Neurology
This condition is the primary differential for a case involving a young male (4-6yo) who has recent leg weakness, trouble rising from sitting, and high CK on blood test.
Duchenne muscular dystrophy
Pierre robin sequence is often a part of this genetic condition
This DSD is considered an emergency when identified in a newborn
CAH
1. What is the primary marker for metabolic acidosis as obtained from a blood sample?
2. How do we know if we are suspicious of an IEM vs. another cause of acidosis?
1. CO2 / bicarbonate
2. Anion gap elevated
***slide 19 of intro to metabolism
Which MPS is expected to have typical intelligence?
MPS IV (morquio)
also MPS VI (less common)
A child with lisch nodules and freckling in the groin and armpits should receive screening for what type of cancer in childhood?
optic glioma
For a child with a neonatal history of omphalocele and macrosomia whose initial methylation testing was negative, what additional test would you request in order to complete the molecular workup for the suspected diagnosis?
What is CDKN1C sequencing?
In a proband with suspected Kearns Sayre Syndrome, a VUS is found in a mitochondrial gene and is homoplasmic in both the proband and mother. How suspicious are you of this variant?
not very suspicious
What is a potential explanation for an NBS concerning for galactosemia who seems to be clinically unaffected?
duarte galactosemia
Name three primary organ systems affected by Gaucher Disease?
Blood, liver/spleen (hepatosplenomegaly), Bones (crisis, fracture, pathognomonic deformity**)
With severe type, neuro sx in childhood as well
"BOB Has Gaucher" (BOB=Blood, Organs, Bones)
Valproic Acid (a common anti epileptic medication) is contraindicated for people with this genetic condition, which can cause epilepsy.
POLG
Most genetic conditions affecting the glucose / carbohydrate metabolism cause symptoms when a patient is fasting. Name an exception
HFI
patient presents with history of discordant NIPT showing XY while imaging and external genitalia suggest female anatomy. At birth, patient suspected to have bilateral inguinal hernias, although ultrasound of the region increases suspicion for testes and is unable to visualize a uterus. What single gene testing would you like to start with?
AR
A 3mo child presents to the ED with lethargy and vomiting following a seizure like event. patient has had a fever for ~2 days prior. Labs in ED notable for metabolic acidosis, elevated anion gap, high ammonia, low white blood cells, elevated amylase and lipase, and low platelets. What type of metabolic labs would be MOST important to order?
Urine Organic Acids
After a positive NBS for pompe disease, what organ system should be examined first and why?
Cardiac system --> looking for cardiomegaly
chest xray can also give clues to resp. health
Echo can let us know about HCM
this can help us distinguish IOPD from LOPD
For a case involving a neonate with severe hypotonia (to the point of causing respiratory distress and dysphagia), where WES has been negative, what three additional genetic tests do you need to order?
SMA sequencing
MS-MLPA for 15q11.2
DMPK repeat analysis
This potentially life threatening symptom of achondroplasia requires careful monitoring in infancy / childhood and sometimes even surgery
foramen magnum stenosis / narrowing of the cranio cervical junction
Patient in mid 20s presents with progressive visual failure. Family history is noncontributory, although they note mom's family is French Canadian. What mitochondrial condition might you want to test for?
LHON (leber hereditary optic neuropathy)
Compare the lab findings that would help you distinguish GSDs from FAODs - what kind of sample would you need?
Blood and urine samples to see hypoketotic vs ketotic hypoglycemia
ketones seen in urine primarily
Newborn screen was positive for XALD in a 6 day old male. You order follow up testing including plasmalogens and phytanic acid while you are waiting for ABCD1 sequencing results. If this is a true positive, what would you expect them to show?
both plasmalogens and phytanic acid normal.
For a child with severe kidney problems that were first noted in utero, skin findings including hypopigmented macules, epilepsy, and abnormal brain MRI, what testing would you like to order?
consider CMA for TSC2/PKD1 contiguous gene deletion syndrome
Besides differences in the cranial sutures, name 2 other organ systems which can be involved with apert syndrome
Heart
kidney
airway obstruction
cervical spin fusion
CNS malformations
Cascade testing is being completed in a family with a known history of LHON. 10 yo sibling of the proband has 40% heteroplasmy for the variant, do they have LHON?
Probably not
Name 2 conditions which can be incidentally picks up by newborn screening and explain how?
22q11.2 deletion syndrome (absent thymus--> SCID screen)
late onset Pompe
Zellweger Syndrome
Duarte Galactosemia
Maternal conditions (i.e. carnitine uptake def)
A child admitted with a suspected Urea Cycle Disorders has absent citrulline and elevated orotic acid on PAAs. There is no known family history of metabolic condition or special diet, although mom is vegetarian. What is the inheritance pattern of the condition?
X linked