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Med 16-17 > Metabolic Disorders > Flashcards

Metabolic Disorders Flashcards

1
Q

What skeletal defects are you most worried about in a child with mucopolysaccharidosis Type I (Hurler Syndrome)?

A

Atlantoaxial Subluxation

With MPS Type 1, skeletal growth is usually normal during the 1st year of life, but severe growth retardation soon develops. These kids are at high risk for atlantoaxial subluxation.

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2
Q

Lack of the phenylalanine hydroxylase enzyme in phenylketonuria prevents the conversion process of what amino acid?

A

Phenylalanine to Tyrosine

Without phenylalanine hydroxylase, phenylalanine cannot be converted into tyrosine. This results in a large, toxic buildup of phenylalanine in both the blood and CNS.

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3
Q

A child is normal at birth. By 2-years of age, he presents with:

  • Coarsened facial features
  • Midface hypoplasia
  • Large tongue
  • Frequent URIs
  • History of inguinal and umbilical hernias
  • Head circumference is > 95th percentile
  • Obstructive sleep apnea
  • Hepatosplenomegaly
  • Corneal clouding
  • Deafness

What is the most likely diagnosis?

A

Mucopolysaccharidosis Type I (Hurler Syndrome)

MPS Type 1 is due to a defect in the gene coding for α-L-iduronidase on chromosome 4p16.3. There is a wide variation in disease presentations. Those severely affected are diagnosed in the first 2 years of life. Those less severely affected are often not diagnosed until early adulthood. They present with bone abnormalities (spondylolisthesis of L5/S1, degenerative bone loss) or eye problems (corneal clouding and retinal disease).

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4
Q

Which mucopolysaccharidosis has disproportionate involvement of the CNS compared to the rest of the body?

A

Mucopolysaccharidosis Type III (Sanfilippo Syndrome)

MPS Type 3 is usually diagnosed at ~ 4–5 years of age, with severe CNS involvement. This disproportionate CNS involvement is unique among the MPSs. Type 3 results from the inability to catabolize heparan sulfate.

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5
Q

What is the most common lysosomal storage disease?

A

Gaucher Disease Type I

Gaucher disease Type 1 is due to a deficiency of lysosomal glucocerebrosidase. This is a non-CNS disease with splenomegaly as the most common presentation. Ashkenazi Jews have a carrier rate of 1/15.

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6
Q

What disorder occurs in 1-2% of the population and presents as muscle weakness and cramping following vigorous exercise?

A

Adenylate Deaminase Deficiency

Adenylate deaminase deficiency is an autosomal recessive–transmitted disease that actually occurs in 1–2% of the population! Serum CK may be increased, but myoglobinuria is not present. Muscle biopsy is normal. Many with the deficiency are asymptomatic.

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7
Q

An infant is normal at birth, but by 3-5 days of life, begins to have feeding difficulties, irregular respirations, and loss of the Moro reflex. A tonic-clonic seizure is noted and prompts the family to bring in the child. You note a sweet smell from the child.

What is the most likely diagnosis?

A

Maple Syrup Urine Disease

Classic MSUD presents with CNS disease early in infancy, and the urine (or hair or skin) smells like maple syrup. Infants are well at birth but start having symptoms by 3–5 days of life, with rapid progression to death in 2–4 weeks without treatment. They cannot catabolize the branched-chain amino acids. Thus, they have increased plasma and urine levels of valine, leucine, and isoleucine. Finding alloisoleucine, an abnormal amino acid, is diagnostic.

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8
Q

Most cases of this disorder occur in children between 3 and 5 years of age with:

  • Ataxia
  • Dysphagia
  • Supranuclear, vertical-gaze palsy (downward, upward, or both) - i.e., voluntary, vertical eye movement is lost
  • Involuntary, reflex “doll’s eye” movements are preserved
  • Hepatosplenomegaly
  • With an emotional scare, cataplexy (sudden loss of motor movement) can occur
  • Narcoplexy is common

Other children (6-12 years) will present with poor school performance and impaired fine motor skills.

What is the most likely diagnosis?

A

Niemann-Pick Disease Type C

NPD Type C is the most common form of NPD and occurs in 250–500 children (1/150,000) each year in the U.S. It occurs when cholesterol accumulates within the lysosomes of the reticuloendothelial system, resulting in a secondary buildup of GM2 gangliosidosis.

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9
Q

What does this triad indicate the presence of?

  • Ptosis
  • Opthalmoplegia
  • Ragged-red fiber myopathy
A

Kearns-Sayre Syndrome and Chronic Progressive External Ophthalmoplegia (CPEO) Syndromes

Kearns-Sayre is the most severe of these syndromes and can begin in infancy, childhood, or adolescence. In addition to the triad, multisystem disease is common, particularly:

  • Cardiomyopathies
  • Diabetes mellitus
  • Cerebellar ataxia
  • Deafness

The CPEO syndromes are less severe and present later in life.

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10
Q

An infant presents with:

  • Vomiting
  • Jaundice
  • Hepatosplenomegaly
  • Hypoglycemia
  • Seizure
  • Poor weight gain
  • Cataracts
  • Vitreous hemorrhage
  • Ascites
  • Reducing substance is in the urine

What is the most likely diagnosis?

A

Galactose 1-Phosphate Uridyl Transferase (GALT) Deficiency (Galactosemia)

Galactosemia classically presents in infancy with some combination of these findings. The infant cannot metabolize galactose 1-phosphate, and this accumulates in the kidney, liver, and brain. Removing galactose from the diet reverses growth failure and renal/hepatic problems. Even the cataracts will regress!

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11
Q

You are following a male patient with the following progression:

  • He is normal at birth
  • By age 3-6 months, he has FTT, emesis, and irritability
  • By age 2-3 years, he displays tendency to self-mutilate with biting of his lips and fingers

What is the most likely diagnosis?

A

Lesch-Nyhan Disease (Hypoxanthine Guanine Phosphoribosyltransferase [HGPRT] Deficiency)

Lesch-Nyhan disease (HGPRT deficiency) is an X-linked recessive (boys only) disorder. The HGPRT enzyme preserves hypoxanthine and guanine, and then converts them to nucleotides. Absence of the enzyme results in the neurologic defects, and there is a huge increase in uric acid production, resulting in gout and renal stones.

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12
Q

Name the metabolic disease that can cause subdural hematomas and retinal hemorrhages, which can be mistaken for child abuse?

A

Glutaric Aciduria Type I

Glutaric aciduria Type 1 is an autosomal recessive enzyme defect (lack of glutaryl-CoA dehydrogenase) in the catabolic pathway of lysine, hydroxylysine, and tryptophan.

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13
Q

A child presents with presumed mucopolysaccharidosis. His disease is X-linked recessive and there is no corneal clouding.

What type of mucopolysaccharidosis does he have?

A

Mucopolysaccharidosis Type II (Hunter Syndrome)

MPS Type 2 is X-linked (only males display the trait [except for the rare affected female patient with Turner syndrome]) and does not have corneal clouding. Remember, you have to see well to be able to “hunt.” Hunter’s = no corneal clouding. Atlantoaxial instability is not as common in Type 2 as in Type 1.

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14
Q

What is a late complication of propionic acidemia?

A

Cardiomyopathy

Propionic acidemia presents in the early neonatal period with severe ketoacidosis. The infant will have encephalopathy, vomiting, and bone marrow depression. Cardiomyopathy is a late complication.

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15
Q

A patient presents with:

  • Elevated plasma ammonia
  • Low BUN
  • Respiratory alkalosis

What general class of metabolic disorders is the most likely diagnosis?

A

Urea Cycle Defect

The key with urea cycle defects is the finding of elevated ammonia with a respiratory alkalosis (not a metabolic acidosis, as would be expected with sepsis or other metabolic disorders). The most common defect is ornithine transcarbamylase deficiency (OTC), which is also one of the few X-linked recessive metabolic conditions. (All other urea cycle defects have autosomal recessive inheritance.)

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16
Q

Name the disorder with these findings:

  • Hypoactive or absent deep tendon reflexes
  • Ataxia
  • Corticospinal tract dysfunction
  • Impaired vibratory and proprioceptive function
  • Hypertrophic cardiomyopathy
  • Diabetes Mellitus
A

Friedrich Ataxia

It is an AR disorder and is mapped to chromosome 9. It occurs in about 1/50,000.

17
Q

An 18-year-old presents with:

  • Exercise-induced muscle cramps
  • Increasing exercise intolerance
  • Burgundy-colored urine after exercise
  • CK that is elevated at rest and increases after exercise
  • Elevated ammonia, instead of elevated lactate (as would normally be expected), after exercise

What is the most likely diagnosis?

A

Type 5 Glycogen Storage Disease (GSD),

a.k.a. McArdle Disease

The key with Type 5 GSD is the elevated CK at rest and the elevated ammonia after exercise. Exercise will also increase uric acid in the blood. This is an autosomal recessive disorder. The muscle phosphorylase deficiency causes reduced ATP generation by glycogenolysis, resulting in glycogen accumulation.

18
Q

Menkes disease (Kinky hair disease) is caused by impaired uptake of what mineral?

A

Copper

Menkes disease is a rare X-linked recessive disease (boys only) due to a mutation in the Menkes (ATP7A) gene, which causes impaired uptake of copper. It occurs in about 1/50,000 to 1/250,000 births. Partial deficiency of the enzyme dopamine-ß-hydroxylase is a hallmark of Menkes disease.

19
Q

Name the 3 branched-chain amino acids.

A

Valine, Leucine, Isoleucine

Problems metabolizing these 3 can cause organic acid intermediates to accumulate, resulting in toxic effects. Look (smell, actually) for a strange urine odor. Autosomal recessive inheritance is most common for these defects.

20
Q

A 3½-month-old presents with:

  • “Doll-like face with fat cheeks”
  • Thin extremities, short stature, and large protuberant abdomen
  • Hepatomegaly
  • Hypoglycemia with seizures
  • Lactic acidosis
  • Hyperuricemia
  • Hyperlipidemia—increased VLDL, LDL, and apolipoproteins B, C, and E
  • Normal AST and ALT
  • Plasma that appears milky

What is the most likely diagnosis?

A

Type I Glycogen Storage Disease (Von Gierke disease)

Type 1 GSD is due to a defect in glucose-6-phosphatase in the liver, kidney, and intestinal mucosa. There are 2 subtypes: Type 1a is due to a defect in the enzyme, Type 1b is due to a defect in the translocase that transports the enzyme across the cell membrane. Affected individuals suffer from severe and rapid fasting hypoglycemia; therefore, the babies present when they start to skip a feeding during the night.

21
Q

What infection are children with galactosemia at greater risk of having?

A

E. coli Sepsis

Infants with galactose 1-phosphate uridyl transferase deficiency (galactosemia) are at increased risk of having E. coli sepsis, which commonly precedes the diagnosis of galactosemia!

22
Q

An infant presents at 6 weeks of age with:

  • Enhanced startle reflex to noise or light, with resulting quick extension of the arms and legs with clonic movement (doesn’t diminish with repeated stimuli)
  • Motor skills are progressively lost.
  • Axial hypotonia
  • Extremity hypertonia
  • Hyperreflexia
  • Macrocephaly
  • Auditory stimuli cause the child to seize.
  • Visceral organs are normal.
  • A macular cherry-red spot

What is the most likely diagnosis?

A

Tay-Sachs Disease

Tay-Sachs disease can present in an infantile form (as here) or in the juvenile/adult form, with the latter being more common in Ashkenazi Jews. The adult/juvenile form of the disease progresses slowly. Early in childhood, children with this form are labeled “clumsy and awkward.”

23
Q

A patient presents with:

  • Marfanoid habitus
  • Developmental delays
  • Lens dislocation, which is downward and medial

What is the most likely diagnosis?

A

Homocystinuria

Homocystinuria is an autosomal recessive disorder that causes elevated levels of homocysteine. Do not get homocystinuria confused with Marfan syndrome. In Marfan’s, the patients have a normal IQ and the lens dislocation is upward (upward lens, normal IQ), as opposed to homocystinuria, where the IQ is low and the lens dislocation is downward (downward lens, low IQ).

24
Q

The parents of a 2-week-old are concerned about their child. When they change his diapers, there is often a dark-brown or black pigment in the diaper.

What is the most likely diagnosis?

A

Alkaptonuria

Alkaptonuria is due to deficiency of homogentisate 1,2-dioxygenase, which is the 3rd step in tyrosine metabolism. Fresh urine is normal, but as it “sits” and alkalinizes, the oxidation of homogentisic acid proceeds and a dark-brown/black pigment forms. These children are otherwise asymptomatic. In their 30s, they will start to have pigment deposition in their ears and sclerae called ochronosis. This can lead to ochronosis arthritis, which is the major medical complication of the disorder.

25
Q

What are some complications of propionic acidemia (PA)?

A

Cardiomyopathy, FTT, Recurrent Infections, Pancreatitis

PA presents in the early neonatal period as severe ketoacidosis with or without hyperammonemia. The infant will have encephalopathy, vomiting, and bone marrow depression. Complications include cardiomyopathy, malnutrition with FTT, recurrent infections, and pancreatitis.

26
Q

Mitochondrial inheritance comes from which parent?

A

The Mother

27
Q

An infant presents with encephalopathy and you notice the odor of “sweaty feet.”

What is the most likely diagnosis?

A

Isovaleric Acidemia (IVA)

IVA is an autosomal recessive disorder localized to chromosome 15 and is due to a defect in isovaleryl-CoA dehydrogenase. This is the “sweaty feet odor” intoxication. IVA can present in the newborn period with an acute episode of severe metabolic acidosis and moderate ketosis with vomiting, which can lead to coma and death. More typically, it presents in infancy or childhood and is precipitated by an infection or increased protein intake.

28
Q

Homozygous children with this disorder develop planar xanthomas from birth to 5 years of age. Tendon and tuberous xanthomas occur in children 5-15 years of age.

What is the disorder?

A

Familial Hypercholesterolemia (FH)

FH is autosomal dominant in its transmission. Achilles tendonitis or tenosynovitis may be the 1st clue in a teenager. Angina and symptomatic coronary disease occur in the 2nd decade of life. Serum cholesterol is usually 600–1,000 mg/dL.

29
Q

Which porphyria will present with skin photosensitivity, but without vesicle/bullae formation, and more likely will manifest as angioedema with redness, burning, itching, and swelling with sun exposure?

A

Erythropoietic Protoporphyria (EPP)

EPP is an autosomal dominant disease that is due to partial deficiency of ferrochelatase. This is the most common erythropoietic porphyria, and it is second behind porphyria cutanea tarda (PCT) for all porphyrias. It is the most common porphyria in children. Oral beta-carotene improves tolerance to sunlight.

30
Q

What disease presents with cutaneous photosensitivity and develops fluid-filled vesicles and bullae on the sun-exposed areas of their face, dorsa of the hands and feet, forearms, and legs?

A

Porphyria Cutanea Tarda (PCT)

PCT is the most common of the porphyrias and is caused by a deficiency of hepatic URO-decarboxylase. Usually you can induce complete remission by phlebotomy to reduce hepatic iron. Remove a unit of blood (450 mL) every 1–2 weeks. Typically, remission occurs after 5 or 6 phlebotomies.

31
Q

A Scandinavian girl presents with recurrent abdominal pain with abdominal distention and noticeable decreased bowel sounds. There is no abdominal tenderness or fever. It seems to occur after taking her Bactrim for a UTI (she had complaints of dysuria, but the urine was not tested).

What is the most likely diagnosis?

A

Acute Intermittent Porphyria (AIP)

AIP is an autosomal dominant disorder more commonly seen in Scandinavians and the British. It is due to hydroxymethylbilane synthase deficiency (HMBS). The most common drugs to cause an attack are phenobarbital, sulfonamides, seizure medications, griseofulvin, and OCPs.

32
Q

Mitochondrial inheritance comes from which parent?

A

The Mother

Mitochondrial DNA (mtDNA), and therefore all disorders of mtDNA, are maternally inherited.

33
Q

What is the classic triad of holocarboxylase synthetase or biotinidase deficiency?

A

Alopecia, Skin Rash, Encephalopathy

Seizures, hearing loss, and blindness can also be complications of untreated disease. Multiple carboxylase deficiency is due to either lack of holocarboxylase synthetase or biotinidase. Biotinidase deficiency usually presents later, and has a rash that looks like acrodermatitis enteropathica.

34
Q

A 2-week-old, with noticeably fair hair and skin compared to the parents, was completely normal at birth. The child had a home delivery with no postnatal testing for inborn errors.

Now she has developed these findings:

  • Vomiting
  • Irritability
  • Eczematoid rash
  • “Mousy” or musty odor

What is the most likely diagnosis?

A

Phenylketonuria (PKU)

PKU is an autosomal recessive disorder in which phenylalanine cannot be converted into tyrosine. The enzyme defect is in phenylalanine hydroxylase (PAH). Those who remain untreated have severe intellectual disability (IQ < 30), with irreversible damage by 8 weeks of age. PKU was the first metabolic condition on newborn screening, beginning 50 years ago. Hopefully you will never see this in clinic, but be suspicious if the symptoms fit, especially if the baby was born outside of the U.S.

35
Q

An adolescent boy at the onset of puberty presents with:

  • Severe, episodic pain in the hands and feet
  • Fever
  • Heat exposure sets off the pain crises
  • He does not sweat

What is the most likely diagnosis?

A

Fabry Disease

Fabry disease is the only sphingolipidosis transmitted as an X-linked recessive disease; thus, it mainly affects boys. Confirm the diagnosis by finding deficiency of lysosomal α-galactosidase in plasma, leukocytes, or cultured skin fibroblasts.

36
Q

What defect has cataracts as the only finding (otherwise the infant is completely asymptomatic)?

A

Galactokinase Deficiency

Galactokinase deficiency presents only as cataracts, and the infant is otherwise asymptomatic. The defect is on chromosome 17. Treat with dietary restriction of galactose.

37
Q

An infant is normal at birth but, within several weeks, presents with:

  • Hypotonia and generalized muscle weakness
  • Macroglossia
  • Hepatomegaly
  • CHF due to hypertrophic cardiomyopathy
  • Elevated CPK, AST, and LDH
  • Muscle biopsy shows vacuoles that are full of glycogen on staining

What is the most likely diagnosis?

A

Type 2 Glycogen Storage Disease (GSD),

a.k.a. Pompe Disease

Type 2 GSD is caused by deficiency in the lysosomal acid α-1,4-glucosidase (a.k.a. acid maltase), which is responsible for breaking down glycogen in lysosomal vacuoles. It is an autosomal recessive disorder. This is the infantile-onset presentation, which is the most severe. There is also a juvenile/late childhood form and an adult form.

38
Q

A 1-year-old presents with fasting-induced lethargy and documented hypoglycemia with a seizure. AST and ALT are elevated, as well as CPK. He also has a history of arrhythmias.

What is the most likely diagnosis?

A

Medium-Chain Acyl-CoA Dehydrogenase (MCAD)

MCAD deficiency, the most common β-oxidation defect, typically presents in the first 2 years of life. Diagnose MCAD deficiency by finding elevated C8, C8:1, and C10:1 esters.

Med 16-17 (27 decks)

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