1. CLINICAL CASES
AMINO ACID METABOLISM
Dr.S.Sethupathy , M.D,Ph.D

2. Case 1

3. • A 28 year old male came with complaints of pain in the right flank , difficulty in
micturition on and off for the past one year.
• He was investigated.
• Urine examination - Albumin and sugar negative
• RBC – numerous ( < 2 RBCs /HPF)
• Pus cells - 9 / hpf ( 0-5 WBCs /hpf)
• Bacteria – nil
• Urine culture – negative
• Urine crystals – Hexagonal crystals

4. USG ABDOMEN – CYSTINE STONES

5. • X- ray – abdomen nothing significant
• Cystine , uric acid stones are radiolucent (
organic)
• Ultrasonogram – Abdomen and pelvis – stones
seen in the renal pelvis
• Urine cyanide- nitroprusside test – positive
Diagnosis - Cystinuria
Defect- Defective transport of amino acids
(COAL) Cystine, ornithine,Arginine, lysine
Except cysteine,others are freely soluble.

6. MANAGEMENT
•Plenty of fluids
•Alkalinization using sodium citrate – metabolized
to sodium bicarbonate
•Restriction of salt and protein
•Lithotripsy
•Nephrolithotomy

7. Case 2

8. •An eight months old baby . The urine, skin of
the baby had musty odour. ( mould odour)
•Baby developed eczema. Seizures on and
off. Skin became fairer.
•Urine routine and metabolic screening tests
were done.
•Urine albumin and sugar negative.

9. URINE MICROSCOPIC EXAMINATION
•RBCs - < 2per hpf (<2)
•WBCs - 3 per hpf (<5)
•Urine crystals - negative
•Urine culture – negative

10. ECZEMA

11. • Ferric chloride test – positive
• Cyanide nitroprusside test – negative
• Dinitrophenyl hydrazine (DNPH) test- negative
• Cetyl trimethyl ammonium bromide(CTAB) test-negative
• Ninhydrin test – positive
• Blood phenyl alanine - 11 mg/dl ( > 4mg/dl)
• Diagnosis - Phenylketonuria
• Defect- Phenylalanine hydroxylase deficiency

12. MANAGEMENT
•Phenyl alanine free diet till 6 years of age
•Phenylketonuric mothers to restrict phenylalanine
during pregnancy
•Autosomal recessive disorder
•Both parents have one abnormal allele
•Genetic counselling

13. Case 3

14. • A 10 days old male infant was brought to the
hospital with complaints of poor feeding,
vomiting for one week, generalized
convulsions and a peculiar burnt sugar smell
from the body and urine.
•Urine routine and metabolic screening tests
were done.
•Urine albumin and sugar negative.

15. URINE EXAMINATION
•Urine Microscopic examaination
•RBCs - < 2per hpf (<2)
•WBCs - 3 per hpf (<5)
•Urine crystals - negative
•Urine culture – negative

16. • Ferric chloride test – Negative
• Cyanide nitroprusside test – negative
• Dinitrophenyl hydrazine (DNPH) test- Positive
• Cetyl trimethyl ammonium bromide(CTAB) test-negative
• Ninhydrin test – positive
• Blood pH - 7.31 ( 7.35 -7.45)
• Bicarbonate – 18 mmol/l ( 22- 29 mmol/l)
• pCO2 - 35 mm of Hg ( 35-45 mm of Hg)
• Metabolic acidosis

17. DIAGNOSIS AND MANAGEMENT
• Plasma total branched chain amino acids- 720 (< 450
miromol/l)
• Maple syrup urine disease – BC alpha keto acid
dehydrogenase deficiency
• Management
• Branched chain amino acids free diet
• High doses of thiamine

18. Case 4

19. •A 9-year-old girl presented with right-
hand dystonia( muscular spasm and
abnormal posture) and gait difficulty.
•She developed blurred vision two years
back and consulted ophthalmologist.
She was found to have lens dislocation
and operated for that.

20. •Later she had a history of severe low back
pain and had right femur fracture.
•There was a family history of undiagnosed
progressive motor disability in her older
brother, which finally resulted in seizure and
death.
•Her parents had consanguineous marriage.

21. •On physical examination, she had fair and wooly
hair and mild fixed oromandibular dystonia
presenting as fixed smiling.
•On chest examination, pectus carinatum (pigeon
chest) was evident.
•At rest, she had dystonic posture in her limbs on
both sides.
•She was unable to stand unsupported
•. Mental retardation

22. SUBLUXATION OF LENS, PECTUS
CARINATUM, DYSTONIA ,
OROMANDIBULAR DYSTONIA

23. SALIENT FEATURES
•Mental retardation
•Charlie Chaplin gait
•Lens dislocation
•Thrombosis
•Cyanide nitroprusside test positive
•Thrombosis

24. • Hb – 14.2 g/dl ( 13.5- 15.5)
• RBC - 4.2 ( 4-6 millions /micro l)
• WBC – 7200 (4500 – 11000 / micro l)
• Platelet - 220000 ( 150000 – 450000 per micro l)
• Blood count normal
• Plasma glucose ( fasting) – 85 mg/dl – Normal
• Serum bilirubin- 0.8 mg/dl (<1 mg/dl)
• AST - 26 U/L ( <40 u/L)
• ALT - 22 U/L ( < 40 U/L)
• ALP - 112 U/L ( 40 – 150 U/L) LFT - normal

25. • TSH - 2.8 ( 0.2 – 5.0 mIU/l)
• T4 - 6.1 (5.0 – 12.0 microg /dl)
• T3 - 135( 80- 220 ng/dl) Thyroid function -
normal
• Serum calcium – 9.8 (9-11 mg /dl) Normal
• Urine Cyanide –nitroprusside test - positive
• Vitamin B12 - 340 ( > 300 pg/ml) normal
• Serum homocysteine - 200 nmol/mL (5 – 15)
•Homocystinuria
•Defect- Cystathionine beta synthase
deficiency

26. FOLIC ACID AND B12
• Homocysteine - COO- CH-CH2 –CH2 –SH
•
• NH2
• Methionine - COO- CH-CH2 –CH2 –S-CH3
•
• NH2
• Methyl THFA-supplies CH3
• B12 carries methyl group

27. • Homocysteine and serine cystathionine
• Cystathionine beta synthase
• Cystathionine to homoserine and cysteine -- co enzyme – B6

28. MANAGEMENT
•Diet low in methionine and rich in cysteine
Adequate doses of
•B12
•Folic acid
•Pyridoxine

29. Case 5

30. • A 47-year-old male with no previous medical history
presents to his family physician complaining of episodic
headaches, sweating, heart palpitations, and a tremor.
• The symptoms started a few years ago, have become
more frequent, and can last anywhere between a few
seconds to an hour.
• The episodes often occur when the patient feels stressed
or exercises.
• He has a family history of hypertension. He does not use
cocaine, methamphetamines drugs.

31. • He has not had fevers, chills, chest pain,
shortness of breath, nausea, vomiting, or
diarrhea.
• Blood pressure - 168/96 mm Hg,
• Height – 170 cm Weight – 72 kg
• BMI – 24.2 ( 18.5- 24.9- healthy Wt)
• RR- 20 breaths per minute
• HR- 116 beats per minute
• Temperature of 98°F (36.66°C).
• CVS and RS - no abnormalities

32. Causes of hypertension
• Renal failure
• Obesity
• Diabetes mellitus
• Hyperthyroidism
• Cushing’s syndrome
• Pheochromocytoma
• Primary hypertension

33. • Serum urea - 24 mg/dl ( 15-40 mg/dl)
• Serum creatinine - 0.9 mg/dl ( 0.6 – 1.2
mg/dl)
• Serum uric acid - 5.2 mg/dl ( 4- 7 mg/dl
• Renal function normal
• TSH - 2.8 ( 0.2 – 5.0 mIU/l)
• T4 - 6.1 (5.0 – 12.0 microg /dl)
• T3 - 135( 80- 220 ng/dl)
Thyroid function – normal
• Plasma glucose F – 86 mg/dl PP - 112
mg/dl

34. ELECTROLYTES
• Serum sodium - 138 (135-145 mmol/l)
• Serum potassium - 4.1 (3.5- 5.0 mmol/l)
• Serum chloride- 98 ( 96-106 mmol/l)
• Serum bicarbonate - 24 ( 22-29 mmol/l)

35. •Urine total metanaphrines - 3350 (<
1300 microg/24 hours)
•Urine metanephrines - 452
(25- 95 microg/24 hours) very high –
epinephrine excess
•Urine normetanephrines - 422 (
75-375 microg/24 hours) slightly
increased –norepinephrine
•It rules out neuroblastoma

36. FALSE POSITIVES
• False positive metanephrine test
• Stress, antidepressants, obstructive sleep apnoea
• Urinary VMA- 23 ( < 8mg/24 hours)
• False positive VMA test
• Avoid chocolate, coffee, tea, and cocoa for 2 to 3 days
before the test is performed.
• Food like citrus fruits, bananas, and food with vanilla.

37. • Diagnosis – Pheochromocytoma
• The triad of headache, palpitations,and
sweating suggest pheochromocytoma
• Elevated urinary metanephrines
• Abdominal CT showed a left adrenal mass ( 3
cm diameter)
• Immunochemistry – Positive for chromogranin
granules
• Pheochromocytoma confirmed

38. Case 6

39. • A 70 years old male came to hospital for the complaints
of resting tremor, slowness of movement, imbalance
which sometimes causes fall and mask like face.
• Diagnosis - Parkinson’s disease
• No diagnostic test useful
• Based on clinical experience of the neurologist, it is
diagnosed.
• Cause- Degeneration of nerve cells of substantia nigra

41. • Parkinsonism- A group of disorders that have symptoms
of Parkinson’s disease and some other symptoms as per
the cause.
• The causes are toxins, drugs, chronic head trauma.
• Dopamine level decreases and causes the symptoms.
• Treatment – Levodopa
• It can cross the blood brain barrier but not dopamine.
• Levodopa gets converted to dopamine in the nerve cells
.

42. •Levodopa is also converted to dopamine in the
intestine , liver and kidney and causes changes in
Glomerular filtration rate, catecholamine release.
•Decarboxylase inhibitors (carbidopa) prevent the
peripheral conversion of levodopa.
•Carbidopa is not able to enter into the CNS. So it
cannot prevent the conversion of l-dopa to
dopamine in the CNS.

43. Case 7

44. • A 6 year old female child was referred to the paediatric
ophthalmologist for low vision evaluation and
management.
• Gross observation revealed child was unable to maintain
eye contact.
• Her sitting position in the school was on 5th bench.
• The child was not paying attention in the study and she
was not writing from the black board in the school.
• Child was very fair skinned out of 3 sibling and her eyes
were moving constantly.

45. •She could not maintain eye contact for long
and her gaze were shifting very rapidly.
•While watching TV she chooses to sit very
close.
•Birth history was normal. No history of
consanguinity or any other sibling suffering
from same problem.

46. EYE PROBLEMS
•Her ocular history revealed no prior eye
examination, ocular surgery and use of low vision
devices. Her medical history was not significant.
•She was diagnosed to have Oculocutaneous
albinism and Nystagmus.
•Nystagmus – rapid involuntary eye movements

47. TYPICAL APPEARANCE OF SKIN, HAIR, LASHES AND EYES OF
PATIENT WITH OCULO-CUTANEOUS ALBINISM

48. •Diagnosis – Oculocutaneous albinism
•Defect –Due to tyrosinase deficiency ,
melanin is not produced
•Management- sun screen , dark goggles

49. Case 8

50. •A three months old baby was brought to the
hospital for the complaint blackening of
napkin.
•Urine was collected and Benedict’s test was
done.
•It was positive ( Black precipitate formed)
•Diagnosis- Alkaptonuria
•Deficiency – Homogentisate oxidase

51. •Complications – at the age of 40-50 ,
develop ochronosis due to the
deposition of alkapton bodies.
•Homogentisic acid is oxidized to
benzoquinone acetate which gets
polymerized to alkapton bodies.

52. ALKAPTONURIA – BLACK URINE

53. OOCHRONOSIS
SKIN

54. DEPOSITION OF ALKAPTON BODIES IN THE SKIN,
CARTILAGE. JOINT, VERTEBRAL DISCS

55. RUPTURE OF ACHILLES TENDON DUE TO
OCHRONOSIS

56. Management
•Physiotherapy
•Pain killer
•Topical hydroquinones
•CO2 laser
•Dermabrasion

57. Case 9

58. • A new born baby with symptoms of poor
feeding, vomiting, lethargy, seizures, and
encephalopathy was treated for infection but
didn’t get improved.
•Suspected hyperammonemia
•Blood ammonia- 52 (15-45 microg/dl)
•Blood urea - 2.2 mg/dl ( 15- 40 mg/dl)
•CSF glutamine - 32 ( 8 – 18 mg/dl)
•Suggestive of hyperammonemia

59. • Arterial Blood pH - 7.52 ( 7.35 -7.45)
• pCO2 - 28 ( 35-45 mm of Hg )
• pO2 - 85 ( 80-100 mm of Hg)
• Bicarbonate - 22 ( 22- 29 mmol/l)
• Respiratory alkalosis
• Serum bilirubin – 0.9 mg/dl (< 1mg/dl)
• AST - 52 U/l ( < 40 u/l)
• ALT - 48 U/l ( < 40 U/l)
• Prothrombin time - 13 sec ( 10-14 sec)
• Not suggestive of liver failure
• Suggestive of defective ammonia metabolism

60. • In case of organic acidemias, blood pH is acidic.
• Here blood pH is alkaline. Organic acidemias ruled out.
• Plasma citrulline level - 7 (< 20 micromol/L) -low
• Urine orotic acid - 13 ( 0-4 years- < 5.0
mmol/mol creatinine, > 5 years old – 1.5
mmol/mol creatinine)
OTC deficiency- Carbomyl phosphate
Urine orotic acid - 1.1
CPS or NAGS deficiency
Hyperammonemia type 2

61. PRINCIPLES OF MANAGEMENT-
•Protein restriction
•Adequate carbohydrate to maintain
normoglycemia
•Anticonvulsants
•Hemodialysis

62. • IV Sodium benzoate administration( Benzoic acid
conjugates with glycine to form hippuric acid ,
which is excreted in urine, Harmless)
• IV phenyl acetate- Conjugates with glutamine to
form phenyl acetyl glutamine)
• IV Arginine given – It stimulates OTC and prevents
valproate toxicity as valproate stimulates CPS-1
and causes hyperammonemia
• Liver transplant

63. Case 10

64. • A 15 year-old boy, a full-term newborn. His development was
normal. Then he developed the skin lesions on the uncovered
parts of the body, face and hands which was severe during summer.
• In a few years, slowly he developed
psychiatric symptoms
such as anxiety, emotional instability,
and mood changes.
• urine examination
• Albumin and sugar – negative

65. • RBCs - < 2per hpf (<2)
• WBCs - 3 per hpf (<5)
• Urine crystals - negative
• Urine culture – negative
• Serum urea - 24 mg/dl ( 15-40 mg/dl)
• Serum creatinine - 0.9 mg/dl ( 0.6 – 1.2 mg/dl)
• Serum uric acid - 5.2 mg/dl ( 4- 7 mg/dl
• Renal function normal
• Plasma glucose F – 86 mg/dl PP - 112 mg/dl

66. • Aminoaciduria- positive
• Urine amino acids chromatography- neutral amino acids
positive
• Urine Obermeyer test - positive
• What is your diagnosis?
• What is the defect ?
• What is the reason for skin changes and psychiatric
symptoms?
• How will you manage?

67. Thank you