Rare Inherited Diseases Flashcards by Isabelle Houston

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Alkaptonuria

AR; homogentisate oxidase deficiency → homogentisic acid buildup; ochronosis, dark urine, arthritis

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Friedreich Ataxia

AR; GAA repeat (FXN gene); spinocerebellar & dorsal column degeneration, kyphoscoliosis, diabetes, hypertrophic cardiomyopathy

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Lesch-Nyhan Syndrome

X-linked recessive; HGPRT deficiency → purine salvage defect; self-mutilation, gout, dystonia, intellectual disability

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Metachromatic Leukodystrophy

AR; Arylsulfatase A deficiency → sulfatide accumulation; demyelination, ataxia, dementia

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Zellweger Syndrome

AR; Peroxisome biogenesis disorder (PEX genes); hypotonia, seizures, hepatomegaly, early death

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Hartnup Disease

AR; Neutral amino acid transporter defect → niacin deficiency; pellagra-like symptoms (diarrhea, dermatitis, dementia)

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Menkes Disease

X-linked recessive; ATP7A mutation → impaired Cu absorption; brittle hair, hypotonia, neurodegeneration

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Adrenoleukodystrophy

X-linked recessive; ABCD1 mutation → VLCFA accumulation in CNS & adrenals; progressive neurodegeneration, adrenal insufficiency

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Kartagener Syndrome

AR; Dynein arm defect → ciliary dysfunction; situs inversus, chronic sinusitis, infertility

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Alpha-1 Antitrypsin Deficiency

Codominant; misfolded A1AT → lung & liver disease; panacinar emphysema, cirrhosis, PAS+ globules in liver

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Chediak-Higashi Syndrome

AR; LYST mutation → microtubule dysfunction; albinism, recurrent infections, giant granules in neutrophils

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Fabry Disease

X-linked recessive; α-galactosidase A deficiency → Gb3 buildup; episodic neuropathy, angiokeratomas, renal failure

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Canavan Disease

AR; ASPA mutation → N-acetylaspartate buildup; hypotonia, megalencephaly, spongy degeneration of white matter

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Gaucher Disease

AR; Glucocerebrosidase deficiency → lipid-laden macrophages; hepatosplenomegaly, pancytopenia, bone crises

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Niemann-Pick Disease

AR; Sphingomyelinase deficiency → foam cells, cherry-red macula; neurodegeneration, hepatosplenomegaly

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Pompe Disease

AR; α-1,4-glucosidase deficiency → glycogen buildup in lysosomes; cardiomyopathy, hypotonia, exercise intolerance

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Hunter Syndrome

X-linked recessive; Iduronate-2-sulfatase deficiency → GAG buildup; coarse facies, hepatosplenomegaly, developmental delay (no corneal clouding)

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Hurler Syndrome

AR; α-L-iduronidase deficiency → GAG buildup; coarse facies, corneal clouding, hepatosplenomegaly

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Refsum Disease

AR; Phytanoyl-CoA hydroxylase deficiency → phytanic acid buildup; scaly skin, ataxia, cataracts, 4th toe shortening

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Tyrosinemia Type I

AR; Fumarylacetoacetate hydrolase deficiency → succinylacetone buildup; liver failure, renal dysfunction, cabbage-smelling urine

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Prader-Willi Syndrome

Imprinting disorder; paternal deletion (15q11-q13) or maternal UPD; hyperphagia, obesity, hypotonia, intellectual disability

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Angelman Syndrome

Imprinting disorder; maternal deletion (15q11-q13) or paternal UPD; inappropriate laughter, seizures, ataxia

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Fragile X Syndrome

X-linked dominant; CGG repeat expansion (FMR1 gene); intellectual disability, large ears, macroorchidism, mitral valve prolapse

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McCune-Albright Syndrome

Sporadic; GNAS mutation (mosaic); café-au-lait spots, polyostotic fibrous dysplasia, endocrinopathies

Williams Syndrome

Microdeletion of 7q (ELN gene); elfin facies, supravalvular aortic stenosis, hypercalcemia, extreme friendliness

DiGeorge Syndrome

22q11.2 deletion; defective neural crest migration; CATCH-22: Conotruncal defects, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia

Wiskott-Aldrich Syndrome

X-linked recessive; WAS gene mutation; thrombocytopenia, eczema, recurrent infections

Ataxia-Telangiectasia

AR; ATM gene mutation; cerebellar ataxia, oculocutaneous telangiectasias, increased cancer risk

Rett Syndrome

X-linked dominant (MECP2 mutation); neurodevelopmental regression, hand-wringing, microcephaly (affects girls)

Alport Syndrome

X-linked dominant; COL4A5 mutation; progressive renal failure, hearing loss, ocular abnormalities

What is the inheritance pattern and defect in Phenylketonuria?

Autosomal recessive, phenylalanine hydroxylase deficiency

What are the clinical features of Phenylketonuria?

Intellectual disability, seizures, eczema, musty body odor

How is Phenylketonuria diagnosed?

Elevated phenylalanine levels in blood

What is the management for Phenylketonuria?

Low-phenylalanine diet, avoid aspartame

What is the inheritance pattern and defect in Galactosemia?

Autosomal recessive, galactose-1-phosphate uridyltransferase (GALT) deficiency

What are the clinical features of Galactosemia?

Failure to thrive, hepatomegaly, cataracts, intellectual disability

How is Galactosemia diagnosed?

Elevated galactose-1-phosphate levels

What is the management for Galactosemia?

Eliminate galactose from diet (no milk or dairy)

What is the inheritance pattern and defect in Cystic Fibrosis?

Autosomal recessive, CFTR gene mutation (usually delta-F508)

What are the clinical features of Cystic Fibrosis?

Chronic lung infections, pancreatic insufficiency, infertility in males, salty skin

How is Cystic Fibrosis diagnosed?

Sweat chloride test >60 mEq/L, genetic testing

What is the management for Cystic Fibrosis?

Airway clearance therapies, pancreatic enzyme replacement, CFTR modulators (e.g., ivacaftor)

What is the inheritance pattern and defect in Maple Syrup Urine Disease?

Autosomal recessive, branched-chain alpha-keto acid dehydrogenase deficiency

What are the clinical features of Maple Syrup Urine Disease?

Vomiting, poor feeding, lethargy, maple syrup smell in urine

How is Maple Syrup Urine Disease diagnosed?

Elevated branched-chain amino acids (leucine, isoleucine, valine)

What is the management for Maple Syrup Urine Disease?

Restrict branched-chain amino acids in the diet

What is the inheritance pattern and defect in Tay-Sachs Disease?

Autosomal recessive, hexosaminidase A deficiency

What are the clinical features of Tay-Sachs Disease?

Cherry-red spot on the macula, progressive neurodegeneration, hypotonia, developmental delay

How is Tay-Sachs Disease diagnosed?

Hexosaminidase A activity decreased in serum

What is the inheritance pattern and defect in Hurler Syndrome?

Autosomal recessive, alpha-L-iduronidase deficiency

What are the clinical features of Hurler Syndrome?

Gargoylism, coarse facial features, hepatosplenomegaly, developmental delay

How is Hurler Syndrome diagnosed?

Elevated urine glycosaminoglycans (GAGs), enzyme assay

What is the management for Hurler Syndrome?

Bone marrow transplant, enzyme replacement therapy

What is the inheritance pattern and defect in Lesch-Nyhan Syndrome?

X-linked recessive, HGPRT deficiency

What are the clinical features of Lesch-Nyhan Syndrome?

Self-mutilating behaviors (biting lips/fingers), hyperuricemia (gout, kidney stones), choreoathetosis

How is Lesch-Nyhan Syndrome diagnosed?

Elevated uric acid levels, absent HGPRT activity

What is the management for Lesch-Nyhan Syndrome?

Allopurinol for gout management

What is the inheritance pattern and defect in Niemann-Pick Disease?

Autosomal recessive, sphingomyelinase deficiency

What are the clinical features of Niemann-Pick Disease?

Progressive neurodegeneration, hepatosplenomegaly, 'cherry-red' spot on the macula

How is Niemann-Pick Disease diagnosed?

Elevated sphingomyelin levels in serum, deficient sphingomyelinase activity

What is the inheritance pattern and defect in Krabbe Disease?

Autosomal recessive, galactocerebrosidase deficiency

What are the clinical features of Krabbe Disease?

Progressive loss of motor skills, optic atrophy, irritability

How is Krabbe Disease diagnosed?

Elevated galactocerebroside in urine, enzyme assay

What is the inheritance pattern and defect in Gaucher Disease?

Autosomal recessive, glucocerebrosidase deficiency

What are the clinical features of Gaucher Disease?

Hepatosplenomegaly, anemia, thrombocytopenia, bone pain, 'Erlenmeyer flask' deformity

How is Gaucher Disease diagnosed?

Increased glucocerebroside in macrophages (seen on biopsy)

What is the management for Gaucher Disease?

Enzyme replacement therapy (e.g., imiglucerase)

What heritable disease type is associated with genetic anticipation?

Trinucleotide repeat expansion

What are the trinucleotide repeat expansion diseases to know?

Huntington, Myotonic Dystrophy, fragile X, and freidrich ataxia MYO-my! FRIEDRICH was FRAGILE on the HUNT for trinuclotide truffels!

Trinucleotide repeat expansion disease that leads to the caudate hacing decreased Ach and GABA

Huntington

Giant gonads, low set ears

fragile X

FMR1 gene with hypermethylation of cytosine residues

fragile x

MECP2 on X chromosome

Rett syndrome, she RETTurned to her younger self at the MECca

congenital deletion on the short arm of chromosome 5

cri du chat

congential microdeletion of long arm of chromosome 7