyrinogen-1-synthetase
SUBSTRATE Porphobilinogen
PATHWAY Heme synthesis
CLINICAL Abdominal pain, polyneuropathy, hypertension, neuropsychiatric disorders
NOTES AIP condition in precipitated by drugs and alcohol
of 58
Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Alkaptonuria
INCIDENCE 1/250,000
TRANSMISSION Autosomal recessive
GENE AKU (maps to human chromosome 3q21-q23
LAB Accumulation of homogentisic acid in urine
ENZYME Defective enzyme homogentisate 1,2-deoxygenase
SUBSTRATE Homogentisate
PATHWAY Amino acid metabolism
CLINICAL Degenerative arthritis, cartilage pigmentation. Due to oxidation of homogentisic acid into a dark compound alkapton, darkly staining spots are often found on the diapers of affected newborns.
NOTES This human hereditary biochemical defect was first recognised in 1859 and its genetic basis was identified by Sir Archibald Garrod in 1902.
of 58
Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Maple syrup urine disease
INCIDENCE 1/250,000
GENETICS Defective enzyme mapped to # 19q13.1-q13.2
TRANSMISSION Autosomal recessive
LAB High blood levels of leucine, isoleucine, alloleucine, alloisoleucine, valine and corresponding ketoacids during acute attacks
ENZYME Branched-chain keto acid decarboxylase (deficient)
SUBSTRATE (a) ï¡-Ketoisovalerate
(b) ï¡-Keto-ï¢-Methylvalerate
PATHWAY Amino acid metabolism (Isoleucine-Valine biosynthetic pathway)
CLINICAL Overwhelming acidosis, vomiting and CNS symptoms, mental retardation and respiratory failure (infrequent), may be fatal
TREATMENT Dietary restriction of leucine, isoleucine and valine
of 58
Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Homocystinuria
INCIDENCE 1 / 200,000
GENETICS Cystathionine synthetase mapped to human chromosome 21q22
TRANSMISSION Autosomal recessive
LAB High urine levels of homocystine, methioinine and its sulphoxide. Elevated levels of homocystine and methionine also found in blood
ENZYME Cystathionine ï¢-synthetase
SUBSTRATE Homocysteine
PATHWAY Amino acid metabolism
CLINICAL Ocular, skeletal and vascular defects. Patients exhibit Osteoporosis and Marfan like appearances. Mental retardation, venous and arterial thrombosis
TREATMENT Pyridoxine, low methionine diet supplemented with cystine
of 58
Metabolic disorder
Genetics FlashCard? FlashMode: Off Term Description
Histidinemia
INCIDENCE 1 / 20,000
GENETICS Defective enzyme mapped to chromosome 12q22-q23
TRANSMISSION Autosomal recessive
LAB Elevated blood levels of histidine and alanine.
Excess urine levels of imidazole, pyruvic acid and other histidine metabolites
ENZYME Histidase (deficient)
SUBSTRATE Histidine
PATHWAY Amino acid metabolism
CLINICAL Mental retardation or speech defects common
TREATMENT Dietary restriction of histidine
of 58
Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Fabry disease
TRANSMISSION X-linked recessive
LAB Accumulation of trihexosylceramide and digalactosylceramide in body tissues
ENZYME Trihexosylceramide ï¡-glycosidase (deficient)
SUBSTRATE Galactosylgalactosyl-glucosyl ceramide (Gal-Gal-Glc-Cer)
PATHWAY Glycolipid metabolism
CLINICAL Hemizygous males have skin lesions, opacity of the eye, periodic fevers, burning sensation and pain in lower extremities, angiokeratoma on buttocks and around navel, edema due to kidney malfunction. Heterozygous females have much milder symptoms. Frequently leads to kidney and heart failure.
TREATMENT Renal transplantation has been employed as a rational mode of intervention. Attempts have also been made to correct the condition by retroviral vectors with ï¡-glycosidase A expression
of 58
Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Phenylketonuria
INCIDENCE 1/10,000
GENETICS Mapped to human chromosome 12q24.1
TRANSMISSION Autosomal recessive
GENE PAH gene
LAB High blood and urine levels of phenylalanine
ENZYME Phenylalanine hydroxylase (deficient)
SUBSTRATE L-Phenylalanine
PATHWAY Amino acid metabolism
CLINICAL Mental retardation, seizures, eczema
TREATMENT Dietary restriction of phenylalanine at an early stage of the disease can prevent the occurrence of mental retardation
of 58
Metabolic disorder Genetics FlashCard? FlashMode: Off Term Description
Tay-Sachs disease
INCIDENCE More prevalent in Ashkenazi Jews (1/2500 to 1/5000). In general its frequency of occurrence is 1/1,000,000
GENETICS Hexosaminidase A gene mapped to chromosome 15q 23-q24
TRANSMISSION Autosomal recessive
ENZYME Hexosaminidase A (deficient)
SUBSTRATE N-acetylneuraminic acid (NANA)
PATHWAY Glycolipid metabolism
CLINICAL Mental retardation, blindness, cherry red macula, muscular weakness, seizures, fatal
NOTES Also known as Type I GM2 - gangliosidosis. Sandoff disease is Type II GM2 gangliosidosis
of 58