A 6-year-old child is brought to the OPD with a history of mental retardation, failure to walk , failure to grow, seizures, hyperactivity, and tremors. On examination, there is microcephaly, fair hair, light skin color, and blue eyes. Which of the following enzyme is deficient in this child?
**Core Concept**
The child's symptoms are indicative of a genetic disorder affecting neurotransmitter synthesis, leading to neurological and developmental impairment. This condition is associated with a deficiency of an enzyme involved in the biosynthesis of a crucial neurotransmitter.
**Why the Correct Answer is Right**
The child's symptoms, including mental retardation, seizures, hyperactivity, and tremors, are characteristic of Phenylketonuria (PKU). PKU is caused by a deficiency of the enzyme Phenylalanine Hydroxylase (PAH), which is essential for converting the amino acid Phenylalanine (Phe) to Tyrosine (Tyr). Tyrosine is a precursor for the neurotransmitters Dopamine, Norepinephrine, and Epinephrine. The deficiency of PAH leads to an accumulation of Phenylalanine, which is toxic to the developing brain, causing the observed symptoms.
**Why Each Wrong Option is Incorrect**
**Option A:** Homogentisate 1,2-Dioxygenase (HGD) deficiency is associated with Alkaptonuria, a different genetic disorder characterized by dark urine, arthritis, and ochronosis, but not the symptoms described.
**Option B:** Tyrosine Hydroxylase (TH) deficiency is associated with a rare genetic disorder characterized by decreased production of Dopamine, Norepinephrine, and Epinephrine, leading to symptoms such as developmental delay, hypotonia, and seizures, but not the specific combination of symptoms described.
**Option C:** Dihydropteridine Reductase (DHPR) deficiency is associated with a rare genetic disorder characterized by decreased recycling of Tetrahydrobiopterin (BH4), leading to decreased activity of PAH and TH, but the symptoms are more variable and less specific than those described.
**Option D:** This option is blank, so we will ignore it.
**Clinical Pearl / High-Yield Fact**
Early diagnosis and treatment of PKU with a strict Phenylalanine-restricted diet can prevent intellectual disability and other complications, emphasizing the importance of newborn screening programs for this condition.
**Correct Answer:** C. Dihydropteridine Reductase (DHPR) deficiency