Which one of the following is result of inborn error of nucleic acid metabolism?

Question

Accepted Answer

The correct option is 3: Lesch-Nyhan syndrome

Lesch-Nyhan syndrome (LNS) is definitively classified as an inborn error of **nucleic acid metabolism**, specifically involving the purine salvage pathway. The disorder is caused by a profound deficiency of the enzyme Hypoxanthine-Guanine Phosphoribosyltransferase (HPRT), which is critical for recycling purine bases. Purines, namely adenine and guanine, are the foundational nitrogenous bases required for the synthesis of DNA and RNA. The HPRT enzyme normally functions to convert the purine breakdown products hypoxanthine and guanine back into Inosine Monophosphate (IMP) and Guanosine Monophosphate (GMP), respectively, thereby efficiently recycling these vital building blocks. When HPRT is deficient, this salvage pathway fails, leading to two major consequences: a massive overproduction of purines via the *de novo* synthesis pathway to compensate, and the rapid degradation of the excess purine bases into uric acid. The resulting hyperuricemia (excessive uric acid in the blood and urine) is the direct metabolic consequence of this defective purine—a nucleic acid component—recycling mechanism, which is responsible for the classic symptoms of gout, kidney stones, and severe neurological impairment.

The incorrect option is 1: Hartnup disease

Hartnup disease is an inherited disorder that involves a defect in the transport of **amino acids**, not nucleic acids. Specifically, it is caused by a genetic mutation in the *SLC6A19* gene, which is responsible for encoding the neutral amino acid transporter (B0AT1) found in the kidney and small intestine. The primary metabolic error is the malabsorption of neutral amino acids, particularly tryptophan, from the gut and their excessive excretion in the urine. This loss of tryptophan can lead to a deficiency of nicotinamide (Vitamin B3), resulting in pellagra-like skin rashes and neurological symptoms. Thus, the fundamental metabolic error relates to protein building blocks and their transport, not the synthesis or degradation of DNA/RNA components.

The incorrect option is 2: Fabry's disease

Fabry's disease is an X-linked inherited condition categorized as a **lysosomal storage disorder**, meaning it is an error of lipid metabolism. The defect lies with the enzyme alpha-galactosidase A ($\alpha$-GAL A), which is responsible for breaking down a specific fatty substance (a glycosphingolipid) known as globotriaosylceramide (Gb3). Due to the lack of this functional enzyme, Gb3 progressively accumulates within the lysosomes of cells throughout the body, particularly in the blood vessels, heart, and kidneys. This accumulation of lipid material causes the characteristic pain, skin lesions, and organ damage associated with the disease. Therefore, the core metabolic process affected is the catabolism of lipids, completely unrelated to purines, pyrimidines, or nucleic acid metabolism.

The incorrect option is 4: McArdles syndrome

McArdle's syndrome, also known as Glycogen Storage Disease Type V (GSD V), is a disorder of **carbohydrate metabolism**. It is caused by a deficiency of the enzyme muscle glycogen phosphorylase, also called myophosphorylase. This enzyme is essential for the breakdown of glycogen—the storage form of glucose—in muscle tissue to provide energy during exercise. A deficiency means that muscles cannot properly access their stored fuel, leading to exercise intolerance, muscle pain, cramps, and sometimes rhabdomyolysis (muscle breakdown). Since the primary defect involves the storage and breakdown of a complex carbohydrate (glycogen), it is clearly an error of carbohydrate metabolism, not nucleic acid metabolism.