Metabolic and Nutritional

Question 1

What is the gene and inheritance pattern in acrodermatitis enteropathica?

Answer 1

SLC39A4 (intenstinal zinc-specific transporter ZIP4)

Question 2

When can zinc deficiency be seen in infants?

Answer 2

Breastfed infants in mothers w/ low zinc levels or preterm infants as they have lower zinc stores, so when they are weaned off of breastmilk

Question 3

Which has more zinc, breastmilk or formula?

Answer 3

There is more zinc absorption that occurs in breast milk than in formula

This is important because the presentation of inherited zinc malabsorption may be delayed until the infant is weaned off of breastmilk

Question 4

What is the triad seen in acrodermatitis enteropathica?

Answer 4

Erosive vesiculopustular eczematous lesions involving the diaper area, face (periorificial especially) and acral areas

• Also have diarrhea and alopecia

Question 5

Systemic sx’s seen in acrodermatitis enteropathica?

Answer 5

Severe irritability, failure to thrive, photophobia, stomatitis/glossitis/perleche, and nail dystrophy

Question 6

What is the histology seen in acrodermatitis enteropathica?

Answer 6

The cytoplasmic pallor of keratinocytes in the upper epidermis, ballooning and reticular degeneration, necrosis of keratinocytes

• In later lessons you can see parakeratosis, psoriasiform epidermal hyperplasia and the epidermal pallor can be lost

Question 7

What are the lab abnormalities seen in acrodermatitis enteropathica?

Answer 7

Decreased serum zinc (<70 ug/dL), decreased serum alkaline phosphatase (it is zinc-dependent)

Question 8

What is the treatment for acrodermatitis enteropathica?

Answer 8

Life-long zinc sulfate supplementation

resolves quickly with this

Question 9

What causes the biotinidase deficiency and holocarboxylase sythetase deficiency?

Answer 9

Biotinidase deficiency: AR caused by mutations in BTD

Holocarboxylase synthetase deficiency: AR, mutations in HLCS

Question 10

What is the prognosis of biotinidase deficiency and holocarboxylase sythetase deficiency?

Answer 10

Holocarboxylase synthetase deficiency is fatal if untreated and presents earlier (infancy)

Question 11

What are the cutaneous manifestations of biotinidase deficiency and holocarboxylase synthetase deficiency?

Answer 11

Perioral/generalized dermatitis and alopecia

Question 12

What are the extracutaneous manifestations seen in biotinidase deficiency and holocarboxylase synthetase deficiency?

Answer 12

Seizures, developmental delay, hypotonia/ataxia, respiratory issues, vomiting, diarrhea, metabolic ketoacidosis, hepatosplenomegaly sensorineural hearing loss, conjunctivitis and optic atrophy (BTD deficiency) and organic aciduria

Question 13

What is the treatment for biotinidase deficiency and holocarboxylase synthetase deficiency?

Answer 13

IV biotin (if they have the holocarboxylase synthetase deficiency then the dose needs to be higher)

Question 14

What is the gene involved and the inheritance pattern of Hartnup disease?

Answer 14

SLC6A19, AR disorder

Question 15

What is the pathogenesis of Hartnup disease?

Answer 15

Decreased absorption of tryptophan from the GI tract and failure to resorb amino acids in the renal tubules

• Decreased tryptophan leads to decreased nicotinic acid and pellagra-like sx’s (photosensitivity)

Question 16

What is the clinical findings of Hartnup disease?

Answer 16

Presents in childhood w/ acute photodermatitis w/ erythema, blistering, scaling, crusting, and scarring occurring after sun exposure in sun-exposed areas of the face, neck, arms, dorsal hands, wrists, and lower legs

Also can see atrophic glossitis, angular stomatitis, vulvogaginitis, hair loss/fragility, and longitudinal nail streaks

• If untreated can progress to neuro signs (cerebellar ataxia, seizures, intellectual disability, and emotional lability/psychosis

Question 17

Treatment of Hartnup disease?

Answer 17

Oral nicotinamide supplementation

Question 18

What is the gene and inheritance of phenylketonuria?

Answer 18

AR disorder 2/2 loss of function mutation in phenylalanine hydroxylase (PAH gene) –> inability to convert phenylalanine to tryptophan

Question 19

What are the cutaneous manifestations of phenylketonuria?

Answer 19

Diffuse hypopigmentation w/ blonde hair, blue eyes, eczematous dermatitis, photosensitivity, and sclerodermatous changes of the torso and thighs

Question 20

Systemic sx’s in phenylketonuria?

Answer 20

Mousy odor of urine, short stature, microcephaly, mental retardation, seizures, irritability, psychosis, etc (neuro sx’s)

Question 21

Why is hypopigmentation seen in phenylketonuria?

Answer 21

Inhibitory effect of increases phenylalanine on tyrosinase

Question 22

Treatment for phenylketonuria?

Answer 22

Low phenylalanine diet

avoid aspartame

Question 23

What is the gene and mode of inheritance for homocystinuria?

Answer 23

AR disorder –> deficiency of cystathionine beta-synthetase (CBS)

leads to increased homocysteine

Question 24

What are the cutaneous manifestations in homocystinuria?

Answer 24

Hypopigmentation of skin and hair, brittle hair, malar erythema, livedo reticularis, and leg ulcers

Question 25

What are some systemic findings in homocystinuria?

Answer 25

Ectopia lentis (downward displacement of lens), seizures, metal retardation, marfanoid habitus, metiral valve prolapse, cardiovascular and cerebrovascular events (thromboembolic events), VTE

Question 26

What is the gene and inheritance of Lesch-Nyhan syndrome?

Answer 26

XLR disorder secondary to hypoxanthine-guanine phosphoribosyltransferase mutation (HGPRT)

Question 27

What are the main findings in Lesch-Nyhan syndrome?

Answer 27

Orange uric acid crystals in the diaper

• Intellectual impairment
• Signifcant self-mutilation
• Uric acid nephropathy, gout

Question 28

What is the inheritance and the gene involved in Prolidase deficiency?

Answer 28

AR disorder 2/2 mutations in peptidase D (PEPD)

Question 29

What are the cutaneous findings in Prolidase deficiency?

Answer 29

Severe, progressive ulcerations of the lower extremities, diffuse telangiectasias, photosensitivity, impetigo-like dermatitis, and eczematous dermatitis

• The ulcers are chronic and do not respond well to treatment
• Recurrent infections contribute to morbidity and mortality

Question 30

What facial features can be seen in prolidase deficiency?

Answer 30

Hypertelorism, ptosis/beaked nose/ frontal bossing

Question 31

What is the gene and inheritance pattern seen in Alagille syndrome?

Answer 31

Jagged 1 (JAG1) gene

• AD

Question 32

Skin findings in Alagille syndrome?

Answer 32

Triangular facies w/ broad forehead, hypertelorism, deep-set eyes, large ears, sharply pointed chin

• Tuberous xanthomas, hypercholesterolemia, and hypertriglyceridemia
• congenital intrahepatic biliary hypoplasia

Question 33

What is the inheritance and gene mutation in Hunter syndrome?

Answer 33

XLR IDS gene (encodes lysosomal enzyme iduronate 2-sulfatase)

• Mutations lead to accumulation of glycosaminoglycans in almost all organs and tissues

Question 34

What are the cutaneous findings in Hunter syndrome?

Answer 34

Hypertrichosis, coarse facies (thick nose, thick lips, and tongue), pebbled ivory-colored plaques between scapulae on upper back, as well as upper arms/thighs

Question 35

What is the difference between Hunter syndrome and Hurler Syndrome cutaneous findings-wise?

Answer 35

Hurler syndrome has dermal melanosis, mental retardation and “gargoyle” appearance, but otherwise as the hypertrichosis and coarse facies

Question 36

What is the histology in Hunter syndrome?

Answer 36

Increased mucin in the mid and lower dermis

There are metachromatic granules in the cytoplasm of fibroblasts and sometimes eccrine sweat glands

Question 37

Systemic findings in Hunter syndrome?

Answer 37

Cardiomyopathy, hepatosplenomegaly, skeletal deformities, short stature, neurodegeneration, papilledema, retinal pigmentation, and hoarse voice

Question 38

What is the gene and mutation in Alkaptonuria?

Answer 38

AR disorder secondary to a mutation in homogentisate 1,2-dioxygenase gene (HGO)

Question 39

What are the cutaneous findings in Alkaptonuria?

Answer 39

Blue-grey pigmentation (ochronosis) on the face, nose, ears (seen well in cartilage), and sclera

Question 40

Systemic findings in alkaptonuria?

Answer 40

Dark sweat, cerumen, and urine (pH>7.0; when you add NaOH to urine –> darkening)

• Mitral/aortic valvulitis –> increased MI risk
• Intervertebral disc calcification –> severe arthritis