metabolic x 2

Question 1

What are the mutations that lead to the same phenotype as Methylmalonic acid metbolic disease

Answer 1

mut0, mut−, cblA, cblB, and cblD

Question 2

How many 3-Methylglutaconic acidurias are there and what are they?

Answer 2

There are 5: A group of disorders characterised by excretion of 3-methylglutaconic acid.

I is an inborn error of leucine catabolism; 3-methylglutaconyl- CoA hydratase deficiency: slowly progressive leukoencephalopathy (adulthood)

II: barth syndrome: x linked cardiomyopathy, growth retardation, neutropenia, phospholipid metabolism (TAZ gene)

III: costeff syndrome; optic atrophy, extrapyramidal signs, spasticity,

IV - unclassified

V: DCMA syndrome: cardiomyopathy with conduction deficits and nonprogressive cerebellar ataxia

Question 3

What is Canavan disease? and what is the enzyme + gene associated?

Answer 3

A Leukodystrophy. A disorder of Progressive psychomotor retardation, progressive epileptic encephalopathy, macrocephaly, leukodystrophy (particularly subcortical U fibres) optic atrophy, enzyme: Aspartoacylase. Diagnosis: Organic aciduria (Nacetyltaspartic acid) Gene ASPA

Question 4

What role do the sulphur amino acids (methionine and homocysteine) play in metabolism and what are the major diseases?

Answer 4

Sulphur amino acids play a central role in cytosolic methylation transfer required for a range of functions including the synthesis of creatine, choline and adrenaline as well as DNA methylation.
Disorders may be due to primary disorders of cobalamin (Vitb12) or folate metabolism.
- isolated hyperthmethioninaemia
- A-Adenosylhomocysteine hydrolase deficiency
- Methionine synthase deficiency
- Mild hyperhomocysteinaemia
- classical homocystinuria
- Sulphite oxidase deficiency and molybednum cofactor deficiency

Question 5

What are the disorders of Histidine, tryptophan and lysine metabolism and the pathophysiology?

Answer 5

The terminal amino group of lysine is transferred to 2-oxoglutarate (producing glutamatae).
1. glutaric aciduria type I
2. Histidinaemia - no treatment
3. Tryptophanaemia - incidental finding; Tx: nicotinamide
mostly asymptomatic

Question 6

Disorders of Serine, glycine and glycerate metabolism are rare. Describe the biochemistry

Answer 6

Serines: microcephaly, psychomotor retardation, seizures.
Glycine: inability to convert glucose to serine and glycine or to turn NH3 into glucose.tx: L-serine.
1. Non ketotic hyperglycinaemia: severe epileptic encephalopathy, hypotonia, progresive neurological symptoms, neonatal onset; issue with the glycine cleavage system, so can’t use glycine to make glucose
- enzyme studies: lymphocytes, liver.
mutations: GLDC, AMT and GCSH.
-treatment : dextromethorphan (5020mg/day), sodium benzoate aiming to normalise plasma glycine levels; folinic acid. poor prognosis. treat with L-serine

Question 7

what is the physiology of amino acid transport?

Answer 7

several specific transport systems ensure virtually complete (re) absorption of amino acids in the gut and kidneys. The calculation of renal tubular re-absorption shows values >96-99% for most amino acids. Genetic defects of these transport systems are sometimes asymptomatic and are detected only through elevation of the respective amino acids in urine with normal or low levels in plasma. the inability of these systems to work leads to deficiencies and crystallisation in the urine/kidney

Question 8

What is a disorder of amino acid synthetase deficiency?

Answer 8

Glutamine synthetase deficiency: brain malformations, multiple organ failure in neonates, static encephalopathy, recurrent hyperammonaemia

Question 9

What is a common feature of disorders of peptide metabolism?

Answer 9

frequent infections and skin manifestations

• Prolidase deficiency
• Carnosinaemia
• homocarnosinosis

Question 10

What are the 7 major types of disorders of carbohydrate metabolism

Answer 10

1. galactose and fructose
2. gluconeogenesis/glycogenolysid
3. glycogen storage disease
4. glycerol metabolism
5. pentose metabolism
6. glucose transport
7. congenital hyperinsulinism

Question 11

what are the major fx of galactose and fructose metabolic diseases?

Answer 11

inability to intake lactose or fructose. The presence of reducing substances in the urine is an important first clue to the diagnosis.

Question 12

What is hereditary fructose intolerance?

Answer 12

symptoms commence after weaning or supplementary fructose containing food: vomiting, apathy, coma, progressive liver dysfunction, hepatosplenomegaly, hypoglucaemia, rernal tubular dysfunction, FTT, aversion to fructose containing food/sweets
dx: renal tubular damage (increasing glucose, albumin, AA, reducing substnces in urine)

Question 13

What are the symptoms , genetics diagnostic fx and treatment of Galactosaemia

Answer 13

symptoms after start of milk feeds (3rd or 4th day); vomiting, diarrhoea, jaundice, distubrances of liver function (most sensitive reduced IBR), development of bilateral cataracts, sepsis (gram neg organisms), hepatic and renal failure.
enzyme deficiency GALT (galactose-1-phosphate uridyltransferase). varients: Duarte
diagnosis: newborn screening - GALT activity, galactitol, renal tubular damage
Tx: galactose restricted diet throughout life

Question 14

What are the cataracts associated with galactokinase deficiency due to?

Answer 14

build up of galactitol in the lens

Question 15

What are the characteristics of UDP-galactose epimerase deficiency?

Answer 15

like classical galactosaemia

Question 16

What are the disorder of gluconeogenesis?

Answer 16

recurrent hypoglycaemia with lactic acidosis +/- ketosis.
1. Fructose-1, 6 bisphosphatase deficiency (increased lactate, pyruvate, ketones; Tx: oral or IV glucose and insulin.
Phophoenolpyruvate carboxykinase deficiency:

Question 17

Describe glycogen storage disorders

Answer 17

disorders of glycogen degredation, glycolysis, glucose release and glycogen synthesis.
Liver: hypoglycaemia, hepatomegaly, growth retardation (GSD, I, IV, VI, IX 0)
Muscle: exercise intolerance, muscle cramps
mixed/generalised: cardiomyopathy, liver/muscle involvement.

Question 18

What are the disorders of glucose transport?

Answer 18

GLUT1 deficiency; GLUT 2 deficiency, SGLT1 deficiency, SGLT2 deficiency

Question 19

What is Fanconi-Bickel disease

Answer 19

Glycogen storage disease type XI; Glucose transporter 2 (GLUT2 and SLC2A2 gene)
renal fanconi syndrome -> rickets, aminoaciduria, glucosuria, small statue, malabsorption, hepatomegaly, nephromegaly. Fasting hypoglycaemia with no response to glucacon. Tx: frequent feeds

Question 20

Congenital Hyperinsulinsism

Answer 20

neonatal hypoglycaemia: congenital hyperinsulinism due to KATP channel mutations; other disorders assoc. with congenital hyperinsulinism.

Question 21

what disorders are associated with congenital hyperinsulinism?

Answer 21

glucokinase activating mutations
hyperinsulinism-hyperammonaemia syndrome
exercise induced hyperinsulinaemis hypoglucaemia
short chain hydroxacyl-CoA dehydrogenase (SCHAD) deficiency
phosphomannose isomeraase deficiency
Beckwith-Wiedermann syndrome

Question 22

What is the biochemistry of Fatty acid oxidation disorders?

Answer 22

mitochondrial oxidation of fatty acids is one of the major sources of cellular energy, providing up to80% of total energy requirements during fasting. mostly present during prolonged fasting for surgery, or infection, vomiting - hypoketotic hypoglucaemic come. otherwise accumulation of toxic long chain acylcarnitines, particularly in long chain fatty acid oxidation and the carnitine shuttle may affect skeletal muscle and become manifest in adolescence or early adulthood as chornic rela excretion od acylcarnitines can lead to a deficiency.

Question 23

Diagnosis of FFAOD?

Answer 23

1. serum FFAs and ketones
2. hypoglycaemia (ammonis, lactate, CK, myoglobin)
3. carnitine status (serum) free total carnitine
   acylcarnitines
   organic acids
   enzume studies
   molecular studies

Question 24

treatment of FFAOD

Answer 24

avoid fasting
acute: high dose glucose (10mg/kg/min), keep bgl >5.5mmol/l
no IV lipids
LCFAD: dialysis, exhange transfusion.
long term: medium chain triglycerides

Question 25

What is the clinical fx, diagnosis and management of MCAD

Answer 25

The most common FFA disorder 1:6000). Reye like often reapidly progressive metabolic crisis after 8-12-16 hours fasting, during ordinary illness, after surgery etc. Lethargy, nauea, vomiting, often with normal bsl. Diagnosis: high acylcarnitines (c8, c6), urineL c6-10 dicarboxylic acids, hexanolglycine. avoid fasting, normal feeding levels are safe when the child is well. low dose carnitine if free carnitine is low.

Question 26

VLCAD, carnitine transporter deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase, LCHAD,

Answer 26

clinical fx: cardiomyopathy, liver disease, hepatomealy, SIDS. Tx: dietary therapy: medium chain triglycerides, decreased long chain fatty acids, frequent meals, avoid fasting, carnitine sup may be harmful

Question 27

What is Smith-Lemli-Opitz

Answer 27

``` craniofacial dysmorphism (microcephaly, micrognathis, anteverted nostrils, ptosis); syndactly of 2nd and 3rd toes, renal, cardiac, gastrointerstinal and midline malformations including holoprosencephaly, genital malformations. Defect in the last step of cholesterol biosynthesis. Diagnosis: sterols (plasma, fibroblast cultures) Tx: cholesterol (50-100mg/kg), simvastating. Frozen plasma can be given as an emergency source of LDL cholsterol ```

Question 28

GLUTATHIONE SYNTHETASE DEFICIENCY

Answer 28

which is a result of generalized deficiency of the enzyme, severe acidosis and massive 5-oxoprolinuria are the rule 1. Glutathione Synthetase Deficiency 2. GLUTATHIONEMIA (γ-GLUTAMYL TRANSPEPTIDASE DEFICIENCY) 3. Congenital Glutamine Deficiency

Question 29

What are the acute neuropathic porphorias?

Answer 29

acute episodes of severe abdominal pain, limb pain, sympathetic overactivity (tachycardia, hypertension, tremor), vomiting, constipation, electrolyte imblance, mental disturbance, development of peripheral neuropathy, weakness, seizures. pathogenesis: accumulation of highly neurotoxic 5-aminolaevulinic acid + porphobilinogen deaminase (or amnionlaevulate dehydrogenase) triggers: cyp450 inducers, hormones, nutritional factors, smoking, alcohol, stress. diagnosis: high porphonlinogen. Tx: ICU, analgesia, iv glucose, haemin, avoid triggers.

Question 30

what are diseases of lysosomal metabolism?

Answer 30

Genetic defects of lysosomal enzymes usually caude the accumulation of incompletely catabolised substrates within the organelle and progressive impairment of the function of affected cell systems. The cell and consequently the whole organ 'swells' causing organomegaly/

Question 31

how do you diagnose disorders of lysosomal metabolism?

Answer 31

Sx: chronic progression of symptoms without acute metabolic crisi in thh neonatal period: hydrops fetalis, hypotonia, dysmorphia, hypotonis, preogressive orgaomegaly, coarse facial features, skeletal changes ataxia, hyperexcitability, spasticity, cherry red spot. Invx: skeleton, parenchymous organs, eyes, vacuoles in leukocytes, glycosaminoglycans and oligosaccharides in the urine, enzymes in leukocytes and fibroblasts, chitotriosidase in serum.

Question 32

Mucopolysaccharidoses

Answer 32

lysosomal storage disorder disorder of the breakdown of glycosaminoglycans - appear normal at birth, progressive connective tissue (facial dysmorphism, skin changes) skeletsal deformities, growth restritriction, bone dysplasia, contracutres), as well as hepatomegaly and often hernias. progressive psychomotor retardation, with loss of acquired skills , corneal clouding and deafness. Tx: enzyme replacement therapy (MPSI, II, VI) HSCT in presynaptic patients with severe MPS1 and MPS VI

Question 33

MPS I

Answer 33

lysosomal storage disorder Mucopolysaccharidoses: Hurler-Scheie: recurrent URTIs, slowing growth, psychomotor development, progressive hepatosplenomegaly, dysmoprphism, cardiac disease, cornal clouding, death 5-10 years. Enzyme replacement tx

Question 34

MPS2

Answer 34

``` lysosomal storage disorder Mucopolysaccharidoses Hunter x-chromosomal IDS gene - joint contractures and restrictive airway disease, cardiac disease, skeletal deformities, progressive cognitive decline; fstal within 10-20 years. no corneal clouding. Enzyme replacement (iduronate-2-sulphatase) ```

Question 35

MPS3-5

Answer 35

lysosomal storage disorder Mucopolysaccharidoses sanfillippo: encephalopathy with minor organ involvement, seizures, behavioural disturbance Morquio: atlanto-axial instability

Question 36

oligosaccharidoses

Answer 36

are disorders in the breakdown of complex carbohydrate side chains of glycosylated proteins.; resemble MPS but less common. diagnosis: urinary excretion of oligosaccharieds (also in tay sachs, sandoff) Tx: symptomatic, HSCT

Question 37

Sphingolipodoses

Answer 37

major compounds of cellular membranes (ceramide - sphingosine and LCFA) which serves as a hydrophobi ancho on the outside of the cell. clin: progressive psychomotor retardation, neurological problems, specifically epilepsy as well as ataxia and/or spasticity. hepatosplenomegaly is not uncommon, dysmorphism, macula spot, foam cells in the bone marrow or vaculated lymphocytes. Neurological and neuroradiological findings are not always specific.

Question 38

GM1:

Answer 38

GM1: gangliocidosis Acid B-galactosidase removes galactose from GM1 gangliosides - GLB1 and GM1 gene. TI: neonatal hypotonia, sometimes edema, facial dysmorphism, arrest of neurological development - decerebration, death before age 2. Type II: late infantile/juvenile presentation with ataxia, no dysmorphism, mild bone changes, no hepatosplenomegaly. Dx: vacuolared lymphocytes; oligosaccharides/ GAG

Question 39

GM2

Answer 39

GM2: gangliocidosis: Tay sachs and sandhoff - infantile: 4-6 months, hypotonia, cherry red spot, blindness, spastic tetrapareesis, decerebration, macrocephaly. Late infantile: ataxia, incoordination, dysarthria, myoclonus. vacuolated lymphocutes or elevated urinary oligosaccharides.

Question 40

Metachromatic leukodystrophy

Answer 40

lysosomal storage disorder gene: ARSA central and peripheral demyelination (tiger stripes on MRI), spasticity, neuropathy, loss of skills, fatal age 3-6. dx: increased CSF protein, HSCT

Question 41

Krabbe

Answer 41

``` lysosomal storage disorder Globoid cell leukodystrophy Galactosylceramidase. GALC gene central and peripheral demyelination, startle reaction, fever, spasticiy - fatal before age 2. increased csf protein decreased nerve conduction. tx: HSCT may be effective ```

Question 42

Gaucher

Answer 42

lysosomal storage disorder Non neuronopathic form, manifestation in infancy to adulthood with visceral, haematological and skeletal symptoms. - hepatosplenomegaly, anaemia, thrombocytopenia,bleeding tendency, acute abdomen (splenic infarctions, acute bone crises, osteonecrosis, osteopenia, fractures, growth rsstriction, lung fibrosis, normal intelligence, no CNS involvement II - Acute neuronopathic form - rapidly progressing in infancy, brainstem dysfunction (opthalmoplegia, dysphagia, spasticity, hepatosplenomegaly. fatal within 2 years. III chronich neuronopathic form (between I and II) dx: increased acid phosphatase, 'gaucher cells in bone marrow, chitotriosidase (in serum) enzyme replacement therapy

Question 43

Niemann-Pick

Answer 43

lysosomal storage disorder Type A) Sphingomyelinase deficiency; feeding problems, hypotonia, FTT, lymphadenopathy, neurological deterioration, fatal within 1.5-3 years Type b - normal intelligence and lifespan 'niemann-pick cells' in bone marrow Type C: disorder of cellular cholesterol trafficking - cholesterol storage with secondary storage of sphingomuelin and glycosphingolipids. NPC1 NPC2 (juvenile - 2-5, progresive ataxia, language delay, behaviour problems, hepatosplenomegaly). Niemann-Pick cells in fibroblasts. Substrate inhibition therapy.

Question 44

Fabry disease

Answer 44

lysosomal storage disorder X linked (GLA gene) manifestation in the first decade, recurrent pain and parasthesia in limbs lasting hours to days. Enzyme replacement

Question 45

Farber disease

Answer 45

lysosomal storage disorder ceramidase (ASAH gene) Painful contractrues/joint deformities, hoarseness, skin nodules, neurodegeneration. HSCT

Question 46

ceroid lipofuscinoses

Answer 46

Neuronal ceroid lipofuscinoses - most common neurometabolic disorder - seizures -progressive deterioration of cognition - motor dysfunction - progressive loss of vision (retinopathy, optic atrophy, nystagmys) deceleration of head growth, microcephaly dx: microscopy (skin biopsy, lymphocytes), distinct storage patterns, vacuolated lymphocytes.

Question 47

peroxisomal biogenesis

Answer 47

PEX mutations 1. Zellweger syndrome: severe hypotonia, seizures, liver dysfunction, jaundice, hepatomegaly, portal hypertension, FTT, dysmorphic, skeletal abnormalities, sensorineural deadness, retinopathy, progressive white matter disease, fatal within a few months. disorders of B oxidation are very similar to biogenesis.

Question 48

What is the biochemistry of peroxisomal metabolism

Answer 48

b-oxidation of VLCFA, pristanic acid and intermediates of bile acid synthesis: detoxification and oxygen dependent reactions which occurs inside the peroxisomes to protect the cell against free oxygen radicals. various peroxins encoded by PEX genes are required for peroxisome biogenesis.

Question 49

what are the clinical features of disorders of peroxisomal metabolism?

Answer 49

1. neurological abnormalities - hypotonia, encephalopathy, seizures, deafness, retinopathy, cataract, blindness 2. skeletal abnormalities - short limbs, calcific stippline 3. Dysmorphic features - high forehead, large fontanels, shallow supraorbital ridges, epicanthic folds, micrognathis, minor ear anomalies 3. Hepatointestinal dysfunction - neonatal hepatitis, hepatomegaly, cholestasis, cirrhosis etc.

Question 50

major diagnostic features of disorders of peroxisomal metabolism?

Answer 50

1. decreased cholesterol, increased bilirubin, abnormal LFTs 2. VLCFA in cerum and increased C26 indicates deficient peroxisomal B oxidation 3. Plasmalogens (erythrocytes): reduced in disorders affecting etherlipid biosynthesis 4. phytanic acids (deficient a oxidation) pristanic acids (reduced in a-oxidation) bile acid intermediates (serum, urine) enzyme studies, murtation analyses.

Question 51

Rhizomelic chondrodysplacia punctata

Answer 51

Small stature, proximal shortening, facial dysmorphism microcephaly, congenital cataracts, contractures, spacticity, mental disabilith. Due to deficient ethetphospholipid biosynthesis. See mostly increased phtytanic acid, and decreased pristanic acid.

Question 52

X-lined adrenoleukodystrophy

Answer 52

x linked; Most common peroxisomal disorder (1:20000). a) Childhood cerebral form - boys 4-12; school failur, visual/hearing imparirment, intellectual regression, ataxia, adrenal insufficiency, leukodystrophy - decerebration within 2-4 years. Adrenomyeloneuropathy: AMN, males early adults 20% of females >35 years) genetics ABCD gene (Xq28), de novo mutations in 7% of affected boys. diagnosis increased hexacosanoic acid (C26:0, VLCFA plasma) Tx: early HSC transplantation, gene therapy; Lorenzo's oil (glyceril trioleate + glyceryl Trierucate) may reduce risk for childhood cerebral form.

Question 53

Refsum disease

Answer 53

clinical: retinitis pigmentosa, polyneuropathy, cerebellar ataxia, deafness, anosmia, icthyosis, skeletal and cardiac symptoms normal intelligence; alpha oxidation defects; phytanic acid restricted diet, plasma pheresis

Question 54

Acatalasaemia, Primary hyperoxaluria Type 1, Mulibrey nanism

Answer 54

other peroxisomal enxyme deficiencies

Question 55

Disorders of copper metabolism?

Answer 55

1. Wilson disease | 2. Menke kinky hair

Question 56

Features of Wilson disease?

Answer 56

(hepatolenticular degeneration): chronic liver disease, cirrosis, kayser-Fleisher ring, dysarthria, poor coordination, bulbar paralysis, renal problems, haemolysis. 6-8 yrs, disorder of hepatic copper binding P-type ATPase. biochem: serum decreased ceruloplasmin, decreased copper in serum, increased urinary coppe,

Question 57

Features of Menke kinky hair syndrome?

Answer 57

classical - kinky hair, tissues/bone abnormalities, ataxia, dysarthria. occipital horn syndrome - laxity of skin and soft tissues; exostosis (occipital horn) copper deficiency as defective intestinal uptake of Cu. Serum decreased copper and ceruloplasm (protein that carries copper). Tx: early copper-histadine subcutaneous injections (50-150ug/day)

Question 58

example of Disorders of amino acid transport

Answer 58

1. Lysinuric protein intolerance: FTT/diarrhoea, interstitial pneumonia, osteoporosis, renal failure, haemolysis, hyperammonaemia (dx: increased ammonia, LDH, Ferretin), Arginine, lysine, ornithine increased in urine and decreased in plasma. tx: citrulline substitution. 2. Cystinuria: nepholithiasis; tx is high fluid intake and alkialinsation of the urine. 3. Hartnup disease: photodermatitis, cerebellar ataxia; can't reabsorb neutral amino acids. SLC6A19 gene. Ddx: fanconi syndrome; Tx: nicotinamide/sun protection 4. Iminoglycinuria: asymptomatic

Question 59

what are the ceroid lipofuscinoses?

Answer 59

1. Neonatal 2. congenital: microcephaly and seizures infantile (sanravuori-Haltia disease) 3. Later infantile (Jansky-Bielschowski disease) 4. Juvenile form (batten disease, vogt-spielmeyer disease) 4-10 years, often rapid loss of vision - blindness, epilepsy, regression, behavioural distrubances, hallucinations, disturbed sleep patterns, parkinsonian like disease, die early adulthood

Question 60

what are the groups within this lysosomal metabolism?

Answer 60

1. mucopolysaccharisoses (deficient breakdown of glycosaminoglycans) 2. oligosaccharidoses (deficient breakdown of carbohydrate side chains from glycoproteins 3. sphingolipidoses: deficient breakdown of ceramide- containing membrane lipis 4. neuronal ceroid lipofuscinoses 5. lysosomal export defects lysosomes are required for the intracellular breakdown of various molecules and compounds of all sized. They are therefore secreted and taken up by other cells through endocytosis and can be measured in body fluids

Question 61

What are the branched chain amino acids?

Answer 61

Leucine, Isoleucine and valine

Question 62

What is the characteristic disorder of Branch-chain keto-acid dehydrogenase deficiency catabolism?

Answer 62

MSUD - the accumulation of the leucine, isoleucine and valine cause the maple syrup smell

Question 63

What is the Ddx for chronic encephalopathy assoc with the following extra CNS abnormalities? a) muscle b) hepatospleno megaly/bone c) skin/connective tissue

Answer 63

a) mitochondrial b) Lysosomal storage, Peroxisoma, c) Homocysteinuria, menkes

Question 64

which are the only two lyusosomal storage disorders that are not AR in genetic inheritance?

Answer 64

Fabry and hunter (MPS2) are x linked

Question 65

What are the most common lysosomal storage disorders?

Answer 65

1. Gaucher, 2. MPS1, 3. Metachromatic leukodystrophy, 4. MPSIIIa, 5. Fabry, 6. MPSII, 7. Krabbe, 8. Pompe, 9. MPS IVA, 10. Cystinosis, 11. TaySachs, 12. MPS IIIB, 13. Neiman-pickC

Question 66

What are the major features of lysosomal storage disorders?

Answer 66

Phenotype: macrocephaly, coarse facial fx, macroglossia, corneal clouding, hepatosplenomegaly, inguinal, umbi hernias ENT: chronic rhinnorhea, recurrent OM, enlarged tonsils, OSA, hearing loss Cardiac: cardiomyopathy, valvular disease Respiratory: recurrent lower resp infections, reactive airways disease Neurodevelopmentals: developmental delay, cognitive impairment, behavioural problems, seizures Musculoskeletal: dystostosis multiplex, lumbar kyphosis

Question 67

major manifestation of MPSII radiologically

Answer 67

Metacarpals: proximal pointing Metacapraps: thick, short with thin cortices Carpal bones: irregular, hypoplastic rounded vertebral bodies, anteror beaking, posteriorly thin ribs that widen anteriorly proximal humerus thin

Question 68

which MPS respond to Enzyme replacement therapy?

Answer 68

MPS I, II, IVA, VI. | MPS I, II, VI also HSCT

Question 69

What is Pompe disease?

Answer 69

Glycogen storage disorder type II deficiency of acid alpha-glucosidase (GAA) progressive accumulation of lysosomal glycogen - particularly in cardiac, skeletal and smooth muscle. sx: cardiomyopathy, cardiomegaly, macroglossia, FTT, resp insufficiency, CCF rapidly fatal

Question 70

What is the most recognisable feature of Lesch-Nyhan disease?

Answer 70

self mutilation of mouth Very rare x-linked disorder of purine salvage (hypoxanthine phosphoribosyltransferase) 1:400 000 hyperuricaemia

Question 71

DDx for severe hypotonia

Answer 71

Pompe disease peroxisomal disorders mitochondiral respiratory chain disorders

Question 72

clinical features of mitochondial disorders?

Answer 72

``` neonatal lactic acidaemia unexplained multiorgan failure skeletal myopathy, exercise intolerance cardiomyopathy hepatopathy, intestinal pseucoobstruction encephalopathy sideroplastice anaemia renal tubulopathy cateract, retinitisc, optic hypoplasia, opthalmoplesia, sensorinerual deafness panreatic insufficiency ```

Question 73

what are the key fx of MELAS?

Answer 73

Michochondrial Encephalopathy, Lactic acidosis and stroke like episodes - recurrent stroke like episodes (confusion, blindness, vomiting, transient blindness, seizures), often recover completely, progressive neuromusc abnormalities

Question 74

best approximation for basal energy requirement for ages?

Answer 74

6mg/min for fasting child 2mg/kg/min in a fasting adult this flux decreases as the fasting proglongs 8.3mg/kg/min of 10% glucose @5ml/kg/hour