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MG10 Medical Genetics
References
Toronto Notes 2019
Table 8. Other Metabolic Disorders
Metabolic disease must be ruled out in any newborn who becomes acutely ill after a period of normal behaviour and development or with a family history of early infant death even if the newborn screen is negative
Epidemiology Etiology
Clinical Presentation
Diagnosis and Management
Phenylketonuria
1:10,000; autosomal recessive disease (mutations in PAH)
Deficiency of phenylalanine hydroxylase prevents conversion of phenylalanine to tyrosine leading to build- up of toxic metabolites
Mothers who have PKU may have infants with congenital abnormalities
Baby is normal at birth, then develops a musty odour, eczema, hypertonia, tremors and mental retardation
Hypopigmentation due to low tyrosine (fair hair, blue eyes)
PKU screening at birth
Dietary restriction of phenylalanine starting within the first 10 d of life; especially important during pregnancy to maintain normal phenylalanine levels to prevent maternal PKU effects on fetus
Large neutral amino acid (tyrosine) replacement, BH4 enzyme treatment, phenylalanine lyase treatment are other options
Galactosemia
1:60,000; autosomal recessive disease
Most commonly due to deficiency of galactose-1- phosphate uridyltransferase leading to an inability to process lactose/galactose
Signs of liver and renal failure, jaundice, FTT, and cataracts with ingestion of lactose/ galactose
Complications:
Increased risk of sepsis, especially E. coli
If the diagnosis is not made at birth, liver and brain damage may become irreversible
Elimination of galactose from the diet (e.g. dairy, breast milk) Most infants are fed a soy-based diet
Maple Syrup Urine Disease
1:185,000; autosomal recessive disease (mutations in BCKDHA, BCKDHB, and DBT genes)
Reduction or elimination of protein complex needed for amino acid leucine, isoleucine and valine breakdown, leading to toxic build-up
Feeding intolerance, failure to thrive, vomiting, lethargy, and maple syrup odor in urine and cerumen
May progress to irreversible mental retardation, hyperactivity, severe failure to thrive, seizures, coma, cerebral edema, and death if inadequately treated
Serum amino acid evaluation (leucine, isoleucine, alloleucine, valine) and urine organic acid analysis
Protein-restricted, high- carbohydrate diet to limit branched amino acid intake
A trial of thiamine therapy in addition may be recommended for some infants
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