Which of the following diseases have autosomal recessive inheritance?

Explanation

## Correct Answer: B. Albinism Albinism is the paradigm autosomal recessive disorder in medical genetics. It results from mutations in genes encoding enzymes involved in melanin synthesis (most commonly TYR gene encoding tyrosinase). Both parents must be heterozygous carriers for an affected child to manifest the disease (25% risk per pregnancy). The condition presents with complete or partial absence of melanin pigment in skin, hair, and eyes, leading to characteristic clinical features: hypopigmentation, photophobia, nystagmus, and significantly increased risk of skin malignancy (squamous cell carcinoma, melanoma) in Indian populations with high sun exposure. The inheritance pattern is **autosomal** (not X-linked) and **recessive** (requires two mutant alleles). This makes albinism the textbook example for autosomal recessive inheritance taught in all Indian medical curricula and is a high-yield concept for NEET PG genetics questions. ## Why the other options are wrong **A. Marfan's syndrome** — Marfan syndrome is **autosomal dominant**, not recessive. It is caused by mutations in the FBN1 gene encoding fibrillin-1, a structural protein. Affected individuals have a 50% risk of passing the mutation to offspring. The classic triad includes skeletal abnormalities (tall stature, arachnodactyly, pectus deformity), ocular lens dislocation (ectopia lentis), and cardiovascular complications (aortic root dilatation, dissection). NBE often pairs Marfan with recessive inheritance to test whether students confuse dominant and recessive patterns. **C. G6PD deficiency** — G6PD deficiency is **X-linked recessive**, not autosomal recessive. The G6PD gene is located on the X chromosome. Males are predominantly affected (hemizygous); females are usually carriers but can manifest disease if homozygous or due to skewed X-inactivation. Clinically, it presents with acute hemolytic episodes triggered by oxidative stress (fava beans, sulfonamides, aspirin, infections). This is endemic in India, particularly in tribal populations and Mediterranean regions, making it a common NEET PG trap when testing inheritance patterns. **D. Lesch-Nyhan syndrome** — Lesch-Nyhan syndrome is **X-linked recessive**, caused by deficiency of the enzyme HGPRT (hypoxanthine-guanine phosphoribosyl transferase). Males are affected; females are carriers. The condition presents with severe gout, uric acid nephrolithiasis, neurological manifestations (choreoathetosis, spasticity, intellectual disability), and characteristic self-injurious behavior (biting lips and fingers). The X-linked inheritance pattern is the key discriminator; students may confuse it with autosomal recessive disorders if they focus only on the severity and rarity of the disease. ## High-Yield Facts - **Albinism** is the classic **autosomal recessive** disorder; both parents must be carriers (Aa × Aa → 25% affected). - **Tyrosinase deficiency** (TYR gene mutation) is the most common cause of oculocutaneous albinism (OCA1) in Indian populations. - **Marfan syndrome** is autosomal **dominant** (FBN1 gene); **G6PD deficiency** and **Lesch-Nyhan syndrome** are both **X-linked recessive**. - Albinism carriers (heterozygotes) are clinically **unaffected** but have 50% risk of transmitting the allele to offspring. - Indian albino patients have **markedly elevated skin cancer risk** due to high UV exposure; sun protection and regular dermatological surveillance are essential. ## Mnemonics **ARR (Autosomal Recessive Rarity)** **A**lbinism, **R**ecessive polycystic kidney disease, **R**ecessive spinal muscular atrophy. Use this to anchor the most common autosomal recessive disorders when inheritance pattern questions arise. **X-linked Trap: GGL** **G**6PD deficiency, **G**aucher disease (can be AR or AR), **L**esch-Nyhan. When you see hemolytic anemia or gout in a male, think X-linked first before assuming autosomal recessive. ## NBE Trap NBE frequently pairs Marfan syndrome (autosomal dominant) with albinism in inheritance questions to test whether students can distinguish dominant from recessive patterns. The trap is that both are rare genetic disorders, leading students to incorrectly assume rarity = recessive inheritance. ## Clinical Pearl In Indian dermatology practice, albino patients present with severe photosensitivity and require aggressive sun protection (SPF >50, protective clothing). Early recognition of albinism in newborns (pale skin, light-colored hair despite dark-skinned parents) allows counseling of both parents as obligate carriers and genetic risk assessment for siblings. _Reference: Robbins Ch. 5 (Genetic Disorders); Harrison Ch. 87 (Genetic Principles); KD Tripathi Ch. 2 (Genetics and Molecular Biology)_