Page 667 - TNFlipTest

Toronto Notes 2019 Syndromes and Diseases Medical Genetics MG9 Metabolic Diseases
• inheriteddisordersofmetabolism;most,butnotall,areautosomalrecessive
• infantsandolderchildrenmaypresentwithfailuretothriveordevelopmentaldelay
• organelle disorders can present with dysmorphism
• universalnewbornscreeninginOntarioincludestreatablemetabolicdisorders
Table 7. Metabolic Disorders
Examples of Conditions
Clinical Manifestations
Laboratory Findings
Physical Exam
Organic and Amino Acid Disorders
PKU
Tyrosinemia Homocystinuria MSUD Alkaptonuria
Urea cycle defects
Irritability, lethargy, poor feeding
Seizures
Intellectual disability Vomiting and acidosis after feeding initiation Sweet-smelling urine (MSUD)
Hypoglycemic hyperammonemia, high anion gap (organic acidemia) Normoglycemic hyperammonemia, normal anion gap (urea cycle defects)
Hypotonia/hypertonia Microcephaly, musty odour, eczema, hypopigmentation (PKU) Dark urine, pigmented sclerae, arthralgias (alkaptonuria)
Lens subluxation, marfanoid appearance (homocystinuria)
Carbohydrate Disorders
Galactosemia Glycogen storage diseases (GSDs): von Gierke’s, Pompe’s, Cori’s, Andersen, McArdle
Hepatomegaly, liver failure Hypoglycemia Growth retardation, failure to thrive
Elevated liver enzymes (Galactosemia) Hypoglycemia,
lactic acidosis, hyperlipidemia (GSD)
Infantile cataracts (galactosemia) Hepatomegaly Muscle weakness/ cramping
Fatty Acid Disorders
MCAD deficiency VLCAD deficiency LCHAD deficiency
Lethargy, poor feeding Seizures, coma Symptoms triggered by fasting
Liver dysfunction Sudden infant death
Hypoketotic hypoglycemia
Elevated free fatty acids
Hepatomegaly Hypotonia
Organelle Disorders
Congenital disorders of glycosylation
Lysosomal storage diseases: Hunter's, Hurler’s, Niemann- Pick, Tay-Sachs, Gaucher, Fabry, Krabbe
Peroxisomal defects: Zellweger syndrome, X linked adrenoleukodystropnhy
Progressive neurological problems
Chronic encephalopathy Developmental delay Bone crises (Gaucher) Deafness, blindness
Elevated urine oligosaccharides, (oligosaccharidoses)
and glycosaminoglycans (mucopolysaccharidoses), abnormal transferrin isoelectric focusing (congenital disorders of glycosylation), abnormal very long chain fatty acids (peroxisomal defects)
Dysmorphic facial features Macrocephaly (Tay-Sachs, Hurler’s)
Hepatosplenomegaly (Niemann- Pick type A/B/C, not Tay-Sachs) Cherry-red spot on macula (Niemann-Pick type A/B, Tay- Sachs, Gaucher’s)
Corneal clouding (Hurler’s) Infantile cataract (Fabry) Peripheral neuropathy (Fabry, Krabbe)
Spasticity
Initial Investigations for a Child with Acute Problems thought to be
Due to an Inborn Error of Metabolism
• importanttosendlabstudiesatinitialpresentationinordertofacilitateimmediatediagnosisand
treatment
• checknewbornscreeningresults
• electrolytes,ABGs(calculateaniongap,ruleoutacidosis)
• CBCwithdifferentialandsmear
• bloodglucose(hypoglycemiaseenwithorganicacidemia,fattyacidoxidationdefects,andGSDs)
• lactate, ammonium (hyperammonemia with urea cycle defects or organic acidemias), plasma Ca2+ and
Mg2+
• routineurinalysis:ketonuriamustbeinvestigated
• carnitinelevelswithacylcarnitineprofile
• others:urate,urinenitroprusside,plasmaaminoacidscreen,urineorganicacids,CSFglycine,freefatty
acids (3-β-hydroxybutyrate ratio >4 in fatty acid oxidation defect)
Treatment
• variesaccordingtoinbornerrorofmetabolism