Male

64 years old
Back pain
Generally unwell, tired
Weight loss (7kg in 6 months)

Na 145 mmol/L (135-145)
K 5.2 mmol/L (3.5-5.0)
Urea 20.2 mmol/L (2.5-7.5)
Creatinine 287 mol/L (60-120)
Total protein 98 g/L (60-80)
Albumin 34 g/L (35-50)
Corrected calcium 2.7 mmol/L (2.1-2.6)

Hb 78 g/L (130-180)
ESR 56 mm/hr (<7)
Blood film Normocytic, normochromic anaemia
Iron 18 mol/L (11-32)
TIBC 45 umol/L (45-70)
Iron saturation 40% (16-55)
IgG 45 g/L (8-17)
IgA <0.3 g/L (0.9-4.5)
IgM <0.2 g/L (0.6-2.7)


N
IgG IgA IgM
IgG IgA IgM
Further investigations

Bone marrow - increased numbers/atypical
plasma cells
X-ray - skull, chest. Osteolytic lesions

Monoclonal gammopathies

Monoclonal gammopathies of undetermined significance (62%)
Multiple myeloma (15%)
Amyloidosis (10%)
Waldenstroms macroglobulinaemia (3%)
Smouldering multiple myeloma (3-4%)
Lymphoproliferative disease (2.5%)
Solitary or extramedullary plasmacytoma (1.5%)
Other causes (2.5%)



Presentation of myeloma

Bone pain (back or chest) 60%
Weakness, fatigue (anaemia >60%)
Acute infections
Renal failure creatinine >175 mol/L in 20%
Hypercalcaemia 15%
Serum paraprotein 80% IgG 50%
IgA 20%
BJP 20%
IgD 2%
Biclonal 1%

Urine paraprotein 75%
Serum or urine paraprotein 98%, 2% non-secretory
Most have >10% plasma cells in bone marrow




Male
58 years old
Back pain
Na, K, urea, creatinine normal
Calcium, phosphate normal
Haematology normal
Total protein 79 g/L (60-80)
Albumin 37 g/L (35-50)

IgG 16 g/L (8-17)
IgA 2.8 g/L (0.9-4.5)
IgM 1.0 g/L (0.6-2.7)


IgG IgA IgM

Urine protein 0.04 g/24h <0.1
Urine protein electrophoresis No protein bands, no BJP

Serum paraprotein concentration = 3 g/L
No significant increase in next 3 years

Female
28 year old
Routine medical

ALT 135 U/L (<50)
ALP 129 U/L (<130)
Bilirubin 18 mol/L (<20)

ALT persistently raised in next 6 months

Viral screen negative
Requests:
AFP
1-antitrypsin
Ceruloplasmin
Iron / Iron binding capacity
AFP <5 KU/L (<10)
1-antitrypsin 0.2 g/L (1.1-2.1)
Ceruloplasmin 0.3 g/L (0.15-0.6)
Iron 15 mol/L (11-32)
Iron binding capacity 40 umol/L (45-70)
Iron saturation 38% (16-55)

1-antitrypsin phenotype PI ZZ

Family history:

Paternal uncle age 40 yrs has severe obstructive pulmonary
disease

Daughter, age 3, had neonatal hepatitis
Male
42 yrs old
Smoker 26 yrs
Emphysema on chest X-ray
Family history of COPD

1- antitrypsin = 0.6 g/L (1.1-2.1)

1- antitrypsin phenotype PI SZ



Female
32 yrs old
Referral to dermatologist with erosive skin lesions
Father (smoker) died of emphysema age 52

1- antitrypsin = 0.3 g/L (1.1-2.1)

1- antitrypsin phenotype PI ZZ


Female
23 yr old
Found collapsed, semi-conscious

Results 24 hours later

Na 135 mmol/L (135-145)
K 6.0 mmol/L (3.5-5.0)
Urea 18.0 mmol/L (2.5-7.5)
Creatinine 350 mol/L (60-120)
Corrected calcium 1.84 mmol/L (2.1-2.6)
Phosphate 1.5 mmol/L (0.8-1.6)
Bilirubin 10 mol/L (<20)
Alkaline phosphatase 105 (<130)
ALT 583 (<50)





Random urine blood +++
pigmented dark red/brown
CK 80100 U/L (<170)
Urine myoglobin 650000 g/L (<15)
Day Urine Mb CK creat Ca

1 650000 80170 350 1.65
3 12000 48000 500 1.86
4 7500 22385 692 1.84
6 620 4816 814 2.13
8 347 1479 811 2.34
10 40 581 856 2.54
11 25 369 837 2.53
Causes of rhadbomyolysis
Trauma
Ischaemia
Surgery
Exertion/stress
Exercise, seizures, heat
Metabolic
alcohol, malignant hyperthermia, genetic eg,
myophosphorylase deficiency, PFK deficiency, carnitine
palmitoyl transferase deficiency, electrolyte depletion eg. K, P
Toxic
drugs of abuse, venom, other toxins, prescribed drugs eg.
Statins
Myositis, idiopathic and familial myopathies
Infection



Male MW

Age 24 yrs

Presented 1996 Rochdale

12 month history of elevated ALT (85-145 U/L)
No jaundice
No alcohol, drugs
Viral screen negative

AFP 4 KU/L (<10)
1-antitrypsin 1.4 g/L (1.1-2.1)
Ceruloplasmin <0.06 g/L (0.15-0.6)
Iron 15 mol/L (11-32)
Iron binding capacity 46 umol/L (45-70)
Iron saturation 33% (16-55)
Slit lamp examination Kayser Fleischer rings

Serum copper 1.3 mol/L (13-24)

Urine copper 4.3 mol/24h (<1)



Given trientine 900 mg bd


Referred to Neurology Hope 2001


Irreversible brain damage

Severe disabilities

Wheelchair bound

Anarthric

Dysphagia and drooling

Spastic contractures of both limbs

Communicates via electronic keyboard

U Cu Se Cu Cer
11.3.96 7.4 1.4 <0.06
15.4.96 16.4
7.6.96 1.0
1.8.96 8.5
28.8.96 1.6
4.9.01 1.7 2.2 <0.06
26.1.03 3.1 0.3 <0.06
30.4.03 4.6 1.5 <0.06
24.3.04 2.4 <0.06
1.4.04 1.7
13.10.04 3.0
2.3.05 0.9 0.5
31.8.05 0.4 <0.06
10.9.05 2.3


Female S.B
20 yrs
Presented 1997
Sister of MW

se Cu Cer UCu
Jan 1997 1.3 <0.06 4.3

Sept 2001 2.4 <0.06 6.3

Jan 2003 0.9 <0.06 1.4

March 2005 0.6



Diagnosis of Wilsons disease

Unexplained liver, neurological disease, family history of confirmed or
suspected WD

Serum Cu, Cer
Slit lamp examination
Liver function tests
Urinary Cu

KF rings + low Cu + low cer = WD
No KF rings + low Cu + low cer check LFTs, urine Cu
No KF rings + normal Cu + normal cer probably not WD
Specialist investigations (difficult cases)

Gene tracking family members
Liver biopsy histology and Cu content (high values
diagnostic, low values do not exclude WD)
65
Cu incorporation can be diagnostic
Genetic studies Mutation detection