Genetic, Paediatric and Nutritional Disorders for NEET PG Pathology: Down, Turner, Klinefelter, Storage Diseases, PEU, Vitamins

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🎯 Exam priority: Moderate. Expect: a dysmorphology vignette (Down, Edwards, Patau, Turner, Klinefelter), the enzyme behind a storage disease, the cherry-red spot, fragile X repeats, the classic Wilms presentation, marasmus vs kwashiorkor and the vitamin behind a deficiency picture.

CBME mapping: PA 11.1–11.3, 12.1–12.3. Retinoblastoma and neuroblastoma genetics are in article 4.

Chromosomal disorders, storage diseases and nutritional deficiencies. Drawn by TrackNation.

Chromosomal and Gene Disorders

• Down syndrome: about 95% from nondisjunction (extra, usually maternal, chromosome 21); about 4% from translocation. Risk rises with maternal age (about 1/1476 at 20, 1/352 at 35, 1/85 at 40). Heart disease (VSD, atrioventricular septal defect), duodenal atresia, Hirschsprung disease, coeliac disease, hypothyroidism, leukaemias (ALL, acute megakaryoblastic), atlantoaxial instability and early Alzheimer disease.

• Edwards (trisomy 18): clenched fist with the index finger over the third and fourth, rocker-bottom feet. Patau (trisomy 13): midline defects — holoprosencephaly, cleft lip and palate.

• Turner (45,X): short stature, ovarian dysgenesis with high gonadotropins and infertility, neonatal lymphoedema, webbed neck, coarctation and bicuspid aortic valve.

• Klinefelter (47,XXY): the commonest sex-chromosome disorder — tall, small testes, infertility, high gonadotropins; about 30% get gynaecomastia.

• Fragile X: unstable CGG repeat in FMR1 (normal < 54, premutation 55–200, full > 200) — the commonest inherited cause of intellectual disability and autism.

• Childhood tumours: Wilms tumour presents as a painless abdominal mass; WT1 deletion; WAGR = Wilms, aniridia, genitourinary anomalies. Retinoblastoma presents with leukocoria.

Storage and Metabolic Diseases

• Gaucher: glucocerebrosidase deficiency → glucocerebroside in macrophages (Gaucher cells) → hepatosplenomegaly or CNS disease; treated with enzyme replacement. Niemann-Pick: sphingomyelinase deficiency → sphingomyelin in reticuloendothelial cells. Tay-Sachs: hexosaminidase deficiency → neurodegeneration, cherry-red macular spot, death by about 5; autosomal recessive, carriers 1 in 27 Ashkenazi Jews.

• Mucopolysaccharidoses (e.g. Hurler) are autosomal recessive except MPS II.

• Glycogen storage: von Gierke (GSD I) — severe hypoglycaemia, lactic acidosis, hepatomegaly before age 1; Pompe (GSD II); McArdle (GSD V, muscle phosphorylase) — exercise cramps and rhabdomyolysis.

• Phenylketonuria: phenylalanine hydroxylase deficiency → intellectual disability, mousy odour, lighter skin and hair; lifelong low-phenylalanine diet.

Nutritional Disease

• Marasmus (dry form): severe lack of calories and protein in infants — fat and muscle wasting. Kwashiorkor (wet, oedematous form): older children, often after early weaning when a sibling is born.

• Vitamin A: early night blindness, Bitot spots, xerophthalmia. Vitamin D: rickets (children) and osteomalacia; low calcium drives secondary hyperparathyroidism. Thiamine (B1): beriberi — dry (symmetric stocking-glove neuropathy) and heart failure; Wernicke-Korsakoff in alcohol use. Niacin (B3): pellagra — symmetric photosensitive rash, glossitis, diarrhoea, mental change. Vitamin C: scurvy (article 2).

• Metabolic syndrome: large waist (abdominal fat), hypertension, abnormal fasting glucose or insulin resistance, and dyslipidaemia.

Traps the Examiner Sets

• Most Down syndrome = nondisjunction; translocation in about 4%.

• Turner: coarctation and bicuspid valve; Klinefelter: gynaecomastia and small testes.

• Cherry-red spot = Tay-Sachs (hexosaminidase A).

• Gaucher = glucocerebrosidase; Niemann-Pick = sphingomyelinase.

• Kwashiorkor = oedema, older child; marasmus = wasting, infant.

Memory Hooks & Shortcuts

Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.

• 🧠 Edwards Elects (18) with a clenched fist; Patau Puts holes in the midline (13) — trisomy 18 vs 13

• 🧠 Turner: Two heart Troubles — coarctation, bicuspid — Turner cardiac

• 🧠 Klinefelter: Kinda tall, Kinda breasts, tiny testes — Klinefelter

• 🧠 Cherry on the Tay — Tay-Sachs cherry-red spot

• 🧠 Kwashiorkor = Kwashi-water (oedema) — kwashiorkor vs marasmus

• 🧠 Pellagra's 3 Ds: Dermatitis, Diarrhoea, Dementia — niacin deficiency

Rapid-Revision Cards

• Down mechanism

  ~95% nondisjunction (maternal); ~4% translocation.

• Down risk by age

  1/1476 at 20; 1/352 at 35; 1/85 at 40.

• Down associations

  VSD/AVSD, duodenal atresia, Hirschsprung, leukaemia, early Alzheimer.

• Edwards (18)

  Clenched overlapping fingers, rocker-bottom feet.

• Patau (13)

  Holoprosencephaly, cleft lip/palate.

• Turner (45,X)

  Short, ovarian dysgenesis, webbed neck, coarctation, bicuspid valve.

• Klinefelter (47,XXY)

  Tall, small testes, infertility, gynaecomastia ~30%.

• Fragile X

  FMR1 CGG > 200; commonest inherited ID.

• Wilms

  Painless abdominal mass; WT1; WAGR.

• Gaucher

  Glucocerebrosidase; Gaucher cells; hepatosplenomegaly.

• Niemann-Pick

  Sphingomyelinase.

• Tay-Sachs

  Hexosaminidase; cherry-red spot; AR; death by ~5.

• MPS inheritance

  AR except MPS II.

• von Gierke

  G6Pase; hypoglycaemia, lactic acidosis, hepatomegaly.

• McArdle

  Muscle phosphorylase; exercise cramps.

• PKU

  PAH deficiency; mousy odour; diet.

• Marasmus vs kwashiorkor

  Dry wasting infant vs oedematous older child.

• Vitamin A

  Night blindness, Bitot spots.

• Vitamin D

  Rickets/osteomalacia; ↑ PTH.

• Thiamine

  Beriberi, Wernicke-Korsakoff.

• Niacin

  Pellagra: photosensitive rash, diarrhoea, mental change.

• Metabolic syndrome

  Waist, BP, glucose, lipids.

Sources

Facts in this article were checked against these documents.

• MSD Manual Professional: Down Syndrome; Trisomy 18; Trisomy 13; Turner Syndrome; Klinefelter Syndrome; Fragile X Syndrome; Wilms Tumor — Merck & Co. (MSD Manuals), reviewed 2024–26 (link)

• MSD Manual Professional: Gaucher; Niemann-Pick; Tay-Sachs; Lysosomal Storage Disorders; Glycogen Storage Diseases; Phenylketonuria — Merck & Co. (MSD Manuals), reviewed 2024–26 (link)

• MSD Manual Professional: Protein-Energy Undernutrition; Vitamin A, D, Thiamine and Niacin Deficiency; Metabolic Syndrome — Merck & Co. (MSD Manuals), reviewed 2025–26 (link)

• Competency Based Undergraduate Curriculum, Pathology (PA 11–12) — National Medical Commission, 2024

Test Yourself: Practice Questions

Thirty-two questions in NEET PG style, most of them clinical vignettes.

Practice Questions (NEET PG pattern)

Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.

Q1. Most cases of Down syndrome are caused by

• (a) mosaicism

• (b) maternal nondisjunction giving an extra chromosome 21

• (c) a Robertsonian translocation

• (d) a paternal deletion

Q2. A couple's first child has Down syndrome due to an unbalanced translocation. What share of Down syndrome cases does this mechanism cause?

• (a) about 95%

• (b) none

• (c) about 4%

• (d) about 50%

Q3. The risk of a Down syndrome birth at maternal age 40, compared with 20, is

• (a) slightly lower

• (b) much higher (about 1/85 vs 1/1476)

• (c) lower

• (d) the same

Q4. A newborn with Down syndrome has a congenital obstruction of the upper small bowel. A typical associated anomaly is

• (a) malrotation always

• (b) pyloric stenosis only

• (c) intussusception

• (d) duodenal atresia

Q5. The commonest congenital heart lesions in Down syndrome are

• (a) transposition

• (b) tetralogy only

• (c) coarctation and bicuspid valve

• (d) ventricular and atrioventricular septal defects

Q6. Adults with Down syndrome have an increased risk of

• (a) multiple sclerosis

• (b) Parkinson disease

• (c) Huntington disease

• (d) early-onset Alzheimer disease

Q7. A newborn has a clenched fist with the index finger overlapping the third and fourth fingers and rocker-bottom feet. The karyotype is likely

• (a) 45,X

• (b) trisomy 13 (Patau)

• (c) trisomy 18 (Edwards)

• (d) trisomy 21

Q8. A newborn has holoprosencephaly and cleft lip and palate. The likely diagnosis is

• (a) trisomy 18

• (b) trisomy 13 (Patau)

• (c) fragile X

• (d) Turner syndrome

Q9. A short girl has high FSH and LH, had puffy hands and feet at birth and has a webbed neck. The karyotype is

• (a) trisomy 21

• (b) 47,XXY

• (c) 45,X (Turner syndrome)

• (d) 46,XY

Q10. The cardiac lesions typical of Turner syndrome are

• (a) VSD and AV canal

• (b) coarctation of the aorta and bicuspid aortic valve

• (c) pulmonary stenosis only

• (d) transposition

Q11. A tall infertile man has small firm testes, gynaecomastia and high gonadotropins. The karyotype is

• (a) 47,XXY (Klinefelter)

• (b) trisomy 21

• (c) 45,X

• (d) 46,XX male only

Q12. The commonest sex-chromosome disorder is

• (a) XYY syndrome

• (b) Turner syndrome

• (c) fragile X

• (d) Klinefelter syndrome

Q13. A boy with intellectual disability and autism has more than 200 CGG repeats in FMR1. The diagnosis is

• (a) fragile X syndrome

• (b) Huntington disease

• (c) Down syndrome

• (d) myotonic dystrophy

Q14. The commonest inherited cause of intellectual disability is

• (a) Down syndrome (usually not inherited)

• (b) PKU

• (c) Tay-Sachs

• (d) fragile X syndrome

Q15. A young child has a painless abdominal mass, aniridia and genitourinary anomalies. The syndrome is

• (a) Li-Fraumeni

• (b) WAGR (Wilms tumour with WT1 deletion)

• (c) MEN 2

• (d) neurofibromatosis

Q16. A child has hepatosplenomegaly; marrow shows macrophages laden with glucocerebroside. The enzyme deficient is

• (a) hexosaminidase A

• (b) alpha-L-iduronidase

• (c) glucocerebrosidase (Gaucher disease)

• (d) sphingomyelinase

Q17. Niemann-Pick disease results from deficiency of

• (a) glucocerebrosidase

• (b) sphingomyelinase

• (c) hexosaminidase

• (d) glucose-6-phosphatase

Q18. An infant loses milestones after 6 months, develops seizures, and has a cherry-red macular spot. The enzyme deficient is

• (a) hexosaminidase (Tay-Sachs disease)

• (b) glucocerebrosidase

• (c) phenylalanine hydroxylase

• (d) muscle phosphorylase

Q19. Tay-Sachs disease is inherited as

• (a) autosomal dominant

• (b) autosomal recessive

• (c) X-linked recessive

• (d) mitochondrial

Q20. Which mucopolysaccharidosis is the exception to autosomal recessive inheritance?

• (a) Gaucher

• (b) Tay-Sachs

• (c) MPS I (Hurler)

• (d) MPS II

Q21. An infant has severe fasting hypoglycaemia, lactic acidosis and a big liver. The likely glycogen storage disease and enzyme are

• (a) von Gierke (GSD I) — glucose-6-phosphatase

• (b) Pompe — acid alpha-glucosidase

• (c) McArdle — muscle phosphorylase

• (d) Gaucher — glucocerebrosidase

Q22. A young adult gets muscle cramps and dark urine from rhabdomyolysis after exercise. The likely glycogen storage disease is

• (a) Pompe

• (b) von Gierke

• (c) McArdle disease (GSD V, muscle phosphorylase)

• (d) Tay-Sachs

Q23. An untreated child with intellectual disability, hyperactivity, fair skin and hair and a mousy body odour most likely has

• (a) hypothyroidism

• (b) phenylketonuria (phenylalanine hydroxylase deficiency)

• (c) Tay-Sachs

• (d) Down syndrome

Q24. An infant has severe loss of subcutaneous fat and muscle without oedema. This is

• (a) obesity

• (b) kwashiorkor

• (c) marasmus (dry form)

• (d) rickets

Q25. A 2-year-old weaned early when a sibling was born now has generalised oedema. The form of undernutrition is

• (a) marasmus

• (b) kwashiorkor (wet, oedematous form)

• (c) beriberi

• (d) scurvy

Q26. A child has difficulty seeing in dim light and keratinised patches on the conjunctiva. The deficient vitamin is

• (a) vitamin B1

• (b) vitamin D

• (c) vitamin A

• (d) vitamin C

Q27. Vitamin D deficiency lowers calcium, which leads to

• (a) hypercalcaemia

• (b) low PTH

• (c) high phosphate

• (d) secondary hyperparathyroidism (raised PTH)

Q28. A man with alcohol use disorder develops Wernicke-Korsakoff syndrome. The deficient vitamin is

• (a) vitamin B12

• (b) vitamin A

• (c) niacin (B3)

• (d) thiamine (B1)

Q29. Symmetric burning and numbness of the feet in a stocking-glove pattern from thiamine deficiency is called

• (a) scurvy

• (b) dry beriberi

• (c) wet beriberi

• (d) pellagra

Q30. A patient has a symmetric photosensitive rash on sun-exposed skin, glossitis, diarrhoea and confusion. The deficiency is

• (a) zinc only

• (b) vitamin C

• (c) niacin (pellagra)

• (d) riboflavin

Q31. The components of metabolic syndrome are

• (a) obesity alone

• (b) large waist, hypertension, abnormal fasting glucose or insulin resistance, and dyslipidaemia

• (c) hypertension and gout only

• (d) diabetes and anaemia

Q32. A woman with Turner syndrome had puffy hands and feet at birth. The cause was

• (a) hypothyroidism

• (b) heart failure

• (c) nephrotic syndrome

• (d) lymphoedema

Active Recall

From memory: give the mechanism, risk with maternal age and associations of Down syndrome; distinguish trisomy 18, 13, Turner and Klinefelter; explain fragile X repeats; name the enzyme in Gaucher, Niemann-Pick, Tay-Sachs, von Gierke, McArdle and PKU; contrast marasmus and kwashiorkor; and match vitamins A, D, B1 and B3 to their deficiency diseases.