Occurrence of lipofuscin in inherited metabolic disorders ...
Metabolic and Inherited Disorders
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Transcript of Metabolic and Inherited Disorders
Metabolic/Inherited Disorders
I. Definition Metabolic disorders or inborn errors of metabolism are hereditary “autosomal recessive traits” and are caused by the absence or reduced enzyme or cofactor activity
II. Management A. Newborn screening -most inherited metabolic disorders are associated with severe clinical illness that appears soon after birth Blood test taken from a baby on the third day of life to identify those that are born with metabolic/inherited problems. An early identification is important to avoid irreversible mental retardation or death. In most developed countries (i.e., USA, Japan, Australia), newborn screening is offered as a routine public health measure. In the Philippines, it is now available in some hospitals
B. Newborn screening tests for six metabolic/inherited disorders
1. Congenital hypothyroidism 2. Phenylketonuria 3. Congenital adrenal dyperplasia 4. Galactosemia 5. Homocystonuria 6. Maple syrup urine disease
C. Methods of Nutritional Management 1. Restriction of substrate 2. Supplementation of product 3. Supplementation of enzyme or cofactor 4. Combination of any or all of the methods
III. Nutritional Care
To maintain biochemical equilibrium for the affected pathway, provide adequate nutrients to support normal growth and development, and support social and emotional development
IV. Assessment of Treatment
A. Regular monitoring of weight and growth pattern B. Regular monitoring and evaluation of food diary C. Careful and frequent monitoring of pertinent laboratory tests D. Diet modifications are adjusted according to the above-mentioned factors E. Continuous nutrition education to the family
V. Summary of some metabolic/inherited problems
Disorder Defective Enzyme Characteristics Diet
Amino Acids 1. Maple syrup urine
disease
2. Phenylketonuria
α-keto-decarboxylase Phenylalanine hydroxylase
Increased blood concentration of BCAA leucine, isoleucine, and valine Progressive severe MR, prevented by early treatment Increased blood concentration of phenylalanine; increased urine level of phenylpyruvic acid and phenylacetic acid; MR
BCAA-free fomula (MSUD powder, analog MSUD) Low phenylalanine diet Low phenylalanine (Lofenalac) or phemylfree formula (Phenyl Free,
Disorder Defective Enzyme Characteristics Diet
3. Homocystinuria
4. Tyrosinosis
Cystathionine synthase p-hydroxy-phenylpyruvic acid
Increased methionine, increased homocystine; arterial & venous thrombosis, bony abnormalities, dislocated lens, mild to moderate MR
Maxamaid, Analog, X-Phen, PKU-1, PKU-2); avoid aspartame Low protein; low methionine diet with added L-cystine Low phenylalanine and tyrosine
Urea Cycle Disorders 1. Carbamyl
phosphate synthetase defect
2. Ornithine trans-
carbamylase deficiency
3. Citrullinemia
4. Arginosuccinic aciduria
Carbamyl phosphate synthetase Ornithine transcarbamylase (X-linked) Arginosuccinic acid synthetase Argino-succinidase
Increased plasma ammonia, glutamine; vomiting, seizures, coma, death, MR Increased plasma ammonia, glutamine, glutamic acid, alanine; vomiting, seizures, coma, death Increased plasma citrulline, ammonia, alanine; vomiting, seizures, coma, death, progressive developmental delay Increased plasma arginosuccininc acid, citrulline, ammonia, hypotonia, seizures, vomiting, FTT, progressive developmental delay
Low protein, keto-acid mixture, sodium benzoate; hemo- or peritoneal dialysis Low protein and sodium benzoate Low protein, arginine, supplements, sodium benzoate Low protein, arginine supplement, sodium benzoate; dialysis
Organic Acidemias 1. Methylmalonic
aciduria (acidemia)
2. Propionic acidemia
Methylmalonyl CoA or coenzyme B12 Propionyl CoA carboxylase
Increased organic acids, ammonia, metabolic acidosis, vomiting, seizures, coma, often death, progressive, developmental delays in survival Increased ammonia, propionic acid in blood, metabolic acidosis, increased methylcitric acid in urine
Low isoleucine, threonine, valine and methionine; vitamin B12 1 mg/day IM High kilocalories, low protein, IV fluid, bicarbonate
Carbohydrates 1. Galactosemia
Galactose I-phosphate uridyl transferase
Increased urine and blood galactose; vomiting, hepatomegaly, hypoglycaemia, FTT, cataracts, MR, early
Galactose & lactose-free; special formulas may be used for infant feeding
Disorder Defective Enzyme Characteristics Diet
2. Hereditary galactokinase
3. Fructose 1,6-diphosphate deficiency
Galactokinase Fructose 1,6-diphosphatase
sepsis Increased blood, urine galactose after feeding with lactose, cataracts Hypoglycemia, hepatomegaly, hypotonia, metabolic acidosis, on fructose introduction
Galactose and lactose-free Fructose-, sucrose- and sorbitol-free
Glycogen Diseases 1. Type O-glycogen
synthetase deficiency
2. Type I: glucose 6-P defect (Van Creveld-Von Gierke’s Disease)
3. Type IIB: α-1,4-
glucosidase defect (acid maltase deficiency)
4. Type III:
debranching enzyme defect (limit detrinosis or Forbes disease)
5. Type IV: reduced hepatic phosphorylase activity
6. Type V: branching
enzyme defect (Her’s disease)
Absence of glycogen synthetase Glucose-6-phosphatase α-1,4-glucosidase Amylo-1,6-glucosidase defect Hepatic phosphorylase α-1,4 glycan 6-glycosyl transferase
Liver has very low glycogen content Hypoglycemia, hyperlipidemia, hepatomegaly, growth retardation, osteoporosis, metabolic acidosis Muscle weakness, hypotonia Hepatomegaly, growth failure, hyperlipidemia, fasting hypoglycaemia Heptaomegaly, mild to moderate, growth failure, hyperlipidemia, fasting hypoglycaemia Hepatic deterioration, FTT, cirrhosis, portal hypertension, ascites, esophageal varices
High protein, frequent carbohydrate feeding, extra meal at night Frequent feeding with raw corn starch, high carbohydrate, limited in lactose & fructose, low fat High protein High protein, limited sugar free sugar, frequent feedings; total kilocaloric distribution: 25-25% protein 40-50% CHO 25-35% fat Nocturnal tube feedings of corn starch Nocturnal corn starch or high carbohydrate continuous enteral tube feeding Nocturnal tube feeding or oral corn starch feedings
VI. Other inherited/congenital problems
Disorder Characteristics Treatment
Congenital hypothyroidism *low or absent thyroid hormone *occurs in one of every 4,000 newborns *part or all of the thyroid gland failed to develop *enzyme needed to produce thyroid hormone is missing
Thyroid hormone pills
Disorder Characteristics Treatment
Congenital adrenal hyperplasia
*occurs in one of every 12,000 births *salt is lost in the urine *high levels of male hormones in both boys and girls
Early detection to avoid serious illness due to salt loss
Down’s Syndrome (Trisomy 21)
*associated with growth and mental retardation *poor suck and swallow during infancy, drooling *poor lip and tongue control *hypotonia *excessive weight gain/obesity *dental problems: delayed tooth development, periodontal disease, malocclusion, bruxism *compromised cardiac status
Feeding evaluation by qualified professional to develop appropriate feeding program
Tube feeding if needed Adjust texture of diet Use adaptive feeding technique; good
dental hygiene High kcal diet if weight gain is poor Monitor Na intake if cardiac status is
compromised