Metabolics MCQ

Question 1

2-year-old boy with a known history of MCAD (medium-chain acyl-CoA dehydrogenase) deficiency presents with lethargy and vomiting, in the context of a 1-day history of fever and cough. On arrival, his blood glucose was 2.8mmol/L. What is the pathophysiology of his presentation? (This was the exact wording, they did not ask “what is the pathophysiology of his hypoglycemia”).

Impaired glycogenolysis
Impaired ketogenesis
Impaired carbohydrate metabolism
Decreased glycogen stores

Answer 1

impaired ketogenesis

MCAD patients present as hypoketotic due to an inability to break down medium chain fatty acids to use for GNG and ketone body formation
Not an issue of impaired glycogenolysis, impaired carbohydrate metabolism or decreased glycogen stores

Question 2

6-month-old male infant is referred to you for failure to thrive. Labs show Na 139, K 4, Cl 113, HCO3 16, pCO2 30, pH 7.31. What is the BEST interpretation of these results?

Metabolic acidosis with wide anion gap secondary to amino acid disorder
Metabolic acidosis with normal anion gap secondary to amino acid disorder
Metabolic acidosis with wide anion gap secondary to renal tubular acidosis
Metabolic acidosis with normal anion gap secondary to renal tubular acidosis

Answer 2

Metabolic acidosis with normal anion gap secondary to renal tubular acidosis

AG = 10 (normal)

Non-anion gap metabolic acidosis = renal or GI

Prox RTA = bicarb wasting (can have normal K)

thus renal

Question 3

13 yo male with 7 days of polyuria and weight loss. Has 24 hours of tachypnea. What is the metabolic mechanism of his presentation?

Increased glucose utilization by liver
Decreased liver glycogenesis
Decreased gluconeogenesis
Increased lipolysis

Answer 3

Increased lipolysis
this pt is in DKA
The body thinks it’s starving in dka because of the lack of insulin bringing glucose into cells. So lipids are broken down for energy

Question 4

2-day old female presenting with blood glucose of 1.6 mmol/L two and a half hours after a feed, also found to have hepatomegaly. What is most consistent with her underlying condition?
Negative ketones and abnormal acyl carnitine profile
Elevated lactate and uric acid
Decrease fatty acid and decrease ketones
Decrease lactate and elevated ketones

Answer 4

Elevated lactate and uric acid

Glycogen storage disorders have hepatomegaly (from glycogen building up), hypoglycemia

Question 5

3 year old child with splenomegaly (confirmed on US) since 18 moths of age, normal development apart from gross motor and clumsy. Parents describe she prefers to be carried. She has recurrent viral illness and each time, has low platelets but otherwise normal labs. What is the most likely diagnosis?
Recurrent viral illness
Glycogenic storage disease -
Ebstein Bar Virus
Gaucher Disease

Answer 5

Gaucher Disease (lysosomal storage disease) - pancytopenia, bone pain, splenomegaly

Question 6

5 year old boy with lethargy associated with being ill. Labs show hypoglycemia around 2.1 with urinary ketones. Lytes, liver enzymes, all normal. Child has had previous episodes of mild lethargy with illnesses this year. What do you recommend

Avoid fasting and pay attention to nutrition during illness forever
Avoid fasting and pay attention to nutrition during illness until 8-9 years old
Glucagon during hypoglycemia
Hydrocortisone during illnesses

Answer 6

Avoid fasting and pay attention to nutrition during illness until 8-9 years old

Idiopathic Ketotic Hypoglycemia

Question 7

Baby born and found to have a positive PKU screen, what do you do next?
Immediately restrict phenylalanine from diet
Check serum phenylalanine level
Start medication therapy for PKU
Urine ketones

Answer 7

check serum Pku level to confirm the diagnosis

Question 8

5-month-old, previously healthy boy has 48 hours of URTI symptoms, fever and poor feeding. There is no hepatomegaly. His glucose level is 0.8, mild metabolic acidosis, elevated AST and ALT. There is no urinary ketones. IM glucagon was given and only improved glucose to 1.2. What is the most likely diagnosis?

Hyperinsulinism
Hypopituitarism
Glycogen storage disease
Fatty acid oxidation defect

Answer 8

fatty acid oxidation defect

Question 9

Metabolic acidosis after fasting with URTI. No ketones. Hypoglycaemia. Mildly raised LFTS.

1. FAOD
2. Mitochondrial
3. Hyperinsulinism

Answer 9

Fatty acid oxidation defect

Question 10

2 week old baby’s newborn screen came back positive for Carnitine Palmitoyltransferase II Deficiency. What is the best course of action until results are confirmed?
A. Start PO Carnitine
B. Feed frequently (Q3H)
C. Amino Acid formula
D. Hypercalori formula

Answer 10

Feed frequently

Primary Carnitine Deficiency is the only carnitine cycle defect where you treat by supplementing carnitine
The other defects are treated by avoiding fasting

Question 11

Fatty Acid Oxidation Defect. What is the most common presentation

a) Intractable Seizures
b) Coma

Answer 11

?coma

acute encephalopathy with hypoketotic hypoglycemia

Question 12

4 day-old male presents with E.coli sepsis and a midline abdominal mass. Which investigation is most likely to confirm dx?
a. AUS
b. VCUG
c. GALT level

Answer 12

Abdo US

Question 13

newborn presents with the following lab values pH 7.1; HCO3 decreased, normal sodium/potassium Elevated lactate, ammonia and neutropenia. Diagnosis:
a. galactosemia
b. MCAD
c. methamelonic acidemia - profound acidosis
d. urea cycle defect

Answer 13

methamelonic acidemia - profound acidosis

Question 14

Baby who presents to ED looking unwell with emesis, and lethargy. After fluid resuscitation, he improves. While in hospital, cow’s milk was re-introduced. Day 5 of his admission, he suddenly looks lethargic. Findings pH 7.1, HCO3=6, Na/K normal. High lactate, ammonia

a. galactosemia
b. methylmalonic acidemia
c. UCD

Question 15

2 year old boy 3 days of vomiting and diarrhea. Lethargic. Glucose low (2.4?). Ketones 2+. Most likely diagnosis?

fatty acid oxidation
glycogen storage
adrenal insufficiency
ketotic hypoglycemia

Answer 15

ketotic hypoglycemia

most likely idiopathic ketotic hypoglycemia

Question 16

2yo with 1 day of vomiting and diarrhea in the ER is lethargic. Blood glucose 2.0. Gets better after IV glucose. What will support your diagnosis?

A. Low GH
B. hyperinsulinism
C. urine for reducing substances
D. elevated urine ketones

Answer 16

elevated urine ketones

Question 17

5 month old boy who has been unwell for 48 hours (not feeding, lethargic) presents with glucose 0.8, metabolic acidosis, no urine ketones. Glucagon is given and raises the blood sugar to 1.2. What is the most likely diagnosis?

Glycogen storage disease
Fatty acid oxidation disorder
Hyperinsulinism

Answer 17

Fatty acid oxidation disorder

Question 18

in general, what is the typical inheritance pattern of metabolic disorders?

Answer 18

autosomal recessive

Question 19

what are small molecule inborn errors of metabolism?

Answer 19

Protein, Carb and Lipid disorders

Question 20

how do small molecule IEM present?

Answer 20

acutely
- often show up really sick in the ED.
-They typically have a period of being very healthy prior to this
- Can present in adolescence

Question 21

What is phenylketouria?

Answer 21

PKU is an aminoacidopathy (inborn error of protein metabolism)

build up of phenylalanine
from a deficiency in Phenylalanine Hydroxylase (PAH)

occasionally, due to a BH4 metabolism defect
bc Tetrahydrobiopterin (BH4) is a cofactor for PAH

autosomal recessive (as are essentially all metabolic disorders)

Question 22

how does phenylketouria (PKU) present?

Answer 22

• Eczematous rash
• Hypopigmentation
• Musty (“mousy”) odour
• Microcephaly
• Gradual onset of symptoms if missed
  
  • Global developmental delay (GDD)
  • Mood and cognitive disorders

Teratogenic – if mother untreated, infants would be dysmorphic, microcephalic, IUGR, CHD

Question 23

diagnosis of phenylketouria (PKU)?

Answer 23

• Newborn Metabolic Screen (NMS) -PKU is essentially why the NMS exists
• Plasma amino acids (PHE level)
• Urine organic acids

Question 24

Treatment of phenylketouria (PKU)?

Answer 24

Dietary restriction of phenylalanine (lifelong) - phenylalanine formula and medical foods

Monitor blood phenylalanine (PHE) levels

Small amounts of PHE (essential amino acid) in tightly prescribed amounts via breastmilk (titrated with blood PHE levels)

BH4 supplementation
(Tetrahydrobiopterin (BH4) is a cofactor for PAH)

Question 25

Prognosis of phenylketouria?

Answer 25

* Early diagnosis is extremely important! * Phenylalanine is toxic to the developing brain * Given PKU does not present with acute signs/symptoms, if not tested on NMS, these pts are missed, and have gradual progression of developmental delay resulting in irreversible brain injury * With current treatment, affected individuals are in regular classes, hold full time jobs and have families

Question 26

What is homocystinuria?

Answer 26

aminoacidopathy (protein metabolism problem) difficulty breaking down methionine bc of Deficiency in cystathionin b-synthetase Autosomal recessive

Question 27

How does homocystinuria present?

Answer 27

very similar to Marfan's * No acute decompensations * Intellectual disability (different than Marfan's) * tall stature * recurrent thrombosis (different than Marfan's) * ectopia lentis (dislocates down, but in Marfan's dislocates UP)

Question 28

diagnosis of homocystinuria?

Answer 28

* Plasma amino acids * urine organic acids * genetics - CBS gene variants, MTHFR

Question 29

treatment of homocystinuria?

Answer 29

* Life long methionine restriction * Aspirin * B6 (folate)

Question 30

what is maple syrup urine disease?

Answer 30

* Deficiency in branched chain a-ketoacid dehydrogenase (ie, cant break down branched chain amino acids) * Clinical problems are due to elevated leucine * aminoacidopathy (disorder of protein metabolism) * Autosomal recessive

Question 31

how does maple syrup urine disease present?

Answer 31

* Acute decompensations (high leucine intake, or catabolic stress) * Headache, confusion, hallucinations, * poor feeding, lethargy, vomiting * Neonatal hypertonicity * Coma * Maple syrup smell in urine and cerumen (ear wax)

Question 32

How to diagnose maple syrup urine disease?

Answer 32

Ketonuria!!!! (or think OAs) Plasma amino acids, urine organic acids Monitoring leucine levels

Question 33

treatment of maple syrup urine disease?

Answer 33

Acute - Stop leucine intake (NPO) - Stop catabolic stress (High dextrose, IV fluids, lipids, NG feeds) - Dialysis (can dialyze leucine) - Monitor for and protect against cerebral edema Chronic: Life long leucine restriction

Question 34

What is tyrosinemia?

Answer 34

deficiency in Fumarylacetoace Hydrolase (FAH) which is the final enzyme in tyrosine degradation toxic metabolites build up - specifically succinylacetone, which causes liver and kidney damage aminoacidopathy (disorder of protein metabolism)

Question 35

how does tyrosinemia present?

Answer 35

Hepatomegaly, liver failure Renal tubular acidosis (Fanconi syndrome - polyuria, normal anion gap metabolic acidosis, hypophosphatemia) "Neurological Crises" - aLOC, central respiratory failure, weakness Poor growth, rickets

Question 36

Diagnosis of tyrosinemia?

Answer 36

* Urine organic acids (increase in succinylacetone is pathognomic) * Plasma amino acids: elevated tyrosine * Liver: elevated AST/ALT, coagulopathy * Renal Fanconi syndrome (glucosuria, phosphaturia, aminoaciduria)

Question 37

Treatment of tyrosinemia?

Answer 37

Low-tyrosine, low-phenylalanine diet Liver transplant if severe hepatic dysfunction or HCC

Question 38

what are organic acid disorders?

Answer 38

problem with metabolizing organic acids --> build up of organic acids (organic acids are produced from the break down of amino acids) NOTE that you have build up of organic acids Organic acids compete for the NAGS enzyme that brings ammonia into the urea cycle defect So organic acid disorders also causes ammonia to build up Important to note for treatment

Question 39

how do organic acid disorders present?

Answer 39

usually present in first few days of life unwell baby with poor feeding, vomiting, lethargy high anion gap metabolic acidosis (from organic acids) ketosis and lactic acidosis multiorgan failure (hepatomegaly, hepatitis, renal failure, pancreatitis) pancytopenia (neutropenia, anemia, thrombocytopenia)

Question 40

how to diagnose organic acid disorders?

Answer 40

Urine organic acids Acyl carnitine and carnitine profile

Question 41

how to treat organic acid disorders?

Answer 41

stop protein intake Carnitine supplement* promote anabolic state (IV dextrose, insulin, lipids) IV bicarb as usually severely acidotic eliminate ammonia = dialysis and carglumic acid** long term: protein restricted diet, carnitine, sick day management notes: * carnitine increases excretion of organic acids in the urine ** Carglumic acid ("Carbaglu") = see diagram, organic acids use the NAGS enzyme. carbaglu add more of the NAGS enzyme so the urea cycle can work and get rid of ammonia

Question 42

what are the sequalae of organic acid disorders that we need to monitor for?

Answer 42

* CNS: Strokes*, cerebral edema * Cardiac: Myocarditis* * GI – Pancreatitis* * GU - Electrolytes * Heme - Cytopenias * ID – Infection risk *Differs from UCDs

Question 43

what are urea cycle disorders?

Answer 43

problem with one of the enzymes of the urea cycle Breakdown of all protein leads to the production of ammonia and this is toxic to the brain. The urea cycle takes the ammonia and converts it into urea for the kidneys to excrete into the urine the urea cycle is simply 5 enzymes - if one enzyme is missing, the pre-reaction product builds up, the cycle halts and you get hyperammonemia

Question 44

how do urea cycle disorders present?

Answer 44

usually present in first few days of life unwell baby with poor feeding, vomiting, lethargy Hypoglycemia SHOCK-like presentation (multi-organ failure) with LOW urea bc not making urea bc urea cycle not working high ammonia RESPIRATORY ALKALOSIS - tachypnea without WOB *resp alkalosis is key feature of UCD, however if a kid has been encephalopathic for 3 days, they are really sick with end organ dysfunction, you might actually see a metabolic acidosis (but you wouldn't have elevated lactate)

Question 45

how to diagnose urea cycle disorders?

Answer 45

* Ammonia * Serum amino acids * Urine organic acids (example: orotic acid) * Genetics **Any patient with any neuro/psychiatric presentation (decr LOC, encephalopathy, delirium, acute psychosis, change in behaviour/personality) of any age --> ORDER an AMMONIA level! Otherwise you will miss a UCD!**

Question 46

what is the acute treatment for urea cycle disorders?

Answer 46

stop all protein decrease ammonia - dialysis - odium benzoate/sodium phenylacetate (nitrogen scavengers) Promote Anabolic state (IV dextrose, high calories) Carnitine (cofactor of many enzymes)

Question 47

what is the long-term treatment for urea cycle disorders?

Answer 47

□ protein-free diet □ arginine or citrulline (intermediates in the urea cycle, helps the urea cycle go in this pts) □ Sodium or glycerol phenylbutyrate (Ravicti) - oral nitrogen scavenger □ Liver transplant □ Sick day management (need to avoid catabolic states)

Question 48

what are the sequalae of urea cycle disorders that we need to monitor for?

Answer 48

* CNS: Cerebral edema, seizures * Cardiac: Myocarditis * Respiratory: Tachypnea, resp alkalosis * GI: Poor perfusion, secondary hepatitis/failure * GU: Electrolyte disturbance * Heme: Cytopenias * ID: Infection risk (lines, cytopenias)

Question 49

what is Ornithine Transcarbamylase Deficiency (OTC)?

Answer 49

type of urea cycle defect X-linked (so a bit more common than other metabolic disorders, which are usually autosomal recessive)

Question 50

what are fatty acid oxidation defects?

Answer 50

a group of disorders affecting the metabolism of Short, Medium, Long or Very Long chain fatty acids medium chain is the most common (Medium-chain acyl-coenzyme A dehydrogenase (MCAD))

Question 51

how do fatty acid oxidation defects present?

Answer 51

Triad 1. Hypoketotic Hypoglycemia 2. Rhabdomyolysis 3. Arrythmia/Cardiomyopathy hepatitis, hepatic encephalopathy, reye-like, mildly elevated ammonia Normal at birth, developmentally appropriate Presents in infancy or early childhood during prolonged **FASTING**

Question 52

why do we see hypoketotic hypoglycemia in fatty acid oxidation defects?

Answer 52

○ In fatty acid oxidation defects, patient can't get energy from fat, so the body has to pull it from carb (blood glucose) or protein (skeletal muscle, heart muscle) ○ Since babies don't have much muscle, then they burn though their glucose fast --> hypoketotic hypoglycemia is most common presentation in babies (not making ketones since no beta oxidation of fatty acids) ○ older kids start breaking down muscle for energy (from the heart muscle or MSK muscle), so you see cardiomyopathy/arrythmias and rhabdomyolysis

Question 53

what are triggers for fatty acid oxidation defects presentation?

Answer 53

*FASTING* for 4hr in neonate or 12 hr in adult

Question 54

diagnosis of fatty acid oxidation defects?

Answer 54

○ Plasma acylcarnitine profile (tells you how many you have of very long, long, medium chain fatty acids - you will have high numbers of the precursor) ○ Urine organic acids ○ Carnitine (Free and total)

Question 55

treatment of fatty acid oxidation defects?

Answer 55

Stop fat IV dextrose and protein for calories

Question 56

Long term treatment of Long Chain Fatty Acid Oxidation Defects?

Answer 56

- fat-restricted diet - medium chain fat supplementation (MCT oil) - avoidance of fasting - Carnitine (function of carnitine is to transport long-chain fatty acids across the inner mitochondrial membrane, allowing them to be used as fuel for energy production)

Question 57

Long term treatment of Medium Chain Fatty Acid Oxidation Defects?

Answer 57

avoidance of fasting □ MCAD is milder so actually don't need to restrict fat, just need to avoid fasting □ must feed q3h for first 3 months of life □ By 2 yrs old, can fast up to 12 hours (max for lifetime)

Question 58

what is primary carnitine deficiency?

Answer 58

Build up of very long chain fatty acids function of carnitine is to transport long-chain fatty acids across the inner mitochondrial membrane, allowing them to be used as fuel for energy production

Question 59

diagnosis of primary carnitine deficiency?

Answer 59

Plasma carnitine levels Urine organic acids Hypoketotic hypoglycemia

Question 60

treatment of primary carnitine deficiency?

Answer 60

Oral carnitine

Question 61

what is galactosemia?

Answer 61

deficiency in breaking down galactose (recall lactose = galactose + glucose) Sx are from the build up of glactose-1 phosphate

Question 62

how does galactosemia present?

Answer 62

○ Presents in first 10 days of life with jaundice and feeding intolerance ○ Progression to CONJUGATED hyperbilirubinemia, liver failure, bleeding/coagulopathy from liver failure Recurrent E Coli Sepsis (E coli bacteria ferments galactose, for which there is plenty in this condition) cataracts

Question 63

diagnosis of galactosemia?

Answer 63

Newborn Metabolic Screen (NMS) = GALT enzyme activity for screening (False positive in G6PD) Confirmatory Test -elevated erythrocyte galactose-1-phosphate concentration - reduced erythrocyte galactose-1-phosphate uridylyltranserase (GALT) enzyme activity -Genetics (GALT enzyme)

Question 64

treatment of galactosemia?

Answer 64

Lactose free formulas (eg soy or elemental formula) *Removal of galactose improves symptoms rapidly Breast milk is contraindicated in Galactosemia Long term diet: avoid dairy products Experimental: Enzyme Replacement Therapy (ERT)

Question 65

what is hereditary fructose intolerance?

Answer 65

Aldolase B deficiency Presents after eating fructose (eg fruit or meds covered in high-fructose corn syrup)

Question 66

presentation of hereditary fructose intolerance?

Answer 66

Hypoglycemia Vomiting Liver dysfunction

Question 67

treatment of hereditary fructose intolerance?

Answer 67

Avoid fructose

Question 68

what are glycogen storage disorders?

Answer 68

Inability to breakdown glycogen into glucose leads to hypoglycemia and hepatomegaly (glycogen just continues to build up in the liver) Extremely heterogeneous clinical presentations (Type 1 most severe with rhabdo)

Question 69

features of glycogen storage disorders?

Answer 69

1. Hypoglycemia with Hepatomegaly 2. Elevated Triglycerides 3. Hyperuricemia 4. Lactic Acidosis the body needs to raise blood glucose, however it can't break down glycogen into glucose. so they body trying to get more energy ends up making more lactate, uric acid, triglycerides, while remaining hypoglycemic glycogen continues to build up in the liver (hepatomegaly), face (coarse facies), bowels (IBD) Neutropenia

Question 70

How to distinguish urea cycle defects from organic acidemias?

Answer 70

Organic acidemias present with more profound metabolic acidosis (AGMA) whereas primary disorder in urea cycle disorder is respiratory alkalosis Urea cycle disorders have inappropriately low urea, whereas organic acidemias should still have elevated urea in appropriate context Organic acidemias have marked ketonuria (should never have ketones in neonatal period, red flag) Organic acidemias can have pancytopenia and labs suggestive of multiorgan failure (hepatitis, renal failure, pancreatitis) Both have hyperammonemia Both may have hypoglycemia Both may present in neonatal period with lethargy/shock like picture

Question 71

What is GSD 1 (Von Gierke Disease)?

Answer 71

Can't break glycogen stores down into glucose (both glygogenolysis and gluconeogenesis impacted) Glucose 6 phosphate can't be made into glucose so instead it shunts towards increasing pyruvate and increasing lactate and uric acid

Question 72

Presentation of GSD 1?

Answer 72

*Clinical presentation Young (3 months when they start to stretch out nighttime feeds) Progressively poor feeding Lethargy, seizures Growth failure *Exam Cherubic/ doll facies Lethargy, pale May have weakness May have hepatomegaly *labs Ketotic hypoglycemia Lactic acidosis Hyperuricemia Hypertriglyceridemia Type 1b has neutropenia

Question 73

Long term treatment of GSD 1?

Answer 73

Cornstarch Continuous feeds Sick day monitoring

Question 74

Long term complications of GSD 1?

Answer 74

Neutropenia and frequent infections Hepatic adenomas Renal insufficiency IBD

Question 75

What is GSD 2 (Pompe disease) ?

Answer 75

Deficiency of enzymes in lysosomes, leads to accumulation of glycogen (skeletal, cardiac, smooth muscle) Classic infantile onset - presents first 2 months of life - hypotonia, generalized muscle weakness, cardiomegaly, HOCM, FTT, resp distress, hearing loss - death in the first year of life from progressive left ventricular outflow tract obstruction Classic presetation on exam: - cardiomegaly - hypotonic infant - super short PR on ECG with huge voltages

Question 76

Treatment for Pompe disease?

Answer 76

Enzyme replacement therapy within 1st 6 months

Question 77

What is GSD 5 (McArdle disease)?

Answer 77

Deficiency in myophosphorylase

Question 78

Clinical presentation of McArdle (GSD 5)?

Answer 78

Adolescent onset Exercise induced muscle pain and rhabdomyolysis Think about it when unexplained elevated CK "2nd wind phenomenon"

Question 79

Diagnosis / Investigations in McArdle?

Answer 79

Elevated CK Muscle biopsy shows deficient myophosphorylase activity and glycogen accumulation Genetics (PYGM gene)

Question 80

Management of GSD 5 (McArdle)?

Answer 80

Avoid strenuous activity Rhabdomyolysis management

Question 81

Features of Adrenoleukodystrophy?

Answer 81

X-linked Deficiency in VLCFA oxidation School aged onset Developmental regression New spasticity Adrenal failure (may present with AI, bronzed skin etc) Workup: MRI head, VLCFAs

Question 82

Features of Zellweger syndrome?

Answer 82

Absent peroxisomes Dysmorphic Hypotonia Hearing and vision defects Seizures Very wide fontanelle Liver disease MRI shows leukodystrophy Don't survive infancy Workup: MRI head, VLCFAs

Question 83

Features of mucopolysaccharidoses?

Answer 83

Progressive symptoms, wide spectrum of severity Normal at birth Coarse facial features Corneal clouding Bony deformities, short stature Developmental regression Visceromegaly Hearing and visual defects Umbilical and inguinal hernias Xray - dysostosis multiplex (bone dysplasia) Workup: Urine glycosaminoglycan (GAG), oligosaccharides, genetic testing, lymphocyte or fibroblast enzymatic activity Treat: Enzyme replacement therapy Stem cell transplant Types: Type 1 = Hurler Syndrome (most severe) Type 2 = Hunter Syndrome (less severe)

Question 84

Examples of sphingolipidoses?

Answer 84

Tay-Sachs - weaness, exaggerated startle reflex, myoclonus, developmental regression, cherry red spots Gaucher - marrow failure, HSM, Parkonsism, early onset type 2 Fabry Krabbe

Question 85

Features of mitochondrial disorders?

Answer 85

Elevated lactate Cardiomyopathies Recurrent stroke-like episodes Need muscle biopsy for workup Typically maternal inheritance

Question 86

DDx for hyperammonemia?

Answer 86

IEM - urea cycle defects - organic acidemias - FAODs - hereditary fructose intolerance - others Liver - liver failure - sepsis - perinatal depression / hypoxia Iatrogenic - VPA - TPN Other - Transient hyperammonemia of the newborn