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Sciences (clinical)

answer By dr.hayder al-nashmei

1- 46 XY
You cannot cry foul about this one. It is just a simple act of counting and what is more, the chromosomes are numbered. As is traditional, the sex chromosomes at the bottom - the larger X and the smaller Y. This man has hypogonadism and delayed pubertal development. As part of this investigation process one would request a karyotype. The possibilities include Klinefelter's syndrome and Kallmann's syndrome. In this case the karyotype reveals 22 autosomes and XY sex chromosomes 46XY indicating he is a normal male. Therefore, he may have Kallmann's syndrome and his sense of smell should be assessed. Other causes of delayed pubertal development include pituitary lesions like craniopharyngioma, co-morbidities such as severe asthma, or inflammatory bowel disease.

2- 47 XXY
The picture shows gynaecomastia in a patient with a history suggesting Kilinefelter's syndrome. Klinefelter's is characterised by tall stature, small testes, azoospermia and gynaecomastia in a male. Plasma gonadotrophins are raised. Typical karyotype is 47XXY, though mosaics occur with 46XY/47XXY karyotype. There is an increased risk of breast cancer (20 times higher than normal male).

3- Primary hyperparathyroidism
This patient has hypercalcaemia associated with elevated parathyroid hormone (PTH) indicating a diagnosis of primary hyperparathyroidism. The history of breast Ca is a red herring and the bendroflumethiazide although associated with hypercalcaemia would not cause elevated PTH.

4- Potassium infusion
The history describes an episode of collapse in a patient with thyrotoxicosis. The likely cause of the collapse is thyrotoxic hypokalaemic periodic paralysis. Episodes of hypokalaemic periodic paralysis occur in 10% of young Latin American or Asian men with thyrotoxicosis (of whatever aetiology). Acute attacks repond to potassium administration. The periodic paralysis resolves when the thyrotoxicosis is treated.

5- 50% 6- Captopril-induced angioedema

Angiotensin-converting enzyme (ACE) inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin. Patients receiving ACE inhibitors (including captopril) may be subject to a variety of adverse reactions, some of them serious. Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been seen in patients treated with ACE inhibitors, including captopril. Most cases occur within one week of starting therapy. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Emergency therapy, including but not necessarily limited to, subcutaneous administration of a 1:1000 solution of epinephrine should be promptly instituted.

7- Haemophilia B
The pedigree chart shows a pattern of X linked recessive inheritance. Sickle cell disease and thalassaemias are inherited in an autosomal recessive manner; hereditary spherocytosis and von Willebrand's disease are inherited as autosomal dominant diseases. Examples of X linked recessive diseases include Haemophilia A & B Duchenne muscular dystrophy

Becker muscular dystrophy Glucose-6-phosphate dehydrogenase deficiency Lesch-Nyhan syndrome Nephrogenic diabetes insipidus Hunter's syndrome Anderson-Fabry disease Ocular albinism.

8- 100%
The clinical description is that of Leber's hereditary opic neuropathy, one of the first diseases to be aetiologically linked with inheritance of mitochndrial DNA. Mitochodrial DNA is always inherited from the mother and diseases therefore show a distinctive maternal pattern of transmission.

9- 1/120
Cystic fibrosis is inherited as an autosomal recessive disease. In order to have an affected child, the mother and father of 'A' must both be carriers (since they are unaffected by the disease). If the mother is unaffected, the probability of her being a carrier is 2/3. The probability of the father being a carrier is 1/20. The probability of two carriers having a child with CF is 1/4. The probability of the proband (A) being affected is: The probability of the mother being a carrier AND the father being a carrier AND the chance of two carriers having an affected child. If someone has two parents that are each carriers of the CF gene then they have - 1/4 chance of having CF - 2/4 chance of being a carrier - 1/4 chance of not having the gene at all. However we already know that the mother in this case does not have CF. Once that has been discounted there is - 2/3 chance of being a carrier - 1/3 chance of not having the gene at all. Hence the answer is: (Chance of mother being a carrier) x (Chance of father being a carrier) x (Chance of child having CF if both parents are carriers) = 2/3 x 1/20 x 1/4 = 1/120.

10- 100%

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11- 75000

This study shows that annual rate of recurrent subarachnoid haemorrhage is reduced from 10% to 6%. Therefore, if you treated 100 patients for one year you would expect 10 patients with subarachnoid haemorrhage in the medically treated group versus 6 patients in the medical plus radiological intervention group - a reduction of 4 patients per hundred. Therefore you would need to treat 25 patients (4/100) to expect one less case of subarachnoid haemorrhage. Thus the extra cost of this would be 25 x 3000 = 75000.

12- Gaucher disease

The slide shows yellow papules (pingueculae) in the cornea; these are characteristic of Gaucher disease. Gaucher disease is inherited as an autosomal recessive disease. Disease is caused by a deficiency of the enzyme glucocerebrosidase, essentail for the metabolism of glycolipids. There are three types of Gaucher disease:
1. 2. 3. Type 1 Chronic non-neuropathic; adult Gaucher disease Type 2 Acute neuropathic; infantile Gaucher disease Type 3 Subacute neuropathic; juvenile Gaucher disease.

Patients with all types of disease have hepatosplenomegaly and large glucocerebroside-rich cells (Gaucher cells) infiltrating the bone marrow. Type 2 (infantile Gaucher disease) carries the worst prognosis, with children seldom surviving beyond 2 years. Type 1 disease is the commonest, usually presenting in childhood with hepatosplenomegaly, but not uncommonly in middle- or old-age. Bone marrow replacement and hypersplenism result in anaemia and thrombocytopenia. Pathological bone fractures and avascular necrosis of the femoral heads are not uncommon. Bony disease may be confined to the distal ends of the femurs, with formation of characteristic 'Erlenmeyer flask' shaped cysts. The skin may show a grey-brown discolouration, especially around the forehead, hands and pretibial regions. Characteristic yellow or yellow-brown papules (pingueculae) develop at the sclerocorneal junctions.

13- 50%
Hypophosphataemic vitamin D-resistant rickets is inherited in an X linked dominant manner. Offspring of affected mothers, regardless of the children's sex, have a 50% chance of acquiring the gene.