DISORDER PATHOPHYSIOLOGY CLINICAL FEATURES TREATMENT

Galactosemia - abnormal  Galactose-1-phosphate uridyltransferase 1 vomiting, Exclusion of galactose from the diet
CARBOHYDRA

accumulation of galactose in body (GALT) diarrhea,

organ systems  Galactokinase (GALK) failure to thrive, lactose containing milk and food are substituted with
TE

 UPD galactose-4-epimerase (GALE) hepatomegaly, casein hydrolysates and soy milk

splenomegaly,
neonatal jaundice
cataracts (2/2 galactitol accumulation)
Classic organic acidurias - deficiency Accumulation of toxic intermediates sudden onset of encephalopathy and episodic Dietary restrictions of relevant amino acids and
PROTEI

of enzymes in the mitochondrial Disturbance of mitochondrial energy metabolic acidosis avoidance of protein catabolism
metabolism of coenzyme A-activated metabolism and carnitine homeostasis
N

carboxylic acid Supplementation with carnitine and glycine (adjuncts)

Phenylketonuria - phenylalanine is deficiency in the activity of phenylalanine Mentally retarded  Intellectual disability Dietary restriction of phenylalanine intake
AROMATIC AMINO ACIDS

metabolized to the phenyl ketones that
are excreted in the urine
Autosomal recessive
Other d/o:
 Tyrosinemia
 Alkaptonuria
 Albinism
 Hawkinsinuria
Maple Syrup Urine Disease (MSUD) -
passage of urine that has a
sweet, maple syrup-like odor
BRANCHED CHAIN AMINO ACIDS
hydroxylase - catalyzes the conversion of Stunted
phenylalanine to tyrosine. light skinned Continuous Phenylalanine restricted diet
Eczematoid rash or intractable itching
“musty” or “mousey” smelling individual (2/2 to Modification of phenotypic expression of defective
phenylacetate) gene
microcephaly
enamel hypoplasia Definitive: correcting the gene defect
hyperactivity with autistic behaviors
seizures
tremors
athetosis
hyperreflexia
Accumulation of 3 branched chain ketoacids Sudden onset lethargy Inhibit endogenous protein catabolism, sustain protein
 Alpha ketoisocaproic acid high-pitched crying, synthesis, prevent deficiency of essential amino acids,
 Alpha ketoisovaleric acid feeds poorly, and maintaining normal serum osmolality
becomes opisthotonic, and comatose

 Alpha keto B methylvaleric acid

5 phenotypes of MSUD Seizure Peritoneal dialysis and hemodialysis
 Classic Accumulation of BCAA and 2-hydroxy acids in hypoglycemia
 Intermittent the plasma, urine, and CSF Encephalopathy because of cerebral edema Special diets (MSUD powder) and strict protein
 Intermediate - Accumulation is a consequence of a spastic restriction
 Thiamine-responsive defect in oxidative decarboxylation of intellectually- retarded
 E3 deficient branched chain ketoacids
Methylmalonic acidemia Defect methylmalonyl CoA mutase Neonatal ketoacidosis Correction of acidosis and prevention of further
Lethargy catabolism
Vomiting
profound hypotonia, Restriction of isoleucine, methionine, valine, and
profound metabolic acidosis threonine (medical food available)
Hema findings:
Anemia Trail of Vit B12
Leukopenia
thrombocytopenia Growth hormone tried in suboptimal growth
 Isovaleric acidemia Isovaleryl CoA dehydrogenase deficiency Stale perspiration, sweaty feat, or ripe cheese Low protein

First week: acidosis, coma L-carnitine

Chronic: lethargy, vomiting, ataxia, and Glycine

ketoacidosis
Glutaric aciduria - Resemble Hypotonia, dystonia, choreoathetosis, and seizure High calorie, low protein diet, carnitine
extrapyramidal cerebral palsy
Macrocephaly, loss of appetite, profuse sweating Give carnitine as supplement
Diagnosis: and hypoglycemia, sleeplessness
 Neuroimaging: batwing
appearance (frontotemporal
atrophy)
 Caudate atrophy
 Bilateral subdural hematoma
Urea Cycle Enzyme Carbamoyl palmytoyl synthese difiiency (CPS) Progressive lethargy, apnea and or seizures Removal of ammonia by peritoneal dialysis or
UREA CYCLE
ENZYME D/O

Ornithine transcarbamoylase deficiency (OTC) Hyperammonemia without metabolic acidosis hemodialysis

Argininosuccinate synthetase deficiency Unexplained vomiting, intermittent headaches,
(Citrullinemia) behavioral changes, or acute encephalopathy
Argininosuccinase deficiency (Argininosuccinic
aciduria)
Ornithinemia
Homocystinuria - Arteriovenous seizures, developmental slowing or cerebrovascular Pyridoxine (100-500 mg/day)
SULFUR-CONTAINING AA

thromboembolism – common cause of accident occur between 5-9 months, regression of

death developmental milestones. Dietary restriction of methionine

Hair is sparse, blond and brittle and multiple Folate (1-15 mg/ day)
Cystathionuria erythematous blotches are seen in the cheeks
Mercaptolactate-cysteine disulfiduria Betaine
Sulfite oxidase deficiency subluxed lens, glaucoma, cataracts, and optic
atrophy Aspirin and dipyridamole

osteoporosis, pectus excavatum, “Marfan-like”

habitus
Fatty Acid Oxidation Hepatic presentation - Hypoketotic, hypoglycemia, Treat it early
hyperammonemia, elevations of serum urea, uric
acid, and liver enzymes Prevent hypoglycemia during infancy

Cardiac - Progressive heart failure between 2-3 Frequent feeding

FAO D/O

years old
Cardiomyopathy is accompanied by acute hepatic
syndrome

Muscles - sudden muscle weakness associated with

myoglobinuria and renal failure during strenuous
exercise