Week 3 disorders

Question 1

Autosomal Recessive
Symptom: developmental delay starts @ 3-4 mths
Cause: Phe cant be metabolized, enzyme deficiency for PAH, blocked conversion of PHE to tyrosine, buildup of PHE is toxic
Tests: blood level of PHE-elevated AA, elevation of diagnostic AA on AA quantification
Treatment: diet low in protein

Answer 1

Phenylketonuria (PKU)

Question 2

Autosomal recessive
Symptom: low pH, vomiting, dehydration, lethargy, weak muscle tone, low weight, coma and death if left untreated.
Cause: lack of methylmalonyl-CoA mutase enzyme activity which converts methylmalonyl-CoA into succinyl-CoA. Methylmalonyl-CoA is produced in the catabolism of certain AA, cholesterol and odd-chain fatty acids. Need vit B12 for enzyme to work. cant break down fats or proteins
Tests: methylmalonic acid is elevated on urine organic acid quantitation
Treatment: diet low in protein, liver transplant and ammonia scavenger medications (in severe circumstances)

Answer 2

Methylmalonic Aciduria

Question 3

X-linked recessive(more common in males)
Symptom: enzymatic defects early in the cycle result in severe, dangerous hyperammonemia in the neonate. can result in neurologic damage
Cause: defect in pathway converting toxic ammonia to nontoxic urea
Tests: elevation of ammonia and diagnostic amino acid
Treatment: diet low in protein, ammonia scavenger medications. In SEVERE cases: dialysis, liver transplant

Answer 3

Ornithine Transcarbamylase enzyme (OTC)

Question 4

Autosomal recessive
Symptoms: ingestion of fructose leads to vomiting and hypoglycemia, chronic ingestion causes hepatomegaly and renal dysfunction.
Cause: fructoaldolase (aldolase B) metabolizes fructose to glucose, fructose is a component of sucrose, mutation in ALDOB gene that codes for aldolase B enzyme
Test: find out when baby first has fruit juice, molecular analysis of aldolase B
Treatment: restricting fruit, vegetables, corn syrup, table sugar to prevent symptoms

Answer 4

Hereditary Fructose Intolerance (HFI)

Question 5

X linked recessive
Symptoms: neurologic dysfxn and self-mutilation behavior. May also have gout b/c elevated uric acid levels (uric acid develops into crystals, accumulates in joints)
Cause: disorder of purine reclamation, defect in hypoxanthine-guanine phosphoribosyltransferase activity (HGPRT). Purines are broken down into uric acid
Test: elevated levels of uric acid and molecular analysis of HGPRT, clinical suspicion
Treatment: low purine diet, allopurinol as well as medicine for treating neurological symptoms

Answer 5

Lesch-Nyhan Disease

Question 6

Autosomal recessive
Symptoms: child w/ lethargy and vomiting after fasting, hypoketotic, hypoglycemia, other disorders have cardiac and/or hepatic involvement
Cause: many disorders: VLCAD,LCAD, most common is medium chain acyl-CoA dehydrogenase deficiency (MCAD)
Test: diagnostic intermediates on urine organic acid quantitations
Treatment: avoidance of fasting and rapid treatment of hypoglycemia

Answer 6

Medium acyl-CoA dehydrogenase (MCAD)

Question 7

Autosomal recessive
Symptoms: alopecia, dermatitis, deafness, seizures, neurological deterioration starting @ 4-6 mths
Cause: disorder in the reclamation or recycling of the vitamin biotin which is important in carboxylation rxns, defect results in biotin deficiency
Test: clinical suspicion and enzyme assay of biotinidase
Treatment: biotin supplementation

Answer 7

Biotinidase deficiency

Question 8

X linked recessive (mostly in males)
Symptoms: not a lot of hair and hair is twisted, failure to gain weight, failure to thrive, deterioration of NS
Cause: severe neurodegenerative disorder beginning in first months of life, inability to absorb copper across the intestinal epithelium, copper deficiency
Test: relevant lab studies: low ceruloplasmin and copper
Treatment: none @ the moment

Answer 8

Menke disease

Question 9

X linked recessive
Symptoms: macrocephaly, large face, thickened joints, heart valves/walls, walls of lungs
Causes: alpha-iduronidase sulfatase defect in lysosome, accumulate mucopolysaccharides such as dermatan and heparin sulfate
Test: enzyme assay of alpha-iduronidase sulfatase
Treatment: enzyme replacement therapy- Eleprase- bloodstream injection to lysosome- need injection every week

Answer 9

Hunter syndrome

Question 10

Autosomal recessive
Symptoms: hypotonic, large forehead
Causes: defects in formation of peroxisomes or an isolated peroxisomal enzyme defect- no peroxisome formed, so long fatty acid chains floating around
Test: elevated very long chain FAs and phytanic acid
Treatment: no treatment-fatal

Answer 10

Zellweger syndrome

Question 11

Autosomal recessive
Symptoms: thick mucous, pneumonia, nasal polyposis
Causes: defect in chloride channel CFTR fxn producing thick mucous
Test: perform sweat chloride channel test
Treatment: antibiotics and other things to make pt more comfortable

Answer 11

Cystic fibrosis

Question 12

Symptoms: sickle shaped RBCs, sickle cells obstruct capillary blood flow causing pain
Cause: point mutation in beta-hemoglobin that changes glutamic acid to valine producing HbS- heterzygotes are asymptomatic unless exposed to low O2 situations-protective agains malaria
Test: none??
Treatment: medications, bone marrow transplant-only in severe circumstances

Answer 12

Sickle Cell anemia

Question 13

Symptoms: severe neurodegenerative disorder, high in Ashkenazic Jewish pop
Cause: defective lysosome- hexosaminidase A which degrades GM2-gangliosides in neurons
Test: none??
Treatment: none @ the moment, just treatment for side affects

Answer 13

Tay-Sachs Disease

Question 14

Symptoms: neurotoxic symptoms in the first weeks of life; high in Mennonite populations
Cause: inborn error of leucine, isoleucine, and valine metabolism- (one enzyme defective for the 3 AA)- due to genetic drift/founder effect in small populations
Test: none??
Treatment: low protein diet

Answer 14

Maple Syrup Urine disease

Question 15

Symptoms: degenerative neurological disease w/ hepatic and/or neurological dysfxn
Cause: mutation in MPV17 gene-important in mitochondria fxn- Navajo had reduced population size so frequency of MPV17 increased due to genetic drift/founder effect

Answer 15

Navajo Neurohepatopathy

Question 16

Deformation- unusual forces on normal tissue movement of tissue but no breakdown
Not genetic
mechanical forces result in altered morphogenesis, usually molding
Treatment: crib/helmet can help

Answer 16

Uterine constraint/breech position/positional plagiocephaly

Question 17

a normal fetus is subjected to a destructive problem causing breakdown or loss of normal tissue due to a cause: vascular, infection, mechanical problems (hands/ankles)
Usually sporadic

Answer 17

Disruption breakdown of normal tissue

Question 18

poor formation of tissue
single localized abnormality in formation of tissue that initiates a chain of subsequent defects
can be nearly normal or more severe
can suggest syndromic diagnosis

Answer 18

Malformation

Question 19

x chromosome inactivation
abnormal organization of cells into tissues
abnormal migration of cells
decreased sweating, little/no hair/teeth, women mildlyl affected

Answer 19

Hypohidrotic ectodermal dysplasia

Question 20

abnormalities in hormones, nerves or CT
Mechanical problem
reported in 350 syndromes
failure of descent of testes

Answer 20

Cryptorchidism

Question 21

Autosomal Dominant
Symptoms: growth of numerous benign tumors, cardiac rhabdomyoma, ungual fibroma, facial angiofibromas(look like acne scars) ashleaf spots (hyperpigmentation on skin), seizures
Causes: mutations in TSC1 or TSC2 gene that codes for proteins to help regulate cell growth and size

Answer 21

Tuberous Sclerosis

Question 22

Autosomal dominant
Symptoms: Type I: heterchromia, hypertelorism, deafness, white forlock
Type IV: Severe constipation or complete intestinal blockage in Hirschsprung disease
Causes: Type I- mutation in PAX3 gene
Type IV: several genes
Hirschsprung disease (absence of nerves in parts of the intestine, aka anganglionic megacolon)

Answer 22

Waardenberg Syndrome Type (I-IV)

Question 23

Symptoms: holoprosencephaly

clefting, missing or malformed midline strucutres, cyclopia, single central incisor, absent frenulum

Answer 23

Sonich Hedgehog (SHH)

Question 24

X-linked recessive
mutation in gene coding for dsytrophin- (mutations are nonsense, frame-shift, splicing or large deletions)
1/3 are new mutations-rest have female carrier mothers
women can have germline mosaicism and not show any symptoms

Answer 24

Duchenne Muscular Dystrophy

Question 25

mutations cause partially defective dystrophin mutation (point mutations, in-frame duplications and deletions, rearrangements and small deletions)
can see low levels of

Answer 25

Becker Muscular dystrophy (BMD)