Question 286#

Fragile X is associated with each one of the following, except:

A. Small, firm testes

Correct Answer A:

Fragile X:

Fragile X is a trinucleotide repeat disorder.

Features in males:

• Learning difficulties
• Large low set ears, long thin face, high arched palate
• Macroorchidism
• Hypotonia
• Autism is more common
• Mitral valve prolapse

Features in females (who have one fragile chromosome and one normal X chromosome) range from normal to mild.

Diagnosis:

• Can be made antenatally by chorionic villus sampling or amniocentesis
• Analysis of the number of CGG repeats using restriction endonuclease digestion and Southern blot analysis

Question 287#

When establishing a screening programme, which one of the following is not a key criteria as defined by Wilson and Junger?

A. There should be a recognised latent or early symptomatic stage

Correct Answer E:

Screening: Wilson and Junger criteria:

1. The condition should be an important public health problem
2. There should be an acceptable treatment for patients with recognized disease
3. Facilities for diagnosis and treatment should be available
4. There should be a recognized latent or early symptomatic stage
5. The natural history of the condition, including its development from latent to declared disease should be adequately understood
6. There should be a suitable test or examination
7. The test or examination should be acceptable to the population
8. There should be agreed policy on whom to treat
9. The cost of case-finding (including diagnosis and subsequent treatment of patients) should be economically balanced in relation to the possible expenditure as a whole
10. Case-finding should be a continuous process and not a 'once and for all' project

Question 288#

A 67-year-old man presents feeling 'generally unwell' and complaining of pain in his back and legs. His wife also reports that he has been slightly confused for the past two weeks.

Basic blood tests are ordered:

• Hb 12.1 g/dl
• Platelets 411 * 10⁹/l
• WBC 7.6 * 10⁹/l
• Na⁺ 143 mmol/l
• K⁺ 5.3 mmol/l
• Urea 15.7 mmol/l
• Creatinine 208 μmol/l
• Bilirubin 20 μmol/l
• ALP 110 u/l
• ALT 55 u/l
• γGT 67 u/l
• Albumin 31 g/l
• Total protein 84 g/l
• Calcium 3.10 mmol/l
• Phosphate 0.79 mmol/l

What is the most likely underlying diagnosis?

A. Multiple myeloma

Correct Answer A:

Hypercalcaemia, renal failure, high total protein = myeloma.

One of the stand out results is the high calcium level. This immediately narrows the differential diagnosis considerably. Remember the two most common causes of hypercalcaemia are malignancy and primary hyperparathyroidism. Neither of these alone would however explain the renal failure and high total protein, both common features of untreated myeloma. 

Myeloma: features:
Multiple myeloma is a neoplasm of the bone marrow plasma cells. The peak incidence is patients aged 60-70 years. 

Clinical features:

• Bone disease: bone pain, osteoporosis + pathological fractures (typically vertebral), osteolytic lesions
• Lethargy
• Infection
• Hypercalcaemia (see below)
• Renal failure
• Other features: amyloidosis e.g. Macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity

Diagnosis is based on:

• Monoclonal proteins in the serum and urine (Bence Jones proteins)
• Increased plasma cells in the bone marrow
• Bone lesions on the skeletal survey

Hypercalcaemia in myeloma:

• Due primarily to increased osteoclastic bone resorption caused by local cytokines released by the myeloma cells
• Other contributing factors include impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels

Question 289#

A 29-year-old man presents with a productive cough, fever and pleuritic chest pain. A chest x-ray shows lobar consolidation and a sputum culture grows Haemophilus influenzae. This is his fourth chest infection in the past seven months. Streptococcus pneumoniae has been grown from the sputum of the previous three episodes. Six weeks following the latest infection a full blood count, urea and electrolytes, CRP and chest x-ray are all reported as normal.

What is the most appropriate next investigation?

A. Serum immunoglobulins

Correct Answer A:

This patient has had repeated infections with encapsulated bacteria which should raise the suspicion of immunoglobulin deficiency. HIV would be suggested by infections associated with impaired cellular immunity.

Immunoglobulins:

The table below summarizes the characteristics of the 5 types of immunoglobulin found in the body:

Question 290#

Which one of the following genetic conditions is the most prevalent in a Caucasian population?

A. Wilson's disease

Correct Answer E:

Haemochromatosis is more common than cystic fibrosis:

Haemochromatosis is an autosomal recessive disorder with a carrier rate of 1 in 10 and is present in about 1 in 200-400 people. Cystic fibrosis (CF) has a carrier rate of 1 in 25 and is present in about 1 in 2,500 births. CF is often quoted as being the most common lethal inherited condition in Caucasians.

Haemochromatosis: features: 

Haemochromatosis is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation. It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6*. It is often asymptomatic in early disease and initial symptoms often non-specific e.g. lethargy and arthralgia.

Epidemiology:

• 1 in 10 people of European descent carry a mutation genes affecting iron metabolism, mainly HFE
• Prevalence in people of European descent = 1 in 200

Presenting features:

• Early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)
• 'Bronze' skin pigmentation
• Diabetes mellitus liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)
• Cardiac failure (2nd to dilated cardiomyopathy)
• Hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)
• Arthritis (especially of the hands)

Questions have previously been asked regarding which features are reversible with treatment:

*There are rare cases of families with classic features of genetic haemochromatosis but no mutation in the HFE gene

**Whilst elevated liver function tests and hepatomegaly may be reversible, cirrhosis is not