Peadiatric Biochemisty INBORN ERRORS OF METABOLISM

• IOC / Gold standard: Tandem Mass Spectrometry:
• Blood spot

• Gas Chromatography - Mass Spectrometry:
• Fresh Urine

• High Performance Liquid chromatography/Electrophoresis:
• Plasma, urine

Intolerences and ages

• Immediately in neonates
• Galactosemia
• Lactose intolerence

• While Weaning
• Fuctose intolerence

• In young children
• Celiac disease

• Mnemonic: Galact (GALT) Galact (Galactokinase) Appi (Epimerase)

Meconium ileus

Causes

1. Prematurity

2. Hypothyroidism

3. Cystic Fibrosis
• Present with other features of CF
• Soap bubble appearance
• NO AIR FLUID LEVEL (dry thick impacted meconium)
• Bishop Koop surgery
• Stippled calcification d/t inspissated stools

4. Hirschsprung disease
• present within 48hrs,
• abdominal distension and bilious vomiting
• On per rectal examination
• On removal of finger
• Sudden expulsion of meconium d/t transient dilatation

5. Anorectal malformation

6. Lazy Left colon syndrome
• Infant of Diabetic mother
• d/t ↓ gut motility → delayed passing of meconium

 

• Cause:
• Deficiency of phenylalanine hydroxylase

• Tyrosine becomes essential

• Clinical:
• Hypopigmentation (fair skin (Blond), blue eyes)
• D/t ↓↓ Tyrosine

• Intellectual disability
• by competing at BBB with other Neutral amino acids
• Seizures
• Mousy odor
• ↑↑ Phenyl acetate
• Ass smells
• Persistence of neurological symptoms
• after phenylalanine restriction → Non-classic PKU

• Lab
• IOC: TMS
• Positive Ferric chloride test
• d/t Phenylpyruvate
• Payaril () Iron (FeCl3) und
• put Iron (FeCl3) in Fire (Pyruvate)



• Guthrie’s test (Bacterial inhibition test) :
• Growth of Bacillus subtilis.
• Blood phenyl alanine levels
• Enzyme studies.

• Treatment:
• Phenylalanine restricted diet
• Synthetic tetrahydrobiopterin (THB)
• in Non-classic PKU
• Drug: Sapropterin dihydrochloride (Kuvan)
• Large neutral amino acids supplementation
• Tryptophan
• Tyrosine

• A disorder characterized by:
• Fair complexion
• Accelerated atherosclerosis and thrombosis.
• Skeletal deformities
• flat foot
• Charlie Chaplin gait
• Marfanoid habitus
• Chest wall deformities
• Subluxation of eyes
• Inferomedial ectopia lentis
• Stroke episodes
• Hypercoagulable state

• Differentiate from Marfans by
• Fair complexion
• Inferomedial ectopia lentis

• Treatment:
• Pyridoxine, folic acid
• Restrict methionine
• Supplement cysteine

• Mnemonic: Pyramid (Pyridoxine supplementaion) nte mukalil keri thazhott (Inferomedial ectopia lentis) nokkum

• Mnemonic: Homocysteine → 6
• 6 x 1 (Type 1) = 6 (B6)
• 6 x 2 (Type 2) = 12 (B12)

• Mnemonic for biotin:
• ABC PAPify
• ABC - ATP, BIOTIN, CO2 FOR CARBOXYLATION
• When depressed (depression) due to alopecia (), dermatitis () and rash → exercise cause fatigue and eat egg (avidin in egg white inhibits B7)
• Bought a cat → Tom cat → Peed everywhere → Tom cat urine odour () in multiple carboxylase enzyme deficiency ()

• Hari - SSLC (SLC) kku padichapo "Ente monne pee-chi blue aayi!

• Doctor paranju Hartnup aanennu! Tryptophan escape aakunnu apparently!"

• Mutation
• SLC6A19 mutation (Chr.5)
• Transporter is in enterocytes and PCT cells.
• Defect:
• defective Neutral AA transporter
• defective tryptophan transporter
  ↓
  ↓ Tryptophan absorption from the intestine and reabsorption in the kidney
  ↓
  
↓ Tryptophan
↓ Serotonin
↓ Niacin = Niacin deficiency = Pellagra like rash
indoxyl compounds in intestine
↓

Blue diaper syndrome - Due to indican (indoxyl sulfate) in urine
↓
Obermeyer test (indoxyl in urine)

• ↓ Tryptophan → ↓ Serotonin & ↓ Niacin
• (60 mg tryptophan → 1 mg niacin)

• Clinical Features
• Asymptomatic (mostly)
• Cutaneous photosensitivity (m/c symptom)
• Accumulation of tryptophan in intestine → bacterial decomposition → indoxyl compounds → Indoles absorbed → excreted in urine as → bluish discoloration of diaper
• Ataxia
• Wide-based gait

• Test
• Obermeyer test
• indoxyl in urine
• Diagnosis:
• HPLC
• Neutral aminoaciduria

• Treatment
• Niacin, high protein diet
• Lipid soluble tryptophan esters

• Enzyme deficient: Branched chain Alpha-ketoacid dehydrogenase

• Autosomal recessive

• Boxing, cyclic movements and seizures in new-born

• Amino Acids: Leucine, Isoleucine, Valine

• Urine odor:
• Maple syrup or Burnt sugar

• Diagnostic tests are employed:
• FeCl3 test +ve
• DNPH test +ve
• Ketone bodies in urine

• Treatment:
• Restrict Valine, Leucine, Isoleucine in diet
• (Branched chain AA)
• Branch → VaLI
• Thiamine supplementation.

• Mnemonic Miss u di (MSUD )- Batch (Branch) mate valli

• Maple () tree has Branches () and VALi () → got in Cycle (Cyclical movements)

• Gotcha → Glucose thinnuna β guy → Got him → Beat his tummy so badly (Liver damage → hepatomegaly) → Break bones (bone pain, bone erosioins), let him bleed (pancytopenia) → churutti kuutti (crumbled tissue paper) flaskil itt (Erlen flask)

• Most common LSD in children

• Enzyme: Glucocerebrosidase
• Mnemonic: Gau Glu → Gauze Tissue paper → Put in a flask

• Accumulated lipid:
• Glucosyl ceramide/Glucosyl cerebroside.
• Found in RBC and platelet membranes.

• Absence of Beta Glucosidase (Beta Glucosyl Cerebrosidase).
• Cerebroside - Glucose = Ceramide
• Hepatosplenomegaly
• occurs from extramedullary erythropoiesis.
• Compensatory erythropoiesis causes:
• Bony erosions and bone pain.
• Osteopenia
• Potential Erlenmeyer flask deformity.

• Pancytopenia
• Macrophages engulf abnormal RBCs and platelets
• Leads to refractory anemia and thrombocytopenia
• Macrophages
• Accumulate fibrils
• Leads to crumpled tissue paper cells
• on bone marrow biopsy

• No mental retardation.

• No cherry red spot.

• Enzyme replacement therapy is available.
• α and β Glucosidase deficiency

Cherry Red Spot Disorders

• Seen in:
• GM1 gangliosidosis
• Tay-Sachs disease
• Niemann Pick disease

 

• Not seen in Gaucher

Mucopolysaccharidosis (MPS)

Mnemonic:

• All present → Hurler

• Normal intelligence
• Mo () Mo () shie ()
1. She → No MR → But Hirsuitism → DS
• Ass → Idurunidase
2. Martolamy → Like She → No MR, No Hirsuitism → DS
• Mola (Morattu Lamy) → Arya Stark (Aryl sulfatase)
• Has Nagam (Nagalzyme) around her
3. More Que →Four Que
• No visceromegaly
• Only 1 without Visceromegaly
• No Leucocyte inclusions
• Only 1 without Leucocyte inclusions

• Clear vision
• Hunters and Filippines (San filippo) are similar
1. Hunters
• aggressively (Aggressive behavious)
• aim for the X (X-linked recessive).
• Hunter ate → Iduronate
• Pebbly skin
2. Filippines
• more common
• But not a common answer

• Hydrops fetalis only in
• Sly

• HHHH → Hunter, Hurler, Heparan sulphate

Confirmatory Tests

• Enzyme Activity Assay
• In leukocytes or fibroblasts

• Genetic tests

Prenatal Diagnosis

• Amniocentesis/CVS
• For enzyme assay or gene testing

Inheritance:

• All AR
• except Hunter (X-linked)
• Fabry Mnemonic: X-linked

Clinical of Hurler:

• Coarse facies, hepatosplenomegaly
• puffy-looking facies,
• periorbital puffiness,
• depressed nose bridge,
• prominent philtrum,
• protruding tongue

• Intellectual disability/mental retardation

• Dysostosis multiplex
• Thickened skull
• J-shaped sella
• Paddle ribs
• Bullet phalanges





 
• Vertebral beaking

• Corneal clouding

• Cardiac issues,

• Airway obstruction

Aryl suphatase

• Metachromatic leukodystrophy
• Enzyme: Arylsulfatase A
• CNS involvement present

• Maroteaux-Lamy
• Enzyme: Arylsulfatase B
• No CNS involvement