Lesch Nyhan Syndrome, Orotic Aciduria, Pellagra Case Studies

Lesch Nyhan Syndrome

Case 1: Boy Complaining Of Joint Pain

A mother came to OPD with a 12 years old mentally retarded boy complaining of joint pain, an irresistible urge to bite his fingers and lips. The serum uric acid level was found to be elevated.

• Diagnosis– Lesch Nyhan syndrome.
• Deficient enzyme– HGPRTase.
• Partial deficiency of HGPRTase leads to the Kelley-Seegmiller syndrome.
• The pathway involved is– Purine salvage pathway.

Read And Learn More: Biochemistry Clinical Case Studies With Answers

Lesch Nyhan Syndrome

• X-Linked recessive disorder.
• Affects only males.
• Complete deficiency of Hypoxanthine Guanine phosphoribosyl Transferase.
• It is characterized by mental retardation, aggression, and self-destructive behavior (lip and finger biting).
• Neurological symptoms are thought to be due to decreased availability of purines to the developing brain which has a low capacity for de novo purine synthesis and hence depends on the purine salvage pathway for the supply of purine nucleotides.

Hyperuricemia in Lesch-Nyhan Syndrome

• A deficiency of HGPRTase causes the accumulation of PRPP. PRPP is a substrate for de novo synthesis of nucleotides. Also, hypoxanthine and guanine are converted into uric acid.
• Since high urate levels are present in the blood, individuals with this condition are also prone to develop gout and kidney stones.

Case 2

A 4-year-old boy complains of joint pain, aggressive behavior, a learning disability, and urge to bite his own fingers and lips. His serum uric acid is above normal.

1. Name the disorder and enzyme defect.
2. Draw the reaction catalyzed.

Question 1. What is the normal uric acid level and explain the cause of hyperuricemia observed above.
Answer:

1. The normal level of Uric acid.
2. In males– 3–7 mg/dl.
3. In female– 2–5 mg/dl.

Case 3

A boy has developed a tendency of biting nails, fingers, and lips, often causing self-mutilation. He also suffers from spasticity and mental retardation.

Question 1. Explain why only males are affected by the disease.
Answer: It is an X-linked recessive disorder.

Orotic Aciduria

Case 1: Severe Anemia And Failure To Thrive

A 6 years old girl presented to the clinic with severe anemia and failure to thrive. The urine was positive for the presence of orotate crystals.

• Diagnosis– Orotic aciduria.
• The pathway involved– Pyrimidine synthesis.

Two types:

Type 1 and Type 2.

Deficient Enzymes

1. Orotate phosphoribosyl Transferase.
2. Orotidylate decarboxylase.

Orotic aciduria

1. Autosomal recessive.
2. Clinical Features
3. Orotic acid crystalluria.
4. Failure to thrive.
5. Megaloblastic anaemia.
6. Immunodeficiency.
7. Remission with oral uridine.
8. It is a defect in pyrimidine synthesis.

Case 2: Megaloblastic Changes In RBCs

A 12-year-old child was chronically ill with anemia, repeated infections, and diarrhea from the age of 3 months. Laboratory investigations showed megaloblastic changes in RBCs on marrow examination. Folic acid and Vitamin B12 were given but did not improve. Also, there is no response to Iron, Vitamin C, and pyridoxine. Crystals of orotic acid were isolated from the urine of the patient.

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

Pellagra

Case 1: Diarrhoea, Loss Of Memory

A 7-year-old child was brought to the hospital with complaints of diarrhea, loss of memory, and necklace-shaped rash around the neck.

• In dietary history, they took predominantly jowar and maize in their diet.
• Diagnosis– Pellagra.
• Deficient vitamin– Niacin.
• Active form– NAD+, NADP+.

Pellagra Important Reactions: Oxidation-Reduction reactions in carbohydrate, lipid, and protein metabolism.

Question 1. Glyceraldehyde 3 phosphate dehydrogenase.
Answer: Glyceraldehyde 3 phosphate———> 2,3 bisphosphoglycerate

Question 2. Pyruvate dehydrogenase.
Answer: Pyruvate ———> acetyl CoA.

Pellagra Deficiency Manifestation

4Ds

1. Diarrhea.
2. Dementia.
3. Dermatitis.
4. Death if untreated.

Jowar has high leucine content which inhibits QPRT (Quinolinate phosphoribosyl transferase) in tryptophan to niacin conversion. In maize, niacin is available in bound form, so not available to utilize by the body.