Genetic And Metabolic Disorders Flashcards
A newborn baby is born to non-consanguineous parents. She is noted to have puffy feet on her 1st day check. She weighs 2.0 kg with widely spaced nipples and absent femoral pulses. You have asked your registrar to review her as you think she may have Turner’s syndrome. She agrees and asks you to send blood tests for karyotyping. Which is the chromosomal diagnosis of Turner’s syndrome?
A. 47XXY
B. 45YO
C. 46XY
D. 46XX
E. 45XO
E. 45XO
1 E Turner’s syndrome is due to the absence of two sex chromosomes (pair number 23). Therefore the child is a girl (due to the absence of the Y chromosome) and has only 45 chromosomes. The physical characteristics may be noted at birth, particularly lymphoedema and cardiac anomalies, or noted later in life, such as short stature, delayed puberty, thyroid disorders, coarcation of aorta, aortic stenosis, horseshoe kidney and coeliac disease. (C) and (D) are normal gentoypes for males and females respectively. (A) is the karyotype of Klinefelter’s syndrome which presents in boys with tall stature, delayed puberty and gynaecomastia.
A 15-year-old boy was diagnosed with Down’s syndrome at birth. He is short for his age, had cardiac surgery as a baby, has treatment for hypothyroidism and now attends mainstream school with some support. His parents are enquiring now about what complications he faces. Which of these is not a recognized complication of Down’s syndrome?
A. Retinoblastoma
B. Atrioventricular septal defect (AVSD)
C. Type 1 diabetes
D. Leukaemia
E. Alzheimer’s disease
A. Retinoblastoma
2 ADown’s syndrome affects many systems. Cardiac: ventricular septal defect,
AVSD (B) and Tetralogy of Fallot. Endocrine: hypothyroidism, Addisons disease, type 1 diabetes (C). Ocular: cataracts, but not retinoblastoma (A). Malignancy: leukaemia (D). Gastrointestinal: duodenal atresia, Hirschprung’s disease. Musculoskeletal: atlanto-axial instability. They are also at risk of Alzheimer’s dementia (E) in later life.
A baby is born and you are asked to do the baby check at 6 hours post-natal age. You go to see the baby and mum states that he has not yet had a feed. You advise they stay in hospital until the feeding is established. This is the first child of non-consanguineous parents. On day 4 when you review the baby he has still not had an adequate intake, has lost over 10 per cent in birth weight and is markedly hypotonic. Your consultant asks you to request genetic testing for Prader–Will syndrome. What is the inheritance of Prader–Willi syndrome?
A. X-linked
B. Imprinting
C. Monosomy
D. Microdeletion
E. Trisomy
B. Imprinting
3 B Prader–Willi syndrome is inherited by the phenomenon of genetic imprinting (B). It is due to the fact that for some chromosomes, you need the paternal or maternal chromosome to be present for normal functioning. To inherit Prader–Willi syndrome, there is loss of part of the paternal chromosome 15. X-linked conditions include Duchenne’s muscular dystrophy, Fragile X syndrome (A) monosomy is seen in Turner’s syndrome with only one X chromosome in girls (C), microdeletions cause DiGeorge’s syndrome and Williams’ syndrome (D) and trisomy 21, 13 and 18 are seen in Down’s, Patau’s and Edwards’ syndromes, respectively (E).
A 5-day-old baby who is formula fed is on the neonatal unit being treated for sepsis secondary to an Escherichia coli urinary tract infection. He has been on antibiotics for 5 days. He is still unwell and vomiting. The parents are consanguineous and this is their first child. He has had repeat blood and urine cultures taken. Urine reducing substances are positive. What is the most likely underlying diagnosis?
A. Fructose intolerance
B. Galactosaemia
C. Phenylketonuria
D. Lactose intolerance
E. Glycogen storage disease
B. Galactosaemia
4 B Galactosaemia (B) is due to a deficiency in galactose-1-phosphate uridyl transferase. It results in illness with lactose-containing milks, with vomiting, cataracts and recurrent episodes of Escherichia coli sepsis. Fructose intolerance (A) can also produce a metabolic acidosis and vomiting, but is distinguished from galactosaemia by the E. coli sepsis. Phenylketonuria (C) presents with developmental delay when the child is older and a musty smelling urine, not acute illness and sepsis. Lactose intolerance (D) is unlikely as lactase levels are usually high at birth and may present with diarrhoea and poor weight gain. Glycogen storage diseases (E) are a heterogeneous group of disorders that present with liver, muscle and cardiac defects.
A 10-year-old boy is brought to the GP with tall stature. He is taller than his peers at school. His arm span is greater than his height, he has long, thin fingers, scoliosis and pectus excavatum. He is also concerned that he gets short of breath at school during PE lessons. You refer him for an echocardiogram and chest x-ray. You make a clinical diagnosis of Marfan’s syndrome. What is the inheritance of Marfan’s syndrome?
A. X-linked recessive
B. Autosomal recessive
C. Sporadic
D. X-linked dominant
E. Autosomal dominant
E. Autosomal dominant
5 E Marfan’s syndrome is an autosomal dominant (E) condition affecting the fibrillin gene. It is a connective tissue disorder that affects the musculoskeletal, ocular and cardiac systems. X-linked conditions affecting the musculoskeletal system include Duchenne’s and Becker’s muscular dystrophy, which can present with muscle weakness or delayed motor milestones (A). Autosomal recessive conditions affecting the musculoskeletal system include homocysteinuria, which has similar skeletal characteristics but also thromboembolic tendency (B). Klinefelter’s syndrome is sporadic and can present with tall stature (C). Hypophosphataemic rickets is an X-linked dominant condition, which can present with genu varum and short stature (D).
A pregnant woman seeks advice from you regarding her condition and its impact on the pregnancy and risk to the baby. She has phenylketonuria (PKU) and has been on a phenylalanine-free diet for life. She was told that it was very important during her pregnancy to be compliant with this diet. She would like to know how the baby will be tested for the condition as she is aware that is an inherited condition. What is the initial investigation you will advise?
A. Serum tyrosine levels
B. Genetic screening
C. Serum phenylalanine levels
D. Urine phenylketones
E. Newborn blood spot screening
E. Newborn blood spot screening
6 E PKU is an autosomal recessive metabolic condition resulting in a defect in enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine. Due to the accumulation of phenylalanine and conversion to phenylketones, unrecognized and untreated PKU can result in seizures and musty smelling urine and eventually microcephaly and learning difficulties. PKU is screened on the newborn blood spot screening test (E). It is a rare but treatable condition with a good prognosis if management is started from birth (phenylalanine-free diet for life). (A), (C) and (D) can be measured but not usually as the diagnostic test, but they can be useful for monitoring of treatment. (B) is not performed routinely for PKU.
You see an 18-year-old boy who is the first child of his African parents and was born in Kenya before moving to the UK 1 year ago. He has white skin and pink irises. He was diagnosed with oculocutaneous albinism at birth. He has difficulty with his sight but has recently developed a skin lesion on his face. His mother has brought him to his GP as it has recently started to increase in size. On examination you note is an elevated, 3 cm diameter lump on the left of his nose. It has irregular edges, is firm and immobile and pigmented in areas. What is the likely diagnosis?
A. Benign naevus
B. Scar from a healing wound
C. Malignant tumour
D. Abscess
E. Wart
C. Malignant tumour
7 CThis boy has oculocutaneous albinism, a metabolic condition affecting the production of skin pigment melanin. He is therefore at higher risk of skin malignancy (C) due to the lack of melanin. There is no history of trauma (B) or infection or fever (D) so both are less likely. Benign naevus or mole (A) would be static in size, smooth and regular edged in comparison to a malignant tumour. Warts caused by human papilloma virus (E) may be in the differential diagnosis but are rarely located on the face. With the medical background of albinism, (C) is more likely.
A 20-month-old boy has been referred due to delayed walking. On further questioning you establish he has no difficulty feeding, had head control at 3 months of age, and sat up by 8 months. He has been crawling for the last 8 months, but he does not pull to stand or walk with support. He has no dysmorphic features. There is no known family history of muscle problems. His mother has no myotonia. His mother is very concerned and asks you what is wrong. What is the most likely diagnosis?
A. Myotonic dystrophy
B. Duchenne’s muscular dystrophy
C. Down’s syndrome
D. Myasthenia gravis
E. Becker’s muscular dystrophy
B. Duchenne’s muscular dystrophy
8 B Delayed walking is a common paediatric presentation. Of the causes listed,
Duchenne’s muscular dystrophy (B) is the most common, with Becker’s muscular dystrophy (E) being less severe but a similar presentation. Both are due to defects in the dystrophin gene and are inherited in an X-linked
manner. Myotonic dystrophy (autosomal dominant) (A) and Down’s syndrome (C) may present with hypotonia from birth, both centrally and peripherally, though children with Down’s syndrome may have other features including dysmorphic facies (low set ears, epicanthic folds, protruding tongue, flattened nasal bridge), single palmar crease, sandal gap toes. Myasthenia gravis (D) can present with delayed walking, but fatigability is a key sign that differentiates it from the others.
You are asked to see a 3-day-old baby on the post-natal ward. The baby was born at term and is the first child of consanguineous parents. The baby is drowsy and vomiting, with no fever, rash or diarrhoea. On examination, the baby is noted to have ambiguous genitalia. You do some blood tests: white cell count 5 × 109/L, C-reactive protein 2 mg/L, Na+ 125 mmol/L, K+ 8 mmol/L, glucose 1.7 mmol/L. 17-OH level progesterone is low. You make a diagnosis of congenital adrenal hyperplasia. What is the best initial management plan?
A. IV hydrocortisone
B. IV dextrose
C. IV dextrose and IV hydrocortisone
D. IV 0.9 per cent saline
E. IV 3 per cent saline and IV hydrocortisone
C. IV dextrose and IV hydrocortisone
9 CCongenital adrenal hyperplasia is due to a deficiency of the enzymes that metabolize sex hormones (testosterones) to cortisol. Hence the accumulation of sex hormones can result in masculinized female genitalia or abnormal male genitalia. The lack of cortisol presents as a salt-losing crisis, as in this child, with low glucose and vomiting. Replacement of glucose and steroids is required in the first instance (C); they are both of high priority, so not (A) or (B). This will help to correct the electrolyte imbalances. Sodium disturbance should generally not be corrected too quickly; therefore (E) is incorrect. Normal saline (0.9 per cent) alone will not help, although may be required if there is hypotension.
A 10-year-old boy is brought to the paediatric outpatient department for a review of his height. He was found to be on the 0.4th centile and his mid-parental height is the 98th centile. He also has widely spaced nipples, wide carrying angle, hypogonadism, pulmonary stenosis and developmental delay. What is the most likely diagnosis?
A. Angelman’s syndrome
B. Williams’s syndrome
C. Turner’s syndrome
D. Prader–Willi syndrome
E. Noonan’s syndrome
E. Noonan’s syndrome
10 E Noonan’s syndrome has a similar phenotype to Turner’s syndrome but can present in both girls and boys (unlike Turner’s syndrome which only occurs in girls (C)). These features are not typical of the other syndromes: (A) developmental delay and happy demeanour, (B) typical facial features, aortic stenosis, developmental delay, (D) poor feeding and weight gain in the neonatal period, followed by overeating in later life and obesity.
