ALKAPTONURIA,TOTAL KNEE REPLACEMENT,OCHRONOSIS

1. Dr GOWTHAM K R
HOSMAT HOSPITAL

2.  59 yr old , female
 Pain in the left knee since 15 yr
 Right knee total knee replacement was
done 12yrs before
 History of low back pain since many
years

5. Posted for surgery on 12/12/17
 Anaesthetists were struggling to give spinal
anaesthesia……
Patient said-I have severe back pain
People say, I walk different
????Possibility of Ankylosing spondylitis

13. OCHRONOSIS: is a syndrome caused by the accumulation
of homogentisic acid in connective tissues
It was first described by Rudolf Virchow in 1865.
Two types of : Endogenous and Exogenous.
Endogenous - is an Autosomal recessive disease
 Exogenous - is an avoidable dermatitis, caused by the topical
application of compounds such as hydroquinone or phenols

14. ALKAPTONURIA
(Black urine disease, black bone disease)
Rare- inherited genetic disorder- body cannot process the amino
acids phenylalanine and tyrosine
 proMutation in the HGD gene for the enzyme
homogentisate 1,2-dioxygenase
Autosomal recessive
 HOMOGENTISIC ACID- accumulate in the blood and tissues
Homogentisic acid and its oxidized form alkapton are excreted in
the urine, giving it an unusually dark color

16.  Symptoms - >30 years
 Dark discoloration - birth.
one in 250,000 people
More common in Slovakia and Dominican Republic
Alkaptonuria does not appear to affect life expectancy
The main impact is on quality of life; many people with
alkaptonuria have disabling symptoms such as pain, poor sleep and
breathing symptoms.

17. Cartilage:
Mainly affects the cartilage and does not affect the subchondral bone
 Darkening and hardening of ear and Nasal cartilage
Voice can be affected -Stiffening of the ribs- decreased lung function-
Intravertebral cartilage is also more prone to herniation & calcification
Heart valves: Stenosis can results from the increased rigidity of the
connective tissue as well as chronic inflammation.
Connective tissue: Hardening of tendons and ligaments can predispose
them to rupture- Arthropathy is common due to chronic inflammation
and microruptures.
After the age of thirty people begin to develop pain in the weight-bearing
joints of the spine, hips and knees.

18. The pain can be severe to the point that interferes with activities of
daily living and may affect ability to work. Joint replacement surgery
is often necessary at a relatively young age.
Skin: The pigment is deposited throughout the skin -This usually
occurs in areas where connective tissue is thick- joints, tympanic
membrane or close to the surface of the skin thenar and hypothenar
eminences.
Eye: Darkening around the palpebral fissure-Cornea can become
hyperpigmented if exposed to phenol vapors.
Other: Propensity to developing kidney stones, gallstones and stones
in the prostate and salivary glands.

20. DIAGNOSIS:
Mainly clinical
Confirmed by collecting urine for 24 hrs and determining the amount
of homogentisic acid by means of chromatography.
There is no validated assay of HGA in blood.
The severity of the symptoms and response to treatment can be
quantified through -AKU Severity Score Index.
(Assigns scores to the presence of particular symptoms and features,
such as the presence of eye and skin pigmentation, joint pain, heart
problems and organ stones)

21. TREATMENT:
Commonly recommended treatments include large doses
of ascorbic acid (vitamin C)
Dietary restriction of amino acids phenylalanine and tyrosine.
However, vitamin C treatment has not shown to be effective, and
protein restriction (which can be difficult to adhere to) has not shown
to be effective in clinical studies.
There is no definitive cure for the disease but Nitisinone, an
inhibitor of 4-hydroxyphenyl pyruvate dioxegenase has been shown
to decrease urinary excretion of homogentisic acid .
Nitisinone - 95% reduction in plasma and urinary HGA.

22.  The main drawback is accumulation of tyrosine, the long-term
risks of which are unknown
 There is a particular concern about damage to the cornea of the
eye.
Long-term use would require frequent monitoring for
complications.
The effectiveness of Nitisinone in treating ochronosis is
unknown.
Osteo arthritis- The average age at requiring joint replacement
surgery is 50–55 years.

23. KEY POINTS:
A high suspicion and good history taking is required for preoperative
diagnosis.
• Consider preoperative cardiac clearance because of possibility of
calcified cardiac valve disease.
• Be careful while retracting the patella, quadriceps rupture has been
reported .
• Be careful while making cuts and consider use of cement because of
softness of bones.
• Excess blood loss intra and postoperatively may occur. Consider
tranexamic acid to decrease blood loss
 Be careful about possibility of infection and soft tissue healing

24. Current controversies and future considerations
Possible genetic interventions or the use of Nitisinone for
treatment of this disorder considered
Blood management
Use of bone cement
Further research in these areas may be helpful.

25. References:
1. Selvi E., Manganelli S., Mannoni A. Chronic ochronotic arthritis:
clinical, arthroscopic, and pathologic findings. J Rheumatol. 2000
Sep;27(9):2272. [PubMed]
2. Demir S. Alkaptonuric ochronosis: a case with multiple joint
replacement arthroplasties. Clin
Rheumatol. 2003;22:437. [PubMed]
3. Nas K., Gür A., Akdeniz S. Ochronosis: a case of severe
ochronotic arthropathy. Clin Rheumatol. 2002
May;21(2):170. [PubMed]
4. Wauthy P., Seghers V., Mathonet P., Deuvaert F.E. Cardiac
ochronosis: not so benign. Eur J Cardiothorac Surg. 2009
Apr;35(4):732. Epub 2009 Feb 10. [PubMed]

26. 5. Farzannia A., Shokouhi G., Hadidchi S. Alkaptonuria and lumbar
disc herniation. Report of three cases. J Neurosurg. 2003 Jan;98(1
Suppl.):87. [PubMed]
6. Aynaci O., Onder C., Turhan A.U. Bilateral hip arthroplasty for
ochronotic arthropathy. Clin Rheumatol. 2000;19:150. [PubMed]
7. Spencer J.M., Gibbons C.L., Sharp R.J. Arthroplasty for
ochronotic arthritis: no failure of 11 replacements in 3 patients
followed 6-12 years. Acta Orthop Scand. 2004
Jun;75(3):355. [PubMed]
8. Carrier D.A., Harris C.M. Bilateral hip and bilateral knee
arthroplasties in a patient with ochronotic arthropathy. Orthop
Rev. 1990;19:1005. [PubMed]

27. Thank you…..