A Case of Alkaptonuria: Unexplained Arthropathy, Urine Discoloration, and the Importance of Metabolic Clues in Rare Diagnoses

Abstract

Introduction
Alkaptonuria is a rare autosomal recessive metabolic disorder caused by homogentisate 1,2-dioxygenase (HGD) deficiency, leading to the accumulation of homogentisic acid (HGA). This condition manifests through dark urine, progressive ochronosis (tissue pigmentation), early-onset arthritis, and may include cardiovascular complications.
This case highlights the importance of considering metabolic etiologies in early degenerative joint disease, particularly when accompanied by systemic signs like urine discoloration and scleral pigmentation. It adds to scientific literature by reaffirming that rare diseases can present even in under-resourced settings and require clinical vigilance for early diagnosis and intervention.

Patient Concerns and Key Clinical Findings
A young adult male presented with:
Urinary changes: Darkening of urine upon standing.
Ochronosis:
Bluish-black pigmentation of sclera
Pigmentation of ear cartilage and skin folds
Ochronotic arthropathy:
Progressive joint pain and stiffness
Affected areas: thoracolumbar and lumbosacral spine, large joints (knees, hips)
X-rays revealed: intervertebral disc calcification, joint space narrowing
Cardiovascular involvement:
Evidence of aortic valve calcification on echocardiography

Diagnosis
Clinical Clues:
Progressive early-onset arthropathy
Urine discoloration
Visible pigmentation (ochronosis)
Laboratory Findings:
Ferric chloride test: Black coloration
Benedict’s test: Green to black precipitate
Gas chromatography–mass spectrometry (GC-MS): Elevated homogentisic acid (HGA)
Genetic testing: Mutation in HGD gene confirmed diagnosis

Interventions
1. Symptomatic Management:
NSAIDs for joint pain and stiffness
Physiotherapy to preserve joint mobility
2. Dietary and Medical Support:
Low-protein diet to reduce phenylalanine and tyrosine intake (precursors of HGA)
Vitamin C supplementation to slow oxidative polymerization of HGA
3. Monitoring and Surveillance:
Serial imaging to monitor spinal and joint degeneration
Regular urinalysis for metabolic monitoring
4. Genetic Counseling:
Family screening and education about autosomal recessive inheritance
Carrier testing for first-degree relatives
5. Orthopedic Referral:
For early assessment and management of degenerative joint changes

Outcomes
At 3-month follow-up:
Joint symptoms moderately improved with NSAIDs and physiotherapy
Urine discoloration persisted
Patient reported better functional capacity in daily activities
Adherence to lifestyle and diet modifications was satisfactory

Conclusion and Key Takeaways
Think metabolic in unexplained early-onset arthritis—especially when accompanied by systemic clues.
Urine discoloration is a simple but underrecognized diagnostic sign of alkaptonuria.
Ochronosis, though delayed, is a diagnostic hallmark.
Early diagnosis and multidisciplinary care can improve quality of life and delay joint deterioration.
Rare diseases occur even in rural or peripheral health settings, emphasizing the need for awareness and basic metabolic workups in atypical arthropathy cases.