Inborn Errors Of Metabolism

Question 1

Metabolic acidosis + elevated NH3

Answer 1

Propionic acidemia
Methylmalonic acidemia
Fatty acid oxidation defects

Question 2

Metabolic acidosis + normal NH3

Answer 2

MSUD

Some organic acidemias

Question 3

Normal ABG + elevated NH3

Answer 3

Urea cycle defect

Question 4

Normal ABG + normal NH3

Answer 4

Aminoacidopathy
Galactosemia
Non-ketotic hyperglycemia

Question 5

Organic acidemias

Answer 5

Elevated NH3
Anion gap acidosis
Introduction of protein (first 2 days)
Ketonuria
Hypoglycemia

Decreased appetite, delayed milestones
Falling down
No physical abnormality

Question 6

Isovaleric acidemia

Answer 6

Lethargy
Poor feeding
Seizure
Infection
Odor of sweaty feet

Tx: protein restriction

Question 7

Propionic acidemia

Answer 7

Newborn period

Lethargy, poor feeding

Question 8

Methylmalonic acidemia

Answer 8

Newborn period

Lethargy, poor feeding

Question 9

Fatty acid oxidation defects

Answer 9

Autosomal recessive

MCAD, LCAD, VLCAD
Hypoglycemia
Hepatomegaly
Absence of reducing substances, ketones
Normal serum amino acids

Dx: plasma acylcarnitine profile

Question 10

Urea Cycle Defects

Answer 10

Hyperammonemia
No acidosis

Symptom free -> hypotonia, coma

Tx: protein restriction, IV glucose

Question 11

Galactosemia

Answer 11

After first meal
Abdominal distension
Hypoglycemia
Non-glucose reducing substances in urine
Gm negative sepsis
Cataracts (reversible), retardation, liver disease

Dx: GALT in RBCs
Tx: galactose free diet

Question 12

Fructose intolerance

Answer 12

Seizures after a meal

Question 13

Hyperinsulinism

Answer 13

Hypoglycemia

Ht, wt, HC upper limit of normal

Question 14

Refractory hypoglycemia

Answer 14

Diazoxide

Question 15

Biotinidase deficiency

Answer 15

Lactic acidosis
Itchy rash
Alopecia
Coma, ataxia, neuro signs

Tx: biotin supplements

Question 16

Maple Syrup Urine Disease

Answer 16

Onset in 1st week
Hypertonicity
Shallow breathing

Elevated AA:
valine, isoleucine, alloisoleucine, leucine

Question 17

Alcaptonuria

Answer 17

Homogentisic acid in urine -> dark diaper

Tx: low phenylalanine, tyrosine diet

Question 18

Homocystinuria

Answer 18

Dislocated lens
Skeletal abnormalities
Cognitive defects

Dx: homocysteine in urine
Tx: pridoxine; high cysteine, low methionine diet

Question 19

Phenylketonuria

Answer 19

Asymptomatic for few mos
Blond hair, blue eyes

Vomiting, irritability
Eczema
Mousy odor of urine

Microcephaly, low BW
Congenital heart disease
Mental retardation

Dx: after first feeding
Tx: continue diet, esp before pregnancy

Question 20

Mucopolysaccharidoses

Answer 20

Type I: Hurler

Type II: Hunter

Type III: Sanfilippo

• autosomal recessive
• increases haparan sulfate
• hepatosplentomegaly, corneal clouding

Type IV: Morquio

• skeletal involvement, corneal clouding
• normal IQ

Question 21

Glycogen storage disease type 1

Von Gierke disease

Answer 21

Consanguinity
Fasting (infant sleeping through night)

Hepatomegaly
Cherubic facies
Hypoglycemia
Elevated TG, cholesterol
Elevated lactic acid, uric acid

Tx: cornstarch, no fasting

Question 22

Glycogen storage disease type 2

Pompe disease

Answer 22

One month or younger
Hypotonia, FTT
Hepatomegaly
Macroglossia
Cardiomegaly

No hypoglycemia, acidosis

Question 23

Familial hypercholesterolemia

Answer 23

Autosomal dominant

Not associated with obesity

Question 24

Menkes syndrome

Answer 24

Autosomal recessive
Low serum Cu, ceruloplasmin
High tissue Cu level

Question 25

Wilson's disease

Answer 25

Jaundice, hepatomegaly Neurological deterioration Kayser Fleischer rings, no visual defects Dx: liver biopsy

Question 26

Gaucher disease

Answer 26

Decreased beta glucosidase activity 1st/2nd year, progressive Hepatosplenomegaly, CNS deterioration Short stature Thrombocytopeia Bone pain Osteosclerosis, bone lesions

Question 27

Fabry disease

Answer 27

``` X recessive Absence of alpha galactosidase Orange skin lesions (angiokeratomas) Burning of palms, soles Opacities of eye Vascular - kidney, heart, brain ```

Question 28

Krabbe disease

Answer 28

Demyelination disorder Progressive neuro deterioration Death by 2 yo

Question 29

Tay Sachs disease

Answer 29

Autosomal recessive Hexosaminidase A enzyme activity Normal development until 9 mos Progressive over 1st year, death by 4-5 yo Exaggerated startle reflex Cherry red spot on retina Macrocephaly

Question 30

Niemann Pick disease

Answer 30

Cherry red spot on retina CNS deterioration Hepatosplenomegaly

Question 31

Homocystinuria

Answer 31

``` Error in methionine metabolism Thin, scoliosis Posterior dislocated lens Cognitive impairment Risk for thrombi, emboli -> PE ``` Tx: pyridoxine

Question 32

Orithine transcarbamylase deficiency

Answer 32

``` X linked Urea cycle defect Hyperammonemia, low BUN Lethal at early age in males Increased glutamine, urinary orotic acid Decreased citrulline, argiine ```