Metabolism Disorders
Terms
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- adenosine deaminase defic causes
- SCID
- describe mech of SCID
-
B and T cell defic (bubble boy), ATP>>GTP, causing decreased lymph production
(can be due to Adenosine Deaminase defic) - what type of disorder is lesch nyhan
- purine salvage (along with adenosine deaminiase defic/SCID)
- how does lesch nyhan present
- gout, MR, self mutilation
- what enzyme abnormal in lesch nyhan
- HGPRTase causing increased uric acid
- Gly Storage I dz aka
- von Gierke
- Gly Storage II which enzyme is abnormal
- lyso alpha 1,4 glucosidase (called Pompe's)
- Gly Storage III/Cori which enzyme abnormal
- alpha 1,6 glucosidase (debranching)
- Name all glycogen storage dz names and acronym
- von Gierke, Pompe, Cori, McArdle (very poor carb metabolism)
- enzyme defic in mcArdles
- skel mscl gly phophorylase
- alpha ketoacid-dehydrogenase defic in what dz
- maple syrup urine
- alpha ketoacid-dehydrogenase does what
- used in degradation of branched aa
- Name dz and enzyme defic: weak mscl, big heart, bad liver
- Pompe's (Gly II, defic of lyso alpha 1,4 glucosidase
- hypoglycemia, hi glycogen in liver
- von Gierke (Gly I, defic of glu 6 phosphate)
- mechanism of von Gierke
- glu6P enzyme doesn't work so glycogen all stuck in liver
- clinical presentation/signs/symptoms McArdles
- "PCM poor carb metabolism" Painful cramps myoglobinuria with exercise
- clinical presentation/signs/symptoms Hurlers
- severe MR, corneal clouding, skel/gargoylism, HS, respir infxn/obstruction,
- MPS IV clinical presentation
- skel short, pectus carvinatum, atlantoaxial instability (my pt)
- dermatan and heparan sulfate defic causes
- Hurler
- chondroitin6sulfate problem seen in what dz
- MPS IV (Morquio)
- general problem in MPS dz
- lysosomal storage dz in which defic enzymes to breakdown GAGs
- Gly Storage II dz aka
- Pompe
- alpha ketoacid-dehydrogenase defic presents clinically, and its natural history/progression
- maple syrup urine, CNS defect, MR, death
- Hunter clinical presentation, course
- mildler form of Hurler, w/o corneal clouding, presents later w slower progression, but increased aggression
- defic in fabry's
- alpha galactosidaseA
- accumulation in fabry's
- ceramide trihexoside
- clinical presentation fabry's
-
peripheral neuro hands/feet, CVS dz, renal F, angiokeratomas (red/purple skin),
can present just w RF - defic in Krabbe
- b-galactosidase resulting in accum galactocerebroside
- accumulation in krabbe
- galactocerebroside
- clinical presentation krabbe, histol
-
peripheral neuro w spasticity, MR, optic atrophy
histol: globoid cells in degen white matter of brain - defic in nieman pick
- sphingomyelinase
- accum in Nieman Pick
- sphingomyelin
- clinical present Nieman Pick--key difft feature
-
HS, progressive neurodegen, cherry spot
HS key to difft from Tay Sach - prognosis Nieman Pick
- die by 3
- clinical presentation Tay Sach
- progress neurodeg, cherry red spot, lysozymes w onion skin
- lysozymes with onion skin
- Tay Sach
- defic in Tay Sach
- hexosaminidaseA
- accum in Tay Sach
- GM2 ganglioside
- arylsulfatase abnormal in what dz
- Metachrom Leuko Dys
- defic in Metachrom Leuko Dys
- arylsulfataseA
- accum in MLD, and where
- sulfatide (in brain, kidney, liver, peripheral n)
- clinical MLD
- central and peripheral demyelin w ataxia, dementia
- defic in gauchers
- b-glucocerebrosidase
- accum in gauchers
- glucocerebroside
- clinical gaucher
- HS, aseptic necrosis femur, bone crises, gaucher cells
- histol of gaucher cells
- macrophage with crinkled enlarged cytoplasm.
- defic in Hurler
- a-L iduronidase
- defic in Hunter
- iduronate sulfatase
- defic in fruc intolerance
- aldolase B
- defic in esstl fructosemia
- fructokinase
- defic in galactosemia
- gal 1P uridyl trx
- general pathophysio of problem in fruc intolerance
- Fru 1P decreases available phopshate, inhiibiting glycogenolysis and gluconeogenesis
- problem in galactosemia, clinical presentation
- accum of toxins (galacitol) (causing cataracts, HS, MR, +/- jaundice, vomit)
- clinical present of fruc intolerance
- hypogly, jaundice, cirrhosis
- galactokinase defic presents
- galactosemia and uria
- which sugar disorders treatable by diet
- galactosomia, no galactose and no lactose
- problem in G6PD defic
- decr NADPH in RBC to keep glutathione reduced, leads to hemo anemia with oxidative stress
- triggers of hemo anemia in G6PD defic
- fava, sulfonamides, primaquine (latent form malaria), TB Rx
- pathognemonic finding of G6PD (PBS)
- Heinz bodies (ppt of Hb in RBC)
- problem in CGD
- PMN can't phago (no H2O2)
- CGD present
- skin, LN, lung infxn with opp bac, esp Staph, E Coli, Aspergillus--in boys
- LAD clinically presents
- gingiva and skin infection
- problem in LAD
-
PMN,
LAD1=no b2 integrins, LFA
LAD2=no sialyl lewis x - present of Chediak Higashi
- Staph and strep infxns
- problem in Chediak Higashi
- defect phago (microtubules and lysosomes empty)
- problem in PKU
- accum of phenylalanine, Tyr becomes essential
- defici in PKU
- low THF, low phenyl. hydroxylase
- PKU present
- MR, fair skin, exczema, musty odor
- defic in alkaptonuria
- homogentisic acid oxidase (degrades tyr)
- clinical present alkaptonuria
- urine dark on standing, connective tissue dark, ***arthralgia
- tyrosinase defic results in what
- albinism
- problem in albinism
- no tyrosinase, can't make melanin
- homocystinuria defic in
- cytathionine synthase or meth synthase
- clinical present of homocystinuria (besides UA)
- (UA has homocys), MR, osteo, lens dislocate
- defic in cystinuria
- defic tubular aa transporter Cys, Orn, Lys, Arg
- clinical present of cystinuria
- kidney stones (tx acetazolamide which alkalinizes the urine)
- how does sel IgA defic present
- GI, respir infxns, milk allergy, transfusion rxn
- how common is sel IgA and what is it assoc w?
- common, assoc with CVID, autoimmune and allergy
- labs on selIgA, tx?
-
labs: only IgA defic
tx: IV Ig - clinical presentation CVID
- PNA, bronchitis, sinusitis, GI in 15-35yo
- labs in CVID
-
immuniz gives low IgM, no IgG
overall low Ig levels - CVID assoc w
- autoimmune, cancer, selIgA
- clinical present Hyper IgM
- pyogenic infxns, young male
- problem in HyperIgM
- problem CD40L so no IgG switch
- labs in HyperIgM
-
no IgG, IgA,
IgM very high - Bruton's problem?
- arrest in preB cells bc no tyr kinase
- clinical present Brutons
- 6mo male, with PNA, sinusitis, otitis
- labs Brutons
- no Ig, no B cells
- Bruton's also called
- X linked gamma globulin
- tx for Brutons
- NO LIVE vaccines
-
Wiskott Aldrich clinically present
pathophysio of the problem
lab studies -
WIPE Wiskott, Infxns, thrombocytopenic Purpuea, Eczema
can't mount IgM ag encapsulated org
hi IgA, normal IgE, low IgM -
Wiskott Aldrich problem
labs -
no IgM--unable to mount IgM response to encapsulated orgs
labs: hi IgA, normal IgE, low IgM - Ataxia telangiectasia clinical present
- ataxia, spider angiomas
- Problem in Ataxia Telangiectasia, labs
-
problem: DNA repair in response to xray
labs: low IgA - difft Ig defic
-
all Ig=Brutons
IgA=sel IgA or atxia telang
hyperIgM (no CD40)
IgM=Wiskott Aldrich
hyperIgE=Job's - ceramide formed from
-
sphingosine plus fa
(where sphingosine=serine + palmitate) - gangliosides made up of
- ceramide + oligosacc + sialic
- cerebrosides made up of
- ceramide + glucose/galactose
- sphingomyelin made up of
- ceramide + phosphoryl Cl
- ceramide is used in...
-
gangliosides (add oligosacc and sialic)
cerebrosides (add glu/galactose)
sphingomyelin (add phosphoryl chol) - Gardners syndrome
-
SOD (sebaceous cysts, osteomas, desmoid), + polyps SI and colon
(v FAP polyps in rectum and colon) - Peutz Jegher
-
polyps (hamartomas) anywhere GI
buccal pigment, increase likely extra-GI malignancy - Plummer Vinson
- eso web, Fe defic, dysphagia, spoon nails, atrophic oral, RISK SCC
- Turcot syndrome
- colon polyps and CNS tumor
- von Hippel Lindau
-
cystic and Cb hemangioblastomas, angiomalform retina, ??pheo (CCAP)
**50% RCC** - difft polyps in difft parts GI
-
colon/rectum=FAP
anywhere=Peutz Jegher
colon=Turcot
SI/colon=Gardners - NF1
-
cafe au lait
iris hamartomas (Lisch)
axillary freckle
bone
neurofibroma (8% malig) - NF2
-
bilateral acoustic neuroma
note: 50% new mutation - MENI
- Parathyroid, Pancreas, pituitary
- MENIIa
- medullary thyroid (bilat), pheo (bilat), parathyroid hyperplasia
- MENIIb
- medullary thyroid bilat, pheo bilat, muccosal neuromas, marfanoid, constipation (NO PTH)
- Sipples dz aka
- MEN IIa: medullary thyroid (bilat), pheo (bilat), parathyroid hyperplasia
- Osler Rendu Weber
- GI telangiectasia, AV malform
- Waterhouse Friedrichson
- adrenal insuff bc hemorrhage bc meningo