**Question:** Mutation in Hartnup's disease is

A. a deficiency of nicotinamide N-methyltransferase
B. a deficiency of pterin transporter
C. a deficiency of nicotinamide phosphoribosyl-pyrophosphate synthetase
D. a deficiency of tryptophan hydroxylase

**Core Concept:**
Hartnup's disease is a rare autosomal recessive disorder characterized by impaired amino acid transport across the intestinal epithelium and the skin. It is caused by mutations in the SLC46A1 gene, which encodes for the pterin carrier protein involved in the transport of pterins across the membrane. Pterins are essential for the synthesis of folate and tetrahydrobiopterin, which are crucial for various physiological processes, including neurotransmitter synthesis, immune response, and antioxidant defense.

**Why the Correct Answer is Right:**
Hartnup's disease is primarily caused by mutations in the SLC46A1 gene resulting in a deficiency of the pterin transporter. This leads to impaired transport of pterins across the intestinal epithelium and the skin, causing the characteristic symptoms of the disease. The correct answer (B) refers to the deficiency of the pterin transporter, which is crucial for pterin transport across cell membranes.

**Why Each Wrong Option is Incorrect:**

A. Nicotinamide N-methyl-transerase (NNT) deficiency is not directly related to Hartnup's disease, which is caused by pterin transport defect. Nicotinamide N-methyl-transerase is involved in the synthesis of nicotinamide adenine dinucleotide phosphate (NADPH), a key enzyme in the pentose phosphate pathway for glucose and nucleotide synthesis.

C. Nicotinamide phosphoribosyl-pyrophosphate synthetase (NAMPT) deficiency is not involved in the pathogenesis of Hartnup's disease. NAMPT is responsible for the synthesis of nicotinamide mononucleotide (NMN) from nicotinamide riboside and ATP, which is essential for the synthesis of NAD+ and NADP+, important for energy production and antioxidant defense.

D. Tryptophan hydroxylase deficiency (DOPA decarboxylase) is not related to Hartnup's disease. Tryptophan hydroxylase is an enzyme involved in the synthesis of serotonin, dopamine, and norepinephrine, which are crucial neurotransmitters.

**Clinical Pearl:**
Hartnup's disease is a prime example of how mutations in a single gene can lead to clinical syndromes with diverse presentations, such as neurological, psychiatric, and nutritional deficiencies, due to the disruption of pterin transport and subsequent impairments in neurotransmitter synthesis and antioxidant defense.