Maple Syrup Urine Disease, Urea Cycle Disorders, Gout Case Studies

Maple Syrup Urine Disease, Parkinson’s Disease, Hartnup’s Disease

Maple Syrup Urine Disease

• Metabolic defect of branched-chain amino acids (valine, leucine, and isoleucine).
• Defect– branched-chain alpha-keto acid dehydrogenase.
• Clinical symptoms– urine of the affected individual smells like maple syrup or burnt sugar, mental retardation, convulsions, and death within one year after birth.
• Diagnosis– by tandem mass spectrometry.
• Treatment– low branched-chain amino acids in the diet.

Read And Learn More: Biochemistry Clinical Case Studies With Answers

Case 1: Seizures, Not Accepting Feeds, And Excessive Crying

A neonate was brought to the emergency department with seizures, not accepting feeds and excessive crying. The plasma amino acid profile revealed elevated valine, isoleucine, and leucine. The urine of the neonate smells like burnt sugar.

Question 1. What is a probable diagnosis?
Answer: Maple syrup urine disease.

Parkinson’s Disease

• Affecting elderly people, the incidence is 1% above the age of 60 years.
• It is due to degeneration of the substantia nigra and locus ceruleus of the brain leading to a decrease in dopamine synthesis.
• Clinical features– tremors, mask-like face, rigidity, involuntary movements, lethargy, etc.
• Treatment– L-DOPA and carbidopa.
• Dopamine does not cross the blood-brain barrier hence DOPA is given, which is converted into dopamine in the brain, and peripheral conversion is blocked by DOPA analog (carbidopa).

Hartnup’s Disease

• It is due to impaired transport of tryptophan and other neutral amino acids in the intestine, renal tubules, and brain.
• Clinical features– dermatitis, ataxia, mental retardation, pellagra-like symptoms.

Urea Cycle Disorders

These are genetic diseases caused due to a deficiency of enzymes in the urea cycle.

These enzymes are responsible for removing ammonia from the blood. A deficiency of any enzyme leads to the elevation of ammonia and its toxic effects.

Question 1. Why ammonia is toxic to the brain?
Answer:

Case 1: Hepatosplenomegaly, Convulsion, Respiratory Failure, And Coma

A 3-month-old infant, a product of consanguineous marriage developed poor feeding, hepatosplenomegaly, convulsion, respiratory failure, and coma on day 9 after birth. NH3 level was found raised; Blood shows increased levels of arginosuccinic acid.

Question 1. What is your probable diagnosis?
Answer: Arginosuccinic aciduria.

Case 2:History Of Lethargy, Poor Feeding, And Seizures

A male infant with a history of lethargy, poor feeding, and seizures was brought to the hospital. Blood shows increased levels of citrulline and ammonia.

Question 1. What is your probable diagnosis?
Answer: Citrullinemia.

Gout

Case 1: Severe Pain In His Great Toe

A 46 years old man, a chronic alcoholic, and smoker, came to the hospital with a complaint of severe pain in his great toe. On examination, his first metatarsophalangeal joint was inflamed. He had a history of similar episodes in the past.

• Laboratory investigation shows an increased level of Serum uric acid (10 mg/dl). Probable diagnosis– Gout.
• Podagra gout– tophus deposit in 1st metatarsophalangeal joint.
• Confirmatory test– aspiration of urate crystals from joint and microscopic examination negatively birefringent urate crystals.
• Drug of choice– Allopurinol (Competitive and Suicide Inhibitor of Xanthine oxidase), decreases uric acid levels.
• Other drugs– Colchicine, NSAIDs- Reduce inflammation and pain.

Types of Gout

1. Primary
2. Secondary

Causes of Primary Gout (Enzymes involved or biochemical basis of Gout)

1. Increased activity of PRPP synthetase.
2. Increased activity of PRPP Glutamyl amidotransferase.
3. Decreased activity of HGPRTase.
4. Decreased activity of Glucose-6-phosphatase.
5. Increased activity of Glutathione reductase.

Causes of Secondary Gout: Psoriasis, Leukaemia, Lymphoma, Cancer therapy, Renal failure, etc.

Most Common Joint Involved: First metatarsophalangeal joint (great toe).

The normal level of Uric acid

• In males– 3–7 mg/dl.
• In female– 2–5 mg/dl.
• Reason for increased uric acid in von Gierke’s disease.

Due to a deficiency of Glucose-6-phosphatase, Glucose-6-phosphate is diverted to the HMP shunt and the production of ribose increases. Ribose-5-phosphate is a precursor for Purine synthesis. Uric acid is the end product of Purine metabolism.

Case 2:Severe Pain In His Right Leg, Toe, And Knee Joint

A 42-year-old male presented with a complaint of severe pain in his right leg, toe, and knee joint. Laboratory analysis revealed elevated serum uric acid levels.

Question 1. Name the metabolism affected.
Answer: Purine nucleotide metabolism.

Case 3: Painful And Swollen Joints

A 16-year-old male patient presents with complaints of painful and swollen joints. Laboratory report revealed a serum uric acid level of 14 mg/dl.

Mechanism of Drug Action

Allopurinol

1. Competitive inhibitor of Xanthine oxidase.
2. Suicide inhibition– allopurinol is converted into alloxanthine by xanthine oxidase and alloxanthine is a more potent inhibitor of xanthine oxidase. Here enzyme itself increases the potency of the inhibitor