Metabolism Flashcards

1
Q

Metabolism definition

A

sum of all chemical reactions occurring within the cells of the body

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2
Q

Goal of metabolism

A

Maintain a constant source of energy for the body

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3
Q

Polysaccharides

A

Complex carbs

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4
Q

Monosaccharides

A

Simple sugars (mostly glucose)

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5
Q

What is the primary energy source of the body

A

Glucose

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6
Q

What is excess glucose stored as

A

glycogen

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7
Q

Where is glycogen stored

A

Liver and muscle

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8
Q

What is glucose converted into once glycogen stores are full

A

fatty acids and glycerol

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9
Q

What does glycerol get converted to in storage

A

Triglycerides

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10
Q

How many essential amino acids are there

A

9

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11
Q

How many non-essential amino acids are there

A

11

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12
Q

What are essential amino acids

A

Amino acids that aren’t created by the body

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13
Q

Extra amino acids are converted to

A

Glucose and fatty acids (fatty acids eventually stored as triglycerides)

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14
Q

Three types of fats

A

Triglycerides, monoglycerides, and free fatty acids

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15
Q

Excess circulating fatty acids are incorporated into

A

triglycerides

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16
Q

Where are triglycerides stored

A

mostly adipose tissue (fat), some muscle

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17
Q

Stages of energy use in the body

A

Glycogenolysis, gluconeogenesis, ketogenesis

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18
Q

Glycogenolysis time

A

1 hour after eating

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19
Q

Gluconeogenesis time

A

5 hours after eating

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20
Q

Ketogenesis time

A

10-12 hours after eating

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21
Q

Glycogenolysis definition

A

breakdown of glycogen into glucose (1-4 hours of fasting)

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22
Q

Gluconeogenesis definition

A

New creation of glucose from amino acids (3-12 hours of fasting)

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23
Q

Ketogenesis definition

A

fatty acid oxidation, creation of ketones from fatty acids (10+ hours of fasting)

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24
Q

Anabolism

A

Feeding/fed state
Buildup (synthesis) of larger organic macromolecules from smaller subunits

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25
Anabolism results
Manufacture of material needed in the cell Storage of excess ingested nutrients that are not immediately needed for energy production or as cellular building blocks
26
Catabolism
Fasting state Breakdown (degradation) of large, energy-rich organic molecules within cells
27
Catabolism results
Breakdown of stored energy resources into smaller nutrients available for energy use (glycogen to glucose)
28
Primary energy users of the body
brain and muscle
29
Preferred source of energy for the brain
Glucose (can't store glycogen) Prolonged fasting can lead to brain using ketones
30
Primary site for amino acid storage
Muscle
31
Which organ is concerned with maintenance of normal blood glucose levels
Liver Stores glycogen when excess glucose is available Releases glucose into blood when needed Principal site for conversion of glycogen into glucose
32
Other functions of liver
Production of enzymes for blood clotting Metabolism of bilirubin
33
Primary energy storage site
Adipose tissue
34
Adipose tissue helps regulate what
fatty acid levels in blood
35
Lysosomes do what
Intracellular digestion
36
What happens if lysosomal enzyme doesn't work
massive buildup/storage of material can cause lysosome to swell and burst
37
Mitochondria do what
Energy organelles that are powerhouse of cell
38
How do mitochondria work
Extract energy from nutrients via mitochondrial oxidation phosphorylation (respiratory chain) B-oxidation of fatty acids
39
Peroxisomes do what
Intracellular waste treatment center
40
Major product of peroxisome
Hydrogen peroxide (H2O2)
41
Peroxisomes contain what
enzymes responsible for processing B oxidation of very long chain fatty acids (VLCFA)
42
Emia suffix
Regarding the blood
43
Uria suffix
Regarding the urine
44
Hyper prefix
too much
45
Hypo prefix
too little
46
Lys suffix
break down
47
Genesis suffix
creation
48
cofactor
Helper molecules for enzymes Vitamins and minerals
49
Inborn errors of metabolism (IEMs) disease mechanism
Toxic accumulation of substances Reduction of normal compounds
50
IEMs are usually caused by what
single-gene disorders Code for enzymes that convert substrate into product
51
How many IEMs are there
1000
52
Incidence of IEMs
1/1500
53
Most IEMs have what inheritance pattern
AR Can be X-linked or AD
54
Continuum of disease
Acute (PKU) Late-onset (Gaucher)
55
Acute IEMs
Onset early in life Severe if untreated Progressive
56
Late onset IEMs
Onset may be in adulthood Can live long time without treatment Progressive
57
Genetic mutations of IEMs cause
reduced activity of enzyme Reduce or lessen effectiveness of cofactors or activators for the enzyme Produce defective transportation of compounds in the bodyl
58
Disruptions of metabolic pathway can cause
shunting of accumulated substrates on other pathways Accumulation of toxic substrates/products Deficient products of the missing enzyme
59
Treatment of IEMs
Limit substrate and substrate precursors Process toxic products through alternative pathways Supplement cofactor Provide missing enzyme (enzyme replacement therarpy/transplant) Supplement products and downstream products
60
Clinical features of IEMs in infant/child
Vomiting, seizures, ataxia, lethargy, coma, hepato-encephalopathy Dysmorphic (coarse) features Skeletal abnormalities Poor feeding, FTT Dilated or hypertrophic cardiomyopathy, hepatomegaly, jaundice, and liver dysfunction Developmental delays Hypotonia/hypertonia Visual/auditory disturbances
61
Clinical features of IEMs in older children/adults
Varying degrees of LD/DD/ID, autism Exercise intolerance Muscle weakness (can be progressive) Behavioral disturbances (delirium, hallucinations, agitation, aggressiveness) Ataxia Anxiety/panic attacks Seizures
62
Episodes of symptoms for IEMs can be
Acute Intermittent Precipitated by stress (mental and physical-infection, pregnancy) Progressive Associated with feeding
63
Hypoglycemia
Normal: 70-140 mg/dl (80-120) Hypoglycemia in children: <50 mg/dl Hypoglycemia in adults: <55 mg/dl
64
Glucose is recovered from three different sources
Exogenous glucose via food is used immediately, excess stored in liver as glycogen Liver glycogen maintains fasting blood glucose via continuous glycogenolysis - capacity for storage in this form is relatively small and can provide gluocse for 24-48 hours Gluconeogenesis: formation of glucose from amino acids and other sugars - occurs coincidentally with glycogenolysis but can supply glucose for much longer period of time
65
Energy production alternatives for hypoglycemia
Fatty acid oxidation Ketone production and oxidation (brain) Metabolism of lactate
66
IEMs with hypoglycemia as prominent component
Glycogen storage disease type 1 - carb metabolism MCAD deficiency - fat metabolism
67
IEMs with hypoglycemia as secondary component
Disorders of protein metabolism Mitochondrial disease
68
Hyperammonemia
Normal <80 umol/l Elevated >80 umol/l
69
Ammonia
NH4 Constantly produced by liver, intestinal mucosa, and kidneys
70
How is free ammonia removed from the blood
By the liver and kidneys Excreted in urine as urea after traveling through the urea cycle
71
What happens when ammonia accumulates
Disrupts ATP production
72
Neurologic symptoms frequently result from
hyperammonemia
73
Many disorders with hyperammonemia present
after initial asymptomatic/normal period following birth Stress - labor and delivery, inter-current infections
74
Significant hyperammonemia
>300 umol/l - 1000 umol/l
75
Urea cycle defects have what level of hyperammonemia
10-100X above normal
76
2-3x above normal level of hyperammonemia can be seen in
mitochondrial disorders and other protein metabolism problems
77
pH
normal 7.4 Acidosis - <7.35 Alkalosis - >7.45
78
How is pH caluclated
logarithmic of hydrogen-ion concentration Every unit change in pH is tenfold change in H+
79
Excretion of H+ makes
CO2
80
Respiratory alkalosis
caused by excessive loss of CO2 as a result of hyperventilation
81
Respiratory acidosis
Caused by abnormal CO2 retention arising from hypoventilation
82
Metabolic alkalosis
Reduction of plasma (H+) arises most commonly from - vomiting, ingestion of alkaline drugs such as calcium carbonate
83
Metabolic acidosis
Caused by net gain of H+ or loss of HCO3- (bicarbonate) Encompasses all types of acidosis besides that caused by excessive CO2 in body fluids
84
Metabolic acidosis arises from
severe diarrhea, diabetes mellitus, strenuous exercise, and severe renal failur
85
Metabolic acidosis secondary causes
severe infection/sepsis, advanced catabolic state, tissue hypoxia, dehydration, and intoxication
86
Anion gap
difference between major cations (NA+ and K+) and major measured anions (Cl- and bicarbonate)
87
Normal anion gap
<16
88
Possible reasons for anion gap increase
lactate, ketones, organic acids Can be measured in blood or urine
89
Primary IEMs associated with metabolic acidosis
Disorders of protein metabolism Disorders of fat metabolism Mitochondrial disease
90
Lactic acidosis
Too much lactic acid in blood
91
Best diagnostic markers for disturbed mitochondrial energy metabolism
Elevated lactate and pyruvate
92
Lactate is produced from
Pyruvate
93
Lactate is easier to measure than pyruvate by
blood and spinal fluid
94
Plasma lactate levels increase by what two mechanisms
Increased pyruvate production (glycolysis) Decreased pyruvate consumption/oxidation (by pyruvate dehydrogenase complex or pyruvate carboxylase)
95
Primary hyperlacticacidemia
Carbohydrate metabolism (disorders of liver glycogen metabolism) Mitochondrial disease (electron transport/respiratory chain defects)
96
Secondary hyperlacticacidemia
Protein or fat metabolism (organic acidemias, urea cycle defects, fatty acid oxidation defects)
97
Ketoacidosis
Acidosis caused by too many ketones
98
How are ketones formed
excess acetyl-CoA (involved in carbohydrate and lipid metabolism) Used as alternative energy sources in tissues
99
Ketones are formed by
liver during times of fasting
100
Ketoacidosis from
Ketone utilization or increased ketone production
101
Ketoacidosis is usually what type of result of metabolic disorders
secondary
102
Creatine Kinase (CK)
Provides information regarding muscle breakdown and injury
103
Creatine kinase levels
Normal for adult 22-170 U/L
104
Serum CK levels can be due to
Muscle damage Elevations due to acute muscle trauma elevated 4-6 hours after event Peak values 18-30 hours Return to normal by 72 hours
105
CK-MB isoenzyme
Measure of cardiac muscle damage
106
Rhabdomyolysis
Sudden increase in serum concentrations of CK
107
Rhabdomyolysis can be observed in
Carbs, fat, and mitochondrial IEMs associated with muscle disease
108
Myoglobinuria
Muscle tissue pigment in urine Severe rhabdomyolysis
109
Carnitine
Fatty acids and proteins are broken down and their backbone structures are attached to carnitine Shuttle across mitochondrial membrane and within mitochondria as they are metabolized into energy/ATP (move carbon chain backbones) Help with transport of LCFAs
110
Carbon chain backbones are broken down by mitochondria by
B-oxidation Used t provide energy in form of ATP
111
Two forms of carnitine
bound and free - describes carrier state
112
Bound carnitine-carbon complexes
varying lengths and are acylcarnitines Divided into lengths - very long, long, medium, and short
113
Defects in carbohydrate metabolism
Galactosemia Hereditary Fructose Intolerance Glycogen storage disease (GSD)
114
Hepatic forms of glycogen storage
GSD1 - von Gierke's disease GSD III - Cori Disease Enlarged liver - excess glycogen Treatment with cornstarch
115
Muscular forms of GSD
GSD II - Pompe disease (also a lysosomal storage disease) GSD V - McArdle's disease
116
Galactosemia
Due to deficient activity of galactose - I - phosphate uridyltransferase (GALT) GALT catalyzes production of UPD galactose from galactose-I-Phosphate and UDP glucose Gene at 9p13 AR
117
Classic galactosemia
complete or near complete enzyme deficiency - 5% or less
118
Partial transferase deficiency galactosemia
More frequent than classic galactosemia Enzyme activity 10-50% of normal Generally asymptomatic Duarte variant is best known
119
Newborn screening diagnosis of Galactosemia
high levels of Galactose-I-Phosphate Confirm diagnosis by enzyme deficiency (GALT) in heparinized whole blood or RBC In classic form GALT is almost complete (0%)
120
Mutation panel and sequence analysis of GALT
For classic (G/G) - panel of 6 common mutations 71%: two common mutations 10%: one common mutation and one private mutation 19%: two private mutations
121
Clinical features of Galactosemia
Feeding problems/vomiting/diarrhea Lethargy FTT Hypoglycemia Liver failure/jaundice Bleeding Sepsis/shock Females - increased risk for primary or secondary premature ovarian failure (75-96% before age 30) DD/ID Cataracts Delayed growth Speech apraxia
122
Treatment for Galactosemia
Immediate dietary intervention for infants with GALT activity less than 10% Begin formula that is lactose free Calcium supplementation
123
Defects in protein metabolism
PKU (maternal PKU, defects in biopterin) Tyrosinemia Alcaptonuria Homocystinuria Nonketotic hyperglycinemia
124
PAH Deficiency
Phenylalanine hydroxylase
125
Severe PAH deficiency
Classic PKU Classic, moderate, and mild forms tolerate different levels of Phe in diet
126
Maternal PKU
Poor control of plasma Phe levels during pregnancy adversely affects fetal development Growth restriction Microcephaly Birth defects
127
Diagnosis of PKU
Newborn screening
128
Untreated PKU infants will
develop typically for first few months and then start showing symptoms Seizures Severe-profound ID Microcephaly Behavioral problems Mousy odor (urine) Very light skin and hair
129
PKU geneitcs
PAH AR
130
Treatment of PKU
Diet some Phe needed for normal growth/development Avoidance of high-Phe foods (meat, fish, eggs-high protein foods) Use of Phe-free formula as supplement (Tyrosine) Phe restriction life long Keep blood Phe 120-360 umol/L
131
Biopterin Cofactor Deficiency Tetrahydrobiopterin (BH4)
2% of hyperphenylalaninemias
132
Biopterin recycling defects
Dihydropteridine reductase (DHPR) deficiency Pterin-4 acarbinolamine dehydratase (PCD) deficiency
133
Biopterin synthesis defects
Guanosine triphosphate cyclohydrolase (GTPCH) deficiency 6-pyruvoyl tetrahydrobiopterin synthase (PTPS) deficiency
134
Diagnosis for BH4
CHPR and biopterin in blood spot Urine biopterins
135
High neopterin, low biopterin
biopterin recycling defect
136
low neopterin, low biopterin
pterin synthesis defect
137
Urea cycle defects
Urea cycle rids body of waste nitrogen
138
Waste nitrogen mostly from
amino acid metabolism
139
Product of protein catabolism
Ammonia
140
What organ conjugates waste nitrogen as ureea
Liver Excreted by kidneys
141
Inherited defect of urea cycle manifests as
elevated blood ammonia - toxic to brain
142
Urea Cycle defects inside
Ornithine transcarbamylase (OTC) deficiency - one of few that is X-linked Argininosuccinate synthetase deficiency - citrullinemia Arginosuccinic aciduria - ASA lyase deficiency Argininemia - Arginase deficiency
143
Urea cycle defects outside
NAGS - secondary inhibition by organic acids CPS - Carbamyl phosphate synthetase deficiency
144
Urea Cycle defects treatment
Precursor and substrate restriction - dietary protein restriction Provide/supplement deficient enzyme - liver transplant Increase alternative pathway use - oral medications to help remove nitrogen via alternative mechanisms Supplement products - citrulline or arginine supplementation
145
Organic acidurias
Maple syrup urine disease (MSUD) Isovaleric aciduria (IVA) 3-methyl crotonyl-CoA carboxylase (3MCC) deficiency Methylmalonic acidemia (MMA) Propionic aciduria (PA) Glutaric acidemia, Type I (GA I) Biotinidase deficiency
146
Classical Organic acidurias features
Usually well at birth and for first few days Toxic encephalopathy Vomiting Poor feeding Hypotonia Lethargy progressing to coma Macrocephaly Seizures Metabolic acidosis - organic acids accumulate Secondary hyperammonemia
147
Cerebral organic acidurias features
Cerebral (neurological) symptoms without the typical metabolic/lactic acidosis and hypoglycemia
148
Treatment of organic acidurias
Diet control - AA supplementation, AA avoidance, Carnitine supplementation Emergency protocol - Carnitine supplementation increase during times of stress, avoidance of fasting (catabolic state) Treatment is lifelong
149
Unusual odors in urine
Maple syrup - MSUD Cat urine (ammonia) - 3MCC deficiency Sweaty feet - IVA Mousy - PKU
150
Fatty acids are released by
Lipoprotein lipase and hepatic lipase cleaving triglycerides, in endothelial cell and on surface of hepatocytes
151
Triglycerides released from
fat cells
152
Triglycerides convert to
glycerol and 3 fatty acids
153
FAOD
Fatty acid oxidation disorder
154
Mitochondria store energy in forms of
ATP from ADP and phosphate
155
Defects of fat metabolism
VLCAD deficiency LCHAD deficiency Trifunctional protein (TFP) deficiency MCAD deficiency SCAD deficiency Short chain L-3-Hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency - now 3-hydroxy acyl CoA dehydrogenase deficiency (HADH) Electron transfer flavoprotein (ETF) dehydrogenase deficiency 3-Hydroxy-3 Methylglutaryl-CoA Lyase Deficiency (HMG)
156
Carnitine disorders
Carnitine transport defect - main one Carnitine-acylcarnitine translocase deficiency Carnitine Palmitoyl Transferase I and II
157
Clinical features of FAO defects
cause infant or childhood deaths, following minor illness with fasting Affect multiple siblings in a family Associated symptoms: hypoglycemia, coma, seizures, heart failure, muscle breakdown
158
Treatment of FAO defects
dietary management
159
MCAD deficiency
Gene ACADM Common mutation - 985A>G, K304E - 90% 80% homozygous 1:40 carriers among Northern Europeans Low plasma carnitine, high medium-chain acylcarnitines
160
Symptoms of MCAD deficiency
Vomiting, lethargy, seizures, breathing difficulties, brain damage, coma, sudden death (from hypoketotic hypoglycemia when ill/fasting
161
MCAD Treatment
Typical infant feeding 30% calories from fat Supplement carnitine as needed Avoidance of prolonged fasts Understand chronic health needs
162
Peroxisomal disorders
X-linked adrenoleukodystrophy (X-ALD) - Lorenzo's Oil
163
Porphyrias disorders
Defects in synthesis of heme Can be acute (neurologic) or cutaneous (primarily affect skin) Photosensitivity, mental disturbances, hepatic disease
164
Purines and Pyrimidines disorders
Lesch-Nyhan Syndrome - X-link recessive, self-injurious behavior
165
Metal metabolism disorders
Hemochromatosis - iron metabolism Wilson disease - copper metabolism Menkes disease - copper metabolism - X-linked characterized by sparse, kinky hair, FTT, and neurological sx
166
Bone metabolism/mineralization disorders
Familial X-linked hypophosphatemic Rickets (XL dominant) Hypophosphatasia (AR or AD)
167
Cholesterol metabolism disorders
Smith-Lemli-Opitz Syndrome (SLOS)
168
Congenital disorders of glycosylation (CDG) syndromes
Variable, umbrella term for disorders involving glycoproteins/glycolipids
169
Goals of medical nutrition therapy
Promote healthy brain function - prevention of neurlogical damage d/t metabolic crises/decompensation, preserve cognition/intellect Promote healthy physical growth and development - prevention of malnutrition or FTT, growth delay, poor bone health, support healthy weight and exercise
170
Challenges of medical nutrition therapy (MNT)
Introduction of foods as patients age Adherence to diet Family member/caregiver compliance Adolescence Emergency situations
171
Macronutrients
Carbs (glucose) - fuel brain/body, fiber Protein (essential amino acids) - required for growth, cell repair, enzyme formation Fats (EFS0: protection, temperature regulation, hormone regulation, energy
172
Micronutrients
Vitamins (fat and water soluble) - hormones, enzymes, co-enzymes Minerals (major and trace) - bone and tissue health
173
Simple sugars
table sugar, jelly, candy, honey, syrup, fruit, fruit juice - quick sources of energy
174
Complex carbs
Cereals, breads, grains, pasta, potatos, beans, corn, veggies - helps with prolonged glucose release
175
Goals for carb disorders
avoid prolonged periods of fasting Restrict the offending simple sugar Provide adequate nutrients to promote normal growth and development Prevent hypoglycemia which can progress to metabolic crisis, seizures, and death Laboratory monitoring: lactic acid, uric acid, blood glucose
176
GSD Type IA
Enzyme defect - Glucose-6-phosphate Roadblock is final step of gluconeogenesis - glycogenolysis to release glucose - no internal source of glucose Can store glycogen but can't break it down Uncontrolled leads to hypoglycemia, lactic acidosis, high uric acid, elevated TGs, cholesterol Can progress to seizures and death
177
Nutrition guidelines for GSD IA
High protein, low carb diet - restrict fructose (sucrose), limit lactose (galactose), sucrose and lactose free formula, consume complex carbs Nighttime feedings Limit fat, especially saturated fat Possible G-tube Dairy to one serving per day Limit fats and choose mono-unsaturated fats Multivitamin+calcium citrate supplementation Avoid sucrose and fructose Avoid sorbitol
178
Tyrosinemia IA
Enzyme defect: hepatic fumarylacetoacetate hydrolase (FAH) Buildup of succinylacetone which is toxic to the liver needs dietary management and medication
179
Essential FAs
Linoleic acid Alpha-linolenic acid
180
Medical food
food which is formulated to be consumed or administered entirely under supervision of physician and intended for specific dietary management of disease
181
Dietary supplement
product taken by mouth that contains a dietary ingredient
182
PKU
Body cannot metabolize essential AA, phenylalanine
183
Criteria for NBS conditions
Wilson and Jungner criteria condition should be important health problem Natural history of condition should be well understood Recognizable latent or early symptomatic stage Suitable tst or examination Test should be acceptable to population Should be agreed upon policy on who to treat Accepted treatment for patients with disease Must have facilities for diagnosis and treatment Cost of case-finding should be economically balanced in relation to possible expenditure on medical care as whole Case finding should be continuing process
184
Tandem mass spec
multiplex analysis of many different analytes
185
NBS tests
heel prick Cardiac screen Hearing screen
186
When is blood spot collected for NBS
24-48 hours after birth
187
Steps after positive NBS
Diagnostic confirmation Intervention Medical management
188
Sudden increase in CK, evidence of muscle breakdown, and urine that looks like cola
Rhabdomyolysis
189
Cataracts, jaundice, vomiting, lethargy
Classic Galactosemia