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