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Genetic Counseling > Biochem/metabolic > Flashcards

Biochem/metabolic Flashcards

1
Q

Sweaty foot odor

A

Isovaleric acidemia

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2
Q

When should you consider a metabolic disorder?

A
  1. Catastrophic neonatal presentation
  2. Biochemical disturbances (ex: acidosis, hyperammonemia, hypoglycemia)
  3. Liver disease
  4. Neurologic features
  5. Myopathy/cardiomyopathy
  6. Signs of a storage disease (ex: hepatosplenomegaly, course facies)
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3
Q

How is homocystinuria different than Marfan syndrome?

A

Individuals with homocystinuria have stiff joints (MFS are lax), they tend to have some degree of DD/ID, and they are at risk for thrombosis (often cause of death)

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4
Q

Why do defects in carnitine transport resemble fatty acid oxidation defects?

A

Because carnitine is required to bring long chain fatty acids into the mitochondrion so that enzymes can work on the fatty acid to break off ketone bodies (which muscles need in times of fasting!)

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5
Q

Why is MTC oil a treatment for VLCAD deficiency?

A

Because MCT (medium chain triglycerides) can get into the mitochondrion and essentially bypass the need for working enzymes to break very long chains down into long chains, then to medium chains, etc… (so that muscles continue to get energy!)

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6
Q

What does the neonatal catastrophe look like?

A

Feeding problems, vomiting, lethargy, coma, seizures, rapid breathing, usually hypotonia and hyporeflexia, and may appear septic

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7
Q

What are the chronic problems for those who have an urea cycle disorder?

A

Poor feeding/anorexia, protein aversion, vomiting, may have hypotonia and/or develop delays

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8
Q

What are the problems for those who have an urea cycle disorder when they have a crisis event?

A

Metabolic acidosis, high ammonia, hypoglycemia, episodes of biochemical decompensation

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9
Q

What are the chronic problems for those who have an organic acidemia?

A

Poor feeding/anorexia, vomiting, hypotonia, develop delays/MR, may have protein aversion,

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10
Q

What are the problems for those who have an organic acidemia when they have a crisis event?

A

Vomiting, lethargy/coma, seizures, metabolic ketoacidosis, may have high ammonia, may have hypoglycemia

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11
Q

Zellweger Syndrome

A

Prenatal onset, dysmorphic, hypotonia, seizures, liver disease, death within months

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12
Q

Most metabolic/biochemical disorders follow which inheritance pattern?

A

Autosomal Recessive

exceptions - OTC, Fabry, X-lined adrenoleukodystrophy, Menkes, pyruvated dehydrogenase deficiency, Lesch Nyhan, Barth, glycerol kinase deficiency and Hunter syndromes are X-linked
acute intermittent porphyria is auto dominant

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13
Q

What are the six main categories of biochemical disorders?

A

UFOCAL

Urea Cycle, Fatty Acid Oxidation, Organic Acid, Carbohydrate, Amino Acid, Lysosomal Storage Disorders

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14
Q

What metabolic disorders can be detected in utero?

A

Pompe (enlarged heart fills the chest cavity)

Glutaric Acidemia Type II (rocker bottom feet, large cystic kidneys)

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15
Q

What is the “intoxication phenotype” that presents with amino acid/organic acid/urea cycle/fatty acid disorders?

A

lethargy, vomiting, poor feeding, seizures, encephalopathy (altered mental state), coma

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16
Q

Microcephaly, mental retardation, congenital heart disease, IGUR and postnatal growth retardation can be caused by high levels of what amino acid (teratogenic effect) during pregnancy?

A

Phenylalanine - poorly controlled PKU by mother causes maternal PKU phenotype (child does not have to have PKU to develop this phenotype)

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17
Q

Carbohydrate disorders often present with “energy deficiency” symptoms due to defect in carb metabolism. What are these symptoms?

A

lethargy, hypoglycemia, encephalopathy, liver dysfunction, myopathy, cardiomyopathy

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18
Q

What is the “storage phenotype” associated with lysosomal storage disorders?

A

coarse facial features, developmental regression, MR, hepatomegaly, splenomegaly, cardiomyopathy, kidney failure, bone disease, muscle weakness

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19
Q

What disorder has a locker room odor?

Also only inborn error with dysmorphic features per Dr. N’s lecture– rocker bottom feet, etc…

A

Glutaric Acidemia type II

(Sweaty feet is isovaleric acidemia)
Add’l dysmorphic features: high forehead, hypertelorism, large cystic kidneys, GI defects, normal GU, abdominal wall muscle defects

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20
Q

What has a musty odor (if left untreated)?

A

PKU

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21
Q

What does MELAS stand for?

A

Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes

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22
Q

What is Pearson syndrome?

A

Mitochondrial disease caused by deletion on mtDNA (usually sporadic); symptoms similar to Kearns-Sayre or Leigh syndrome.

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23
Q

Name the amino acid disorder: caused by deficit in ANY of the 6 essential BCKAD complex enzymes, elevated branch chain AA’s (leucine, isoleucine, valine), intoxication phenotype if untreated, classic infantile, intermittant, and intermediate (common among Hispanics) forms. Liver transplant an option, founder effect among Mennonites in PA.

A

Maple syrup urine disease– also sweet smelling urine, but that would be too easy ;)

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24
Q

What is a normal PHE (phenylalanine) level?

A

30-90 umols/L
benign hyperPHE to 600 umols/L
>600 umols/L= detrimental
>1000 umols/L=Classic PKU (severe enzyme deficiency)

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25
Q

Name the metabolic disorder & its treatment:
normal at birth, onset of GI problems, liver cirrhosis, and cataracts w/in weeks, energy deficient phenotype, susceptible to E.coli sepsis, premature ovarian failure, N314D variant associated with residual enzyme function 5-20%

A

Galactosemia! A carb disorder. Defective GALT enzyme. Compound heterozygotes w/ Duarte variant (N314D) confers 5-20% residual activity– much less severe phenotype, but may still have some symptoms.
Q188R is most common allele among N Am. Caucasians (no residual activity).
**Diet for life with galactose restriction.

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26
Q

What is the most common fatty acid oxidation disorder?

A

MCAD!

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27
Q

Describe MCAD’s symptoms and treatment

A

In times of illness and/or fasting:
hypoketotic hypoglycemia; hepatomegaly and liver disease; lethargy; seizures, coma; sudden death
Treatment: low fat diet (20-25%), emergent treatment, no fasting, carnitine

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28
Q

Why do fatty acid oxidation disorders typically present in times of crisis (aka illness or fasting)?

A

The fatty acid oxidation pathway is typically used as an ALTERNATE energy source with the body is out of glucose (fasting) or has increased energy needs (illness)

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29
Q

Broadly, what is a lysosomal storage disorder?

A

Lysosome is the cell’s trashcan; LSD’s result when an enzyme in the lysosome is nonfunctional; results in accumulation of ‘waste’ in the lysosome; results in DISTENSION of cell and DISRUPTION of other cellular functions–> storage phenotype.

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30
Q

What kind of disorders are Tay-Sachs, Pompe, and Fabry disease?

A

Lysosomal storage disorders (LSD’s)

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31
Q

What percentage of female carriers of OTC (X-linked urea cycle disorder) are manifesting heterozygotes?

A

10-15%

32
Q

Name the metabolic dz:

type 1 associated with increased carrier frequency in Quebec and Scandinavia, cabbage-like odor, can be treated pharmaceutically (NTBC) or by liver transplant, caused by deficiency of FAH.

A

Tyrosinemia (an AA disorder)

33
Q

Name the metabolic dz:

Due to defect in CBS (classic form) or 5MeTHF, elevated incidence in Ireland, features may be similar to MFS, also have stroke… treat by diet low in methionine and 1/2 may respond to B6 cofactor supplementation.

A

Homocystinuria

34
Q

You are suspicious of homocystinuria.. what must you do to confirm the diagnosis?

A

Plasma AA’s alone CANNOT measure homocysteine levels.

Need to order homocysteine-methionine panel.

35
Q

Name the metabolic dz:
caused by increased levels of glycine, neonatal presentation begins with hiccups on DOL 1/2, progress quickly to seizures, apnea, intubation… No treatment. If kept on ventilator, vegetative state occurs w/ severe MR, seizures (heroic efforts not recommended).

A

Nonketotic hyperglycenemia

36
Q

How do you differentiate nonketotic hyperglycenimia from an OA disorder or liver dysfunction? (both of which may also caused increased glycine levels)

A

Must look at glycine levels in blood (serum) AND CSF.

If both are elevated–> nonketotic hyperglycenemia and end heroic efforts!

37
Q

Name the metabolic dz:

very high ammonia causes sepsis-like symptoms, aversion to meat, female carriers may be symptomatic, diagnosis by elevated ammonium (tricky test.. must be put on ice immediately or accuracy inhibited). “frequent flyers to the ER” where emergent treatment by ECMO is important to decrease ammonia levels.

A

OTC!

38
Q

Name the CATEGORY of metabolic dz:

diagnosis based on presence of a substance that is not normally present in ANY amount, lactic acidemia may be a presenting sign, ammonium may be elevated, bone marrow suppression common, commonly result from defects in LEUCINE metabolism at various stages, carnitine often helpful. Patients often smell funny.

A

Organic acid disorders

OA’s detected in urine by mass spec.

39
Q

Name the metabolic dz:

aka ketotic hyperglycinemia, due to defect in cobalamin

episodes caused by too much protein

severe metabolic acidosis that is poorly responsive to treatment, may present as neonatal sepsis picture, hepatomegaly, bone marrow suppression, lethargy, vom, seizures, decreased feeding

Results in elevated glycine in serum AA’s AND propionic acid in urine OA’s, increased ammonium.

Treat by low protein diet, biotin supplementation, increased calories (non-protein) that may lead to obesity, carnitine, sodium bicarbonate (to counteract acidosis).

A

Propionic acidemia

40
Q

Name the metabolic dz:

due to defect in B12 OR mutase (more severe pheno & neonatal presentation)

FTT, lethargy, recurrent vomiting, hepatomegaly, MR, coma.

See elevated ammonium, elevated glycine, bone marrow suppression, metabolic acidosis, with NORMAL serum cobalamin, increased ketones, METHYLMALONIC acid in urine or blood.

Treat by low protein diet with carnitine and sometimes B12

A

Methylmalonic acidemia.

41
Q

What is the biochemical basis (generally speaking) of a glycogen storage disease?

A

We all store glycogen (lots of glucose molecules hooked and branched together) in our liver and muscles for use as a source of glucose in times of fasting or sustained exercise.

People with glycogen storage disorders have a deficiency in one of the enzymes necessary to access their glycogen and break it back down for energy.

We see distinct hepatic-hypoglycemia (liver) and muscle forms of GSD’s. Type 4(IV) (Anderson dz) is a hybrid liver-muscle GSD.

42
Q

What are the hepatic-hypoglycemia forms of glycogen storage disease?

A

(1a, 1b, 3, 6)
Type 1a aka von Gierke disease- the classic form of GSD.

characteristic hepatomegaly, hypoglycemia, short stature, delayed puberty, hepatic adenomas w/potential for malignancy (must do abd u/s), and cherub cheek w/vascular pattern.

Type 1b: immune issues 2* to neutropenia

Type III: less severe than Type 1, plus mild muscle weakness that may include mild cardiomyopathy (typically not life threatening). aka Cori disease.

Type VI: generally mild disease.

43
Q

How do you treat the hepatic-hypoglycemic forms of glycogen storage disorders?

A

frequent feeds, avoid simple sugars (sucrose and lactose) in order to avoid rebound effect, treat with raw cornstarch for slow release of glucose, infants treated with continuous drip feeds at night, can now generally have normal LE.

44
Q

What are more common- the hepatic-hypoglycemic forms of glycogen storage disorders, or the muscle forms?

A

Hepatic-hypoglycemic

Also, muscle forms may be more likely to go undiagnosed.

45
Q

What are the muscle forms of glycogen storage disease?

A

5 (V) and 7 (VII)

Type V: aka McArdle disease. primarily affects the muscles w/ pain and cramps. See increased CPK and muscle degradation. phosphorylase def.

Type VII: similar symptoms. phosphofructokinase def.

During crisis, muscles can break down leading to ‘Coca-cola urine’ and kidney damage.–> may not be diagnosed until this time.

46
Q

How do you treat the muscle forms of glycogen storage disorders?

A

Give simple sugars (glucose/fructose) prior to exercise; consider avoidance of exercise (or at least limiting).

47
Q

Describe Type IV GSD (Anderson dz)

A

A hybrid liver/muscle form:
deficiency of brancher enzyme–> very long chains of glucose but inability to build into actual GLYCOGEN molecule, which also involves branches).

very rare; worst prognosis of all GSD’s.

Results in muscle weakness, liver cirrhosis and failure, death. NO hypoglycemia seen (unlike the isolated hepatic forms).

Liver transplant may be an option.

48
Q

How do you diagnose a lysosomal storage disorder?

A

Enzyme assay (measure enzyme activity on dried blood spots or leukocytes, can also use skin fibroblasts, urine, AF)

49
Q

This inborn error of metabolism is technically both a glycogen storage AND a lysosomal storage disease…

A

Pompe!
The defect is in lysosomal alpha-glucosidase
Results in inability to degrade GLYCOGEN inside the LYSOSOME.

50
Q

Name the metabolic dz:

presents with enlarged heart and tongue, may or may not be detectable in utero depending on severity

can be ‘later-onset’–> considered so if after 12 months, main symptom at that time is muscle weakness

ERT IS available; extends like by ~1 year per Dr. N.

A

Pompe disease

51
Q

What, generally, is the biochemical basis of the mucopolysaccharidoses (MPS)?

A

-inability to degrade glycosaminoglycans (aka mucopolysaccharides) in the lysosome– they build up. (MPS’s are LSD’s.)

-will spill the undegraded glycosaminoglycans–the ‘sulfates’– into urine…
(heparan/keratan/chondroitin/dermatan sulfate)

-NO clear correlation between residual enzyme activity and clinical phenotype (cannot rely on %/numbers from the assay to determine prognosis)

52
Q

The most severe presentation of alpha-L-iduronidase deficiency.

A

Hurler syndrome aka MPS I H. deficiency of the enzyme in ALL tissues.

AR

differentiating features: may be coarse even at birth, hirsutism, umbilical/inguinal hernias possible, gum hypertrophy, motor and developmental regression beginning at 2-5 years, “oar shaped” ribs, arachnoid cysts, placid demeanor typically, death at age 8-10 years from heart failure or resp. infection.

May treat with bone marrow transplantation, but not very successful per Dr. N.

53
Q

The least severe presentation of alpha-L-iduronidase deficiency.

A

Scheie syndrome aka MPS I S.
These individuals do have some enzyme function. Typically normal intelligence and normal lifespan.
Not dx until 10-20 years usually.

AR

ERT available to help with main issues– joints and vision (because brain is unaffected– ERT does not cross BBB)

Symptoms: coarsening facies, cloudy corneas, infiltration of aortic valve, claw hand, joint contractures, broad short hands and feet, hirsute, hearing problems.

54
Q

the intermediate presentation of alpha-L-iduronidase deficiency

A

Hurler-Scheie syndrome:

normal IQ, short stature, hepatosplenomegaly, joint problems. Eventual death from deposits in heart and lungs.

dermatan sulfate and heparan sulfate spilled into urine

may need treatment by heart valve replacement surgery and ERT.

55
Q

How do you distinguish Hunter (MPS II) from Hurler (MPS I H) syndrome?

A

1) “Hunters need good eyesight”– NO cloudy corneas in Hunter syndrome, only Hurler.
2) Even severe Hunter syndrome has a more gradual onset of symptoms than Hurler.
3) NO affected females with Hunter syndrome (X-linked)
4) Hunter syndrome patients have a less severe ‘gibbus’ (humpback)

5) And different enzyme deficiencies (assay):
Hurler: alpha-L-iduronidase deficiency
Hunter: iduronate sulfatase deficiency

56
Q 
This mucopolysaccharidosis (MPS) can be caused by defects in any 1 of 4 enzymes important to the degradation of heparan sulfate and is characterized by NEUROLOGIC rather than SOMATIC issues that may range in severity from mild to severe,
Also:
generally healthy until 2-6 years of age.  Then loss of milestones w/: aggression, hyperactivity, coarsening of features, hirsutism, sleep disturbance, HSM, stiffness, seizures, severe hearing loss, dementia that progresses to vegetative state, die from heart failure or pneumonia, but live a long time (30-40 years).
A

Sanfillipo syndrome (MPS III)

Note: 1:10 carrier frequency in Cayman Islands for most severe form… also increased incidence in Netherlands and British Columbia.

57
Q

This mucopolysaccharidosis (MPS) is also know as “short-trunk dwarfism” (normal length arms and legs) and can be caused by defects in either of 2 enzymes (forms A and B)

-Variable IQ (brain may be affected)
-MILD coarsening
-Skeletal abnormalities including:
Odontoid hypoplasia (cervical vertebrae) may lead to quadripilegia due to compression of the spinal cord.
-cloudy corneas and joint LAXITY (rather than contractures)
-widely spaced teeth and thin enamel.
-inguinal hernia
-HSM
-Aortic valve issues
-keratan sulfate in urine

A

MPS IV aka Morquio syndrome

58
Q

This mucopolysaccharidosis (MPS) is due to deficiency of N-acetylgalactosamine (only 1 associated enzyme), but has both mild (early death) and severe (live to 20’s or 30’s) forms.

  • NORMAL IQ
  • coarse facies
  • short stature
  • joint stiffness
  • corneal opacity
  • HSM
  • skeletal abnormalities including genu valgum (knock knees)
  • small wide spaced teeth
  • frequent URI’s and diarrhea
  • may have macrocephaly

-ERT IS an option, because brain is unaffected in this MPS.

A

MPS VI aka Maroteaux-Lamy syndrome

59
Q

This mucopolysaccharidosis (MPS) is caused by deficiency of beta-glucorinidase and:

  • may present with hydrops fetalis prenatally
  • “oar-like” ribs or flaring of lower ribs
  • gibbus
  • hernias
  • moderate to severe MR
  • coarse facies and corneal clouding by 7 months (early)
  • excrete dermatan, herparan, and chondroitin sulfates
  • extremely rare
A

MPS VII aka SLY SYNDROME

60
Q

What are the three types of GM2 Gangliosidosis, and briefly, what is their biochemical mechanism/cause?

A

3 types are:

1) Tay-Sachs (HEXA mutation; alpha subunit)
2) Sandhoff (HEXB mutation; beta subunit)
3) GM2 Activator deficiency (deficiency of GM2 activator!)

Problem: need all 3 to cleave GM2 gangliosides in the lysosome; primarily affects the brain. (these are lysosomal storage diseases)

61
Q

What is the most common GM2 gangliosidosis?

A

Tay-Sachs (1: 100,000)

62
Q

How do you differentiate between Tay Sachs and Sandhoff?

A

1) Enzyme assay
(Tay Sachs by deficiency of hexosaminadase A only; Sandhoff by deficiency of hexosaminadase A AND B)
2) Genetic testing of HEXA and HEXB
3) Sandhoff disease has involvement outside of the nervous system– organomegaly, skeletal abnormalities

  • Note: BOTH have cherry red macula
  • Also note: if both hexosaminadase A and B levels are normal, consider GM2 activator deficiency- identical phenotype to Tay Sachs.
63
Q

How is GM1 gangliosidosis related to Morquio syndrome B?

A

Both are caused by deficiency of beta-galactosidase and mutations in GLB1
–> either the mucopolysaccharidosis phenotype (Morquio) or the gangliosidosis phenotype (GM1).

64
Q

Name the metabolic dz:

  • Caused by beta galactosidase deficiency
  • cherry red spot
  • HSM
  • Skeletal changes
  • neurologic deterioration with death by 2 years in infantile form
  • Also has juvenile and adult form
  • No treatment.
A

GM1 gangliosidosis!

very similar to Tay Sachs if infantile presentation, but Tay Sachs results from hexosaminadase A deficiency.

65
Q

Ashkenazi Jews have 3 common mutations for this metabolic disease… speculated to be due to a founder effect and/or heterozygote advantage for tuberculosis. This dz also possesses geno/pheno correlations with a later-onset form.

Motor weakness at 3-5 months, increased startle reflex… cherry red macula

A

Tay Sachs

66
Q

Name the metabolic dz:

  • alpha galactosidase deficiency
  • X-linked; males severe and females milder
  • neuropathy (pain and paresthesias in extremities)–> may treat with anti-epileptic (diphenylhydantoin)
  • angiokeratomas on skin and mucous membranes
  • cloudy corneas
  • decreased sweating
  • renal and heart failure
  • ERT available and EFFECTIVE
  • eventual dialysis or transplant may be necessary
A

Fabry disease! (a LSD)

67
Q

Name the metabolic dz:

  • arylsulfatase A deficiency (or sometimes, may be caused by defect in associated activator protein if enzyme assay normal)
  • classic finding is white matter on brain MRI (NO seizure activity–> seizure activity goes with grab matter dz)
  • variable age of onset (birth to adulthood– in adulthood, may be mistaken as dementia and go undiagnosed if not worked up)
  • see regression and deterioration, cognitive decline and gait abnormalities, blindness,
  • sulfatide excreted in urine
  • elevated CSF protein
  • decreased nerve conduction
  • NO TREATMENT
A 
Metachromatic leukodystrophy (leuko-- think white matter!)
(An LSD)
68
Q

Name the metabolic dz:

  • galactosylceramide beta-galactosidase deficiency
  • early infantile leukodystrophy, often with gray matter involvement.
  • hypertonicity, irritability in first 6m of life. progress to hypotonia w/severe mental/motor deterioration
  • death by 2 years
  • increased CSF protein
  • NO effective treatment
A

Krabbe disease! (An LSD)

– must distinguish from GM1 gangliosidosis caused by beta-galactosidase def– Krabbe caused by galactosylceramide beta-galactosidase def)

69
Q

What is the MOST common lysosomal storage disease?

A

Gaucher! (1/15 AJ carrier frequency. 1:50,000 overall occurence)

70
Q

Name the metabolic dz:
-beta-glucosidase deficiency
-3 distinct types; Type 1 does not include brain involvement– associated with painless splenomegaly, decreased platelets, anemia, leukopenia, bone pain, AJ form, ERT available.
Type 2 is acute infantile– may present with hydrops on u/s, severe brain involvement (so no ERT), HSM, die by age 2.
Type 3 is juvenile/subacute. aka Norbottnian form. HSM, brain involvement. Death eventually. No ERT.

  • dx by enzyme assay and presence of lipid storage cells in bone marrow…
  • complete or partial splenectomy may be helpful (spleen is a main site of the storage–> causes the platelet count, etc. to go low)
A

Gaucher disease (an LSD)

71
Q

Name the metabolic disease(s):
3 types; A & B most common in AJ w/combined carrier freq of 1/100.
A & B caused by acid sphingomyelinase def–> see sea blue histocytes in foam cells of bone marrow and other tisses. Cherry red spot possible w/ either.
A shows infancy onset, FTT, HSM, rapid neurodegen, death by 2-3
B shows dx in childhood (more residual enzyme activity), HSM, little neurologic involvement, survive into adulthood, may have progressive pulmonary infiltration.
C is caused by altogether diff. mechanism–> shows normal enzyme activity by abnormal accumulation of LDL cholesterol in lysosome. Late childhood onset, progressive neuro dz (LOTS Of neuro involvement), variable HSM, death in 20’s.

A

Niemann Pick group of disease.

LSD’s

72
Q

Name the metabolic disease(s):

  • Deficiency of one enzyme important to post-translational processing of MANY enzymes results in decreased level of MANY enzyme’s activity.
  • Type II is aka I-cell disease, because INCLUSION bodies may be seen in tissues under microscope. Early death. dysostosis multiplex, MR, hepatomegaly, cardiomegaly, herneas, corneal clouding, claw hand… Bone marrow transplant the only avail. treatment option.
  • Type III may live into 60’s. Phenotypically LOOK like Hurler w/severe contractures, HSM, ID, coarse facies, but less severe course. (means consider Hurler, Hunter, AND this dz together– this is the rarest!)
A

Mucolipidosis (Types II and III reviewed by Dr. N)

LSD’s

73
Q

Name the metabolic dz:

  • caused by deficiency of the hypoxanthine phosphoribosyltransferase 1 enzyme (HPRT) that is important for recycline purines… means purines are just broken down, resulting in high levels of *uric acid (aka hyperuricemia)
  • X-linked recessive (NO affected females)
  • results in gouty arthritis, bladder and kidney stones, dystonia, chorea, ballismus (flailing of the limbs), usually cannot walk, require assistance sitting, use a wheelchair
  • onset 3-6 months with hypotonia and delay
  • MR
  • Behavioral problems- aggression, self-injury (biting,head banging)
A

Lesch-Nyhan (a defect in purine metabolism)

74
Q

Name the metabolic dz:

  • characteristic alopecia (hair loss), skin rash, seizures, hypotonia, feeding difficulties
  • organic aciduria and increased ammonium on labs
  • NO response to biotin supplementation
A

Holocarboxylase synthetase deficiency (a severe Biotin Disorder)

biotin is an important cofactor to many of the body’s enzymatic activities

75
Q

Name the metabolic dz:

  • seizures, ataxia, hypotonia, hearing loss, eczema, alopecia, optic atrophy
  • organic acidemia and lactic acidosis on labs
  • responds to biotin supplementation– very effective treatment!
A

Biotinidase deficiency (can’t recycle biotin– w/ supplementation, all is good!)

Genetic Counseling (14 decks)

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