Metabolic and Nutritional Flashcards
What is the gene and inheritance pattern in acrodermatitis enteropathica?
SLC39A4 (intenstinal zinc-specific transporter ZIP4)
When can zinc deficiency be seen in infants?
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
Which has more zinc, breastmilk or formula?
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
What is the triad seen in acrodermatitis enteropathica?
Erosive vesiculopustular eczematous lesions involving the diaper area, face (periorificial especially) and acral areas
- Also have diarrhea and alopecia
Systemic sx’s seen in acrodermatitis enteropathica?
Severe irritability, failure to thrive, photophobia, stomatitis/glossitis/perleche, and nail dystrophy
What is the histology seen in acrodermatitis enteropathica?
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
What are the lab abnormalities seen in acrodermatitis enteropathica?
Decreased serum zinc (<70 ug/dL), decreased serum alkaline phosphatase (it is zinc-dependent)
What is the treatment for acrodermatitis enteropathica?
Life-long zinc sulfate supplementation
resolves quickly with this
What causes the biotinidase deficiency and holocarboxylase sythetase deficiency?
Biotinidase deficiency: AR caused by mutations in BTD
Holocarboxylase synthetase deficiency: AR, mutations in HLCS
What is the prognosis of biotinidase deficiency and holocarboxylase sythetase deficiency?
Holocarboxylase synthetase deficiency is fatal if untreated and presents earlier (infancy)
What are the cutaneous manifestations of biotinidase deficiency and holocarboxylase synthetase deficiency?
Perioral/generalized dermatitis and alopecia
What are the extracutaneous manifestations seen in biotinidase deficiency and holocarboxylase synthetase deficiency?
Seizures, developmental delay, hypotonia/ataxia, respiratory issues, vomiting, diarrhea, metabolic ketoacidosis, hepatosplenomegaly sensorineural hearing loss, conjunctivitis and optic atrophy (BTD deficiency) and organic aciduria
What is the treatment for biotinidase deficiency and holocarboxylase synthetase deficiency?
IV biotin (if they have the holocarboxylase synthetase deficiency then the dose needs to be higher)
What is the gene involved and the inheritance pattern of Hartnup disease?
SLC6A19, AR disorder
What is the pathogenesis of Hartnup disease?
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)
What is the clinical findings of Hartnup disease?
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
Treatment of Hartnup disease?
Oral nicotinamide supplementation
What is the gene and inheritance of phenylketonuria?
AR disorder 2/2 loss of function mutation in phenylalanine hydroxylase (PAH gene) –> inability to convert phenylalanine to tryptophan
What are the cutaneous manifestations of phenylketonuria?
Diffuse hypopigmentation w/ blonde hair, blue eyes, eczematous dermatitis, photosensitivity, and sclerodermatous changes of the torso and thighs
Systemic sx’s in phenylketonuria?
Mousy odor of urine, short stature, microcephaly, mental retardation, seizures, irritability, psychosis, etc (neuro sx’s)
Why is hypopigmentation seen in phenylketonuria?
Inhibitory effect of increases phenylalanine on tyrosinase
Treatment for phenylketonuria?
Low phenylalanine diet
avoid aspartame
What is the gene and mode of inheritance for homocystinuria?
AR disorder –> deficiency of cystathionine beta-synthetase (CBS)
leads to increased homocysteine
What are the cutaneous manifestations in homocystinuria?
Hypopigmentation of skin and hair, brittle hair, malar erythema, livedo reticularis, and leg ulcers
What are some systemic findings in homocystinuria?
Ectopia lentis (downward displacement of lens), seizures, metal retardation, marfanoid habitus, metiral valve prolapse, cardiovascular and cerebrovascular events (thromboembolic events), VTE
What is the gene and inheritance of Lesch-Nyhan syndrome?
XLR disorder secondary to hypoxanthine-guanine phosphoribosyltransferase mutation (HGPRT)
What are the main findings in Lesch-Nyhan syndrome?
Orange uric acid crystals in the diaper
- Intellectual impairment
- Signifcant self-mutilation
- Uric acid nephropathy, gout
What is the inheritance and the gene involved in Prolidase deficiency?
AR disorder 2/2 mutations in peptidase D (PEPD)
What are the cutaneous findings in Prolidase deficiency?
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
What facial features can be seen in prolidase deficiency?
Hypertelorism, ptosis/beaked nose/ frontal bossing
What is the gene and inheritance pattern seen in Alagille syndrome?
Jagged 1 (JAG1) gene
- AD
Skin findings in Alagille syndrome?
Triangular facies w/ broad forehead, hypertelorism, deep-set eyes, large ears, sharply pointed chin
- Tuberous xanthomas, hypercholesterolemia, and hypertriglyceridemia
- congenital intrahepatic biliary hypoplasia
What is the inheritance and gene mutation in Hunter syndrome?
XLR IDS gene (encodes lysosomal enzyme iduronate 2-sulfatase)
- Mutations lead to accumulation of glycosaminoglycans in almost all organs and tissues
What are the cutaneous findings in Hunter syndrome?
Hypertrichosis, coarse facies (thick nose, thick lips, and tongue), pebbled ivory-colored plaques between scapulae on upper back, as well as upper arms/thighs
What is the difference between Hunter syndrome and Hurler Syndrome cutaneous findings-wise?
Hurler syndrome has dermal melanosis, mental retardation and “gargoyle” appearance, but otherwise as the hypertrichosis and coarse facies
What is the histology in Hunter syndrome?
Increased mucin in the mid and lower dermis
There are metachromatic granules in the cytoplasm of fibroblasts and sometimes eccrine sweat glands
Systemic findings in Hunter syndrome?
Cardiomyopathy, hepatosplenomegaly, skeletal deformities, short stature, neurodegeneration, papilledema, retinal pigmentation, and hoarse voice
What is the gene and mutation in Alkaptonuria?
AR disorder secondary to a mutation in homogentisate 1,2-dioxygenase gene (HGO)
What are the cutaneous findings in Alkaptonuria?
Blue-grey pigmentation (ochronosis) on the face, nose, ears (seen well in cartilage), and sclera
Systemic findings in alkaptonuria?
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
