Case report 1

 4 month old baby girl

 Blackish discoloration of urine (2.5 mths)

 Non consanguineous marriage

 Normal growth and development

 Urine examination –
 Dark greenish black discoloration
 Homogentisic acid – 112 mg/dl

 No treatment

 Review at 6 months
 Case report 2
 43 year old woman

 Bluish discoloration of ears – 3 yrs

 Bluish-black staining of armpit - 6 mths

 Right lower back and bilateral knee pain

– 1 yr

 Daily estrogen, multivitamins, ibuprofen

 Sibling with similar affection

 Cardiac, ophthalmologic and dental examinations –
normal

 Echocardiogram – normal

 Orthopaedic – limited spinal range of motion

 X-rays  marked degenerative disc disease at T12-S1

 Anterior osteophytosis at T11-L2

 Urine exhibited darkening –
 Turned black immediately
on addition of 5 cm3 silver
nitrate and alkalinization
with 3 drops dilute
ammonia

 Punch biopsy –
 Degenerative change and
focal yellow-brown
pigmentation of cartilage

 Fishberg test – positive

 Gas chromatography and

mass spectrometry shows
large amounts of urinary
HGA
 What are the differential
diagnosis?
 Blue napkin syndrome (Tryptophan)

 Argyria

 Chrysiasis

 Drug induced pigmentation

 Exogenous ochronosis

 Haemchromatosis

 Naevus of ito
 How to confirm the
diagnosis?
 Detecting of HGA in urine – gas chromatography
mass spectrometry (1-8 gm/24 hr)

 X ray for IV calcification and narrowing

 Alkali test: addition of few drops of alkali such as
sodium hydroxide or potassium hydroxide darkens
the urine.
 Photographic paper test: a drop of urine over
photographic paper + few drops of NaOH = black
spot on the photographic paper.
 “Black” Benedict’s test: when urine is added to
Benedict’s reagent = a black coloured ring.
 Ferric chloride test: addition of ferric chloride to
urine = black colour.
What is the cause?
 Autosomal recessive

 Organic aciduria

 Deficiency of
homogentisic acid
oxidase (Chr 3; q21-23.6)

 Excessive homogentisic
acid in urine

 Accumulation of
homogentisic acid in
dermis and connective
tissue
 What is the management?
 Dietary restriction of phenylalanine and tyrosine

 Vitamin C

 Vitamin B12

 NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-
cyclohexanedione)

 Nitisinone
 Any other ways of
confirming diagnosis?
 Darkening of cerumen

 Pigmentation of cartilage and IV discs

 Pigmentation of connective tissues

 Arthritis

 Bluish pigmentation of sclera

 Pigmented renal and prostatic stones

 Prognosis?
 Slow and irreversible

 Life expectance is normal

 Arthropathy in 3rd-4th decade

 Calcification of heart valves

 Arteriosclerosis
Feature Age of occurrence
Darkening of urine, brownish First few days – first decade
stains
Dark brown or black cerumen First decade
Axillary pigmentation, brownish 8 – 10 years
punctiform coloration
Grayish-blue tinge of ear 20 years
cartilage
Discoloration of sclera, cornea, Adulthood
conjunctiva, tarsus, eyelid skin
Arthropathy 3rd – 4th decade
Renal and prostatic calculi 5th decade
 Tinnitus, hearing loss and erosion of cartilage

 Hoarseness and dysphagia

 Calcification of cardiac valve and valvular stenosis

 Other organs:
 Breast
 Lymph nodes
 Bone marrow
 Thyroid
 Teeth
 Other disorders in amino
acid metabolism
Disease Features Deficiency enzyme
Argininosuccinic Trichorrhexis nodosa Argininosuccinase
aciduria Rough skin
Aspartylglycosaminuria Thick skin Aspartylglycosamidase
Coarsening of facies
Sagging skin folds
Increased acne
Photosensitivity
Biotinidase deficiency Erythematous rash Biotinidase
Alopecia
Oral candidiases
Seborrheic dermatitis
Glossitis

Citrullinemia light, short hair Argininosuccinate

synthetase
Disease Features Deficiency enzyme
Hartnup disease Pellagra like lesions Neutral amino acid
Photosensitivity transport
Histidinemia Light colored hair and Histidase
eye
Holocarboxylase Seborrheic dermatitis Holocarboxylase
synthetase deficiency Alopecia synthetase

Homocystinuria Fine, sparse, friable Cystathionine beta-

hair synthetase
Thin skin
Livedo reticularis
Malar flush
Hydroxylkynureninuria Chronic stomatitis Kynureninase
Disease Features Deficiency enzyme
Hyperprolinemia Ichthyosis Proline oxidase
Iminodipeptiduria Chronic skin ulcers Prolidase
Isovaleric acidemia Odor of sweaty feet Isovaleryl-coenzyme
Alopecia A dehydrogenase
Methionine White hair Defective
malabsorption Dried celery or methionine
syndrome oasthouse odor transport
Edema
Xanthenurenic Urticaria Kynureninase
aciduria
 References
 Datta AK, Mandal S, Dasgupta A, Ghosh TK.
Alkaptonuria diagnosed in a 4-month-old baby girl: a
case report. The Cases journal 2008; 1:308-311.
 Turiansky GW, Levin SW. Bluish patched on the ears
and axillae with dark urine: ochronosis and
alkaptonuria. Int J Dermatol 2001; 40(5):333-335.
 Verma SB. Early detection of alkaptonuria. Indian J
Dermatol Venereol Leprol 2005;71:189-91.
 Ranjha KM, Aslam S, Mahmood T. Case Report
Alkaptonuria- a rare metabolic disorder
 Sanji RR, Reddy KE, Channegowda C. Alkaptonuria:
Otolaryngologic clues to diagnosis. Ind J Otology
2011; 17(1): 22-25