Metabolic Disorders

Question 1

12 to 24 hours of age, the mother noted a sweet, caramel-like odor. 2 days of age, the newborn was feeding poorly, becoming irritable, and then developed drowsiness that progressed to lethargy, intermittent apnea, opisthotonus, and hypertonia. “bicycling” movements of the legs.

Answer 1

maple syrup urine disease (MSUD)

Question 2

Things that build up in blood with Maple Syrup urine disease

Answer 2

amino acid levels

Question 3

Inheritance pattern of MSUD

Answer 3

autosomal recessive

Question 4

Clinical features of Menkes disease

Answer 4

a period of normal development in early infancy, followed by developmental regression, coarse, kinky hair (pili torti), and tortuosity of the carotid arteries and vasculature of the brain.

Question 5

Things to test to diagnose Menkes Disease

Answer 5

Ceruloplasmin levels, in conjunction with copper levels

Question 6

Dx for Mucopolysaccharidoses

Answer 6

lysosomal enzyme screening and urine glycosaminoglycans

Question 7

Clinical features of mucopolysaccharidoses

Answer 7

slowly progressive coarsening of facial features, joint stiffness, and developmental regression.

Question 8

Diagnostic lab test for peroxisomal disorders,

Answer 8

Very-long-chain fatty acids

Question 9

Clinical features of peroxisomal disorders

Answer 9

slow progression of hypotonia, poor feeding, dysmorphic facies, seizures, hepatic dysfunction, retinal dystrophy, and sensorineural hearing loss

Question 10

Lab abnormalities in medium-chain-acyl-coenzyme A dehydrogenase (MCAD) deficiency

Answer 10

Elevations in C6, C8, and C10 acylcarnitines

Question 11

Things included in newborn screen (just major ones among the full 30)

Answer 11

PKU, galactosemia, organic acidemias, fatty acid oxidation disorders, congenital adrenal hyperplasia, congenital hypothyroidism, and sickle cell disease

Question 12

Presentation and timing of medium-chain-acyl coenzyme A dehydrogenase (MCAD) deficiency

Answer 12

3 and 24 months of age with an episode of hypoketotic hypoglycemia, vomiting, and lethargy triggered by a minor illness

Question 13

Clinical presentation of Propionic acidemia

Answer 13

developmental regression, frequent emesis, protein intolerance, failure to thrive, low tone, dystonia, and cardiomyopathy.

Question 14

Lab findings in proprionic acidemia

Answer 14

elevated C3 (propionylcarnitine) AND elevated urine organic acids (3-hydroxypropionate level and the presence of methylcitrate, tiglylglycine, and priopionylglycine)

Other miscellaneous: metabolic acidosis with a high anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias

Question 15

Baby has virilization, salt-wasting crisis. You suspect ____ and you test for _____

Answer 15

Congenital adrenal hyperplasia (CAH)
17-OH progesterone level

Question 16

child presenting with developmental regression, ECZEMA, hypotonia, ataxia, vision problems, hearing loss, ALOPECIA, and seizures. What does he/she have and what do you test for.

Answer 16

Biotinidase deficiency
biotinidase level

Question 17

Basic metabolic workup include (10 things)

Answer 17

1. serum analysis for lactate,
2. pyruvate,
3. ammonia,
4. blood glucose,
5. complete blood count,
6. electrolytes,
7. carnitine profile,
8. acylcarnitine panel, and
9. amino acids, as well as
10. UA for organic acids and ketones

Question 18

What is the issue in Phenylketonuria (PKU)

Answer 18

excess serum phenylalanine
amino acid metabolism

Impaired myelination –> profound neurologic impairment

Question 19

Dietary change in children with PKU

Answer 19

natural proteins supplemented with phenylalanine-free amino acid mixtures

Question 20

coarse facial features, macrocephaly, contractures of the hands, a gibbus deformity, and corneal clouding. Normal features at birth. Multiple episodes of otitis media. Development delay. Short stature. Dx?

Answer 20

Hurler syndrome

Question 21

Deficiency of the enzyme α-L-iduronidase leads to storage of 2 glycosaminoglycans (GAGs), dermatan and heparan sulfate, in various tissues and organs

Answer 21

Hurler

Question 22

Tx of Hurler and when they should it be given by

Answer 22

HSCT (does not help with cardiorespiratory issues l
By 30 mo

In MPS1, enzyme replacement therapy
Does not cross BBB so does not help with cognitive decline

Question 23

x-linked lysosomal storage disorder characterized by periodic pain crises, angiokeratomas, corneal and lenticular opacities, stroke, left ventricular hypertrophy, sweating abnormalities, and renal disorder progressing to end-stage renal disease

Answer 23

Fabry

Question 24

Hunter syndrome pathophys

Answer 24

accumulation of the GAGs dermatan and heparan sulfate due to a deficiency of the enzyme iduronate sulfatase

Question 25

Hunter vs. Hurler

Answer 25

Hunter has better cognitive outcome and the absence of corneal clouding.

Question 26

lysosomal storage disorder caused by a deficiency of the enzyme acid α-glucosidase

Answer 26

Pompe

Question 27

proximal muscle weakness with respiratory insufficiency; there is no cardiac involvement

Answer 27

Pompe In pompe, the "pump" is fine

Question 28

Hypoketotic hypoglycemia with no urine ketones. Dx? What is the ammonia level?

Answer 28

Fatty acid oxidation problem Normal ammonia

Question 29

Which two inborn errors metabolism with hypoglycemia is hyperammonimea seen?

Answer 29

Urea cycle defects Organic acidosis (maple syrup)

Question 30

Types of urea cycle defects

Answer 30

ornithine transcarbamylase deficiency citrullinemia argininosuccinic aciduria

Question 31

Types of organic acidosis

Answer 31

isovaleric aciduria methylmalonic aciduria propionic aciduria maple syrup urine disease. The

Question 32

most common disorder of muscle glycogenosis with primary clinical feature of exercise intolerance, presenting with fatigue, pain, and cramps in the exercising muscle.

Answer 32

Glycogen storage disease V (McArdle)

Question 33

Glycogen storage disease type 2 is also known as

Answer 33

Pompe disease

Question 34

Exercise intolerance with second wind phenomenon. Dx?

Answer 34

McArdle Glycogen storage disorder type V

Question 35

Pancytopenia Erlenmeyer flask deformity of bones (femur) with bone pain Hepatosplenomegaly. Dx?

Answer 35

Gaucher

Question 36

Pathophys of Gaucher disease

Answer 36

disorder of sphingolipid metabolism

Question 37

calcification of the mitral and aortic valves, mild splenomegaly, corneal opacities, and oculomotor apraxia.

Answer 37

Cardiovascular Gaucher

Question 38

Binge marrow biopsy findings of Gaucher

Answer 38

Large vacuolated macrophages

Question 39

obtundation after prolonged overnight fasting and hypoglycemia with lactic acidosis and ketosis, with hepatosplenomegaly, found in infancy. Dx?

Answer 39

Glycogen storage disorder type 1a (von Gierke disease)

Question 40

Deficiency/defect in glucose-6-phosphatase. Dx?

Answer 40

Glycogen storage disorder type 1A

Question 41

ragged red fibers (also other non-specifoc findings like seizure, hypotonia, cardiac conduction abnormalities)

Answer 41

Mitochondrial disorder

Question 42

Newborn screen with positive trypsinogen (concerning for CF). Next steps?

Answer 42

Schedule for diagnostic testing elevated trypsinogen could show pancreatic insufficiency in newborns with CF

Question 43

Target glucose for neonate

Answer 43

>45 (AAP) Pediatric endocrine society: >50 in first 48h, then >60 after

Question 44

If neonate has glucose of <35, what is the next step?

Answer 44

Feed and remeasure 1h after feed. If still <35, then IV glucose

Question 45

When does physiologic hypoglycemia occur

Answer 45

First 4 hours of life

Question 46

Difference between urea cycle defect and organic acid defect

Answer 46

Urea cycle defect: respiratory alkalosis Organic acid defect: metabolic acidosis, BUN wnl

Question 46

Difference between urea cycle defect and organic acid defect

Answer 46

Urea cycle defect: respiratory alkalosis, normal AG Organic acid defect: metabolic acidosis, BUN wnl

Question 47

Tx of urea cycle defect

Answer 47

low-protein diet essential amino acid and arginine supplement Nitrogen scavenger meds: sodium phenylacetate and sodium phenylbutyrate

Question 48

Boy with dystonia, choreoathetosis, spasticity, low tone and global developmental delay wince 3 mo. Dx with CP at 2 yo. Frequent self-injurious behaviors. Nondysmorphic. Family history + for similar. What's the diagnosis and what do you send off?

Answer 48

Lesch-Nyhan Commonly mistaken as CP Urinary urate-to-creatinine ratio (>2.0 in LN)

Question 49

Lesch-Nyhan pathophys

Answer 49

uric acid overproduction leading to deposition of uric acid crystals in bladder, kidneys, ureters over time

Question 50

Orange crystals in diaper, dx?

Answer 50

uric acid overproduction seen in Lesch-Nyhan

Question 51

Most common cause of inherited intellectual disability

Answer 51

Fragile X-syndrome

Question 52

extremely elevated ammonia, poor feeding, hypotonia, cerebral edema, respiratory alkalosis. dx?

Answer 52

urea cycle disorder

Question 53

difference between ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase I (CPS I) deficiency

Answer 53

in OTC deficiency, HIGH urine ortic acid

Question 54

mode of inheritance of OTC deficiency

Answer 54

X-linked recessive

Question 55

Tx of OTC crisis (severe hyperammonemia)

Answer 55

dialysis

Question 56

Tx of OTC crisis (severe hyperammonemia)

Answer 56

dialysis

Question 57

Tx of maple syrup urine disease

Answer 57

Dietary leucine restriction Supplementation with isoleucine and valine

Question 58

musty body odor, dx?

Answer 58

Phenylketonuria

Question 59

Hypotonia, poor feeding, dysmorphic facies, LIVER CYSTS with liver dysfunction, bony stippling in patella or long bones

Answer 59

Zellweger (peroxisomal biogenesis disorder, elevated very-long fatty acid in serum)

Question 60

What does MELAS stand for

Answer 60

mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes

Question 61

DOwnward dislocation of the lens

Answer 61

homocysteinuria

Question 61

DOwnward dislocation of the lens

Answer 61

homocysteinuria

Question 62

Elevated C14:1 on newborn screen

Answer 62

very long-chain acyl-coA dehydrogenase (VLCAD) deficiency

Question 63

cardiomyopathy with pericardial effusion (or hyperkeratotic), hepatomegaly, hypotonia, elevated AST/ALT, increased dicarboxylic acids. serum elevated dicarboxylic acids. Dx?

Answer 63

VLCAD, very long-chain acyl-coA dehydrogenase deficiency

Question 64

Barth sd

Answer 64

mitochondrial dz. TAZ mutation cardiomyopathy, muscular weakness Neutropenia ** (unlike VLCAD) Facial dysmorphology elevated urine 3-methylglutacomic acid, 3-methylglutaric acid, 2-ethylhydracylic acid

Question 64

Barth sd

Answer 64

mitochondrial dz. TAZ mutation cardiomyopathy, muscular weakness Neutropenia ** (unlike VLCAD) Facial dysmorphology elevated urine 3-methylglutacomic acid, 3-methylglutaric acid, 2-ethylhydracylic acid