VISUAL VIGNETTE
Back Pain in a Middle-Aged Man: Alkaptonuria Ummais N. Khan, MD, Cornelia Wenokor, MD, and Eric L. Altschuler, MD, PhD From the Rutgers New Jersey Medical School (UNK, CW), Department of Physical Medicine and Rehabilitation (UNK), and Department of Radiology (CW), The State University of New Jersey, Newark; and Department of Physical Medicine and Rehabilitation, Temple University School of Medicine, Philadelphia, Pennsylvania (ELA). Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. 0894-9115/15/9405-e42 American Journal of Physical Medicine & Rehabilitation Copyright * 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/PHM.0000000000000253
A
43-yr-old man with a medical history notable for cross fused renal ectopia presented for initial evaluation of worsening lower back pain and bilateral knee pain for 4 yrs. Physical examination was remarkable only for a thoracic kyphosis. Further history revealed that the patient had normal functional status and was working full time. He was using Tylenol for adequate pain relief. Lumbar spine x-ray, bilateral knee x-rays, and a complete course of physical therapy were ordered on this initial visit. On a follow-up visit, the patient reported the physical therapy course to be unhelpful. Lumbar spine x-rays (Fig. 1) were found to be consistent with alkaptonuria (AKU), demonstrating severe, diffuse disk degeneration and disk calcifications throughout the visualized dorsal spine. Bilateral knee x-rays did not show any abnormalities. Physical examination during this visit revealed darkly pigmented sclera and bluetinged discoloration of the concha of both ears. The patient’s urine was dark (teak color). A presumptive diagnosis of AKU was made, and the patient was referred for further diseasespecific testing, cardiac evaluation, and orthopedic spine surgery evaluation. Homogentisic acid was found to be high, confirming the clinical and radiographic diagnosis. Cardiac workup revealed normal echocardiogram results. Orthopedic spine surgery evaluation was ordered and is still pending. AKU is a classic autosomal recessive disorder, indeed one of the first, described by Garrod in 1902.1 AKU is caused by a defect in the enzyme homogentisate 1,2-dioxygenase, which participates in the degradation of tyrosine leading to excessive homogentisic acid.2 However, management with low-tyrosine (low-protein) diet has been found to be difficult to comply with, and no long-term efficacy studies have been performed. Other treatments such as large doses of ascorbic
All correspondence and requests for reprints should be addressed to: Eric L. Altschuler, MD, PhD, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140.
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FIGURE 1 Lateral radiograph of the lumbar spine demonstrates diffuse disk degeneration throughout the entire spine with severe disk space narrowing. There are central disk calcifications at T11YT12 through L2YL3 (upper arrow), involving the nucleus pulposus. Osteophytic lipping is seen throughout the spine but is relatively mild. A vacuum phenomenon (lower arrow) is seen at L2YL3 through L5YS1.
acid were thought to decrease formation of homogentisic acid by blocking benzoquinone acetic acid. However, studies revealed no effect on homogentisic acid excretion or clinical effectiveness. Currently, treatment with nitisinone is under trial. It inhibits 4-hydroxy-phenyl-pyruvate-dioxygenase and therefore decreases formation of homogentisic acid. Further management of AKU patients should also include cardiology referral because cardiac arrhythmias and valvular heart disease are commonly found in this patient population.2 All low back pain is not caused by age-appropriate degenerative joint disease. Indeed, low back pain may be the most common initial presentation of AKU to healthcare professionals. Physiatrists should consider AKU as a possible differential diagnosis for patients presenting with disproportionate disk degeneration for their biologic age resulting in back pain as illustrated above. REFERENCES 1. Garrod AE: The incidence of alkaptonuria: A study in chemical individuality. Lancet 1902;2:1616Y20 2. Ranganath LR, Jarvis JC, Gallagher JA: Recent advances in management of alkaptonuria (invited review; best practice article). J Clin Pathol 2013;66:367Y73
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 5, May 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Back Pain in a Middle-Aged Man: Alkaptonuria Ummais N. Khan, MD, Cornelia Wenokor, MD, and Eric L. Altschuler, MD, PhD From the Rutgers New Jersey Medical School (UNK, CW), Department of Physical Medicine and Rehabilitation (UNK), and Department of Radiology (CW), The State University of New Jersey, Newark; and Department of Physical Medicine and Rehabilitation, Temple University School of Medicine, Philadelphia, Pennsylvania (ELA). Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. 0894-9115/15/9405-e42 American Journal of Physical Medicine & Rehabilitation Copyright * 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/PHM.0000000000000253
A
43-yr-old man with a medical history notable for cross fused renal ectopia presented for initial evaluation of worsening lower back pain and bilateral knee pain for 4 yrs. Physical examination was remarkable only for a thoracic kyphosis. Further history revealed that the patient had normal functional status and was working full time. He was using Tylenol for adequate pain relief. Lumbar spine x-ray, bilateral knee x-rays, and a complete course of physical therapy were ordered on this initial visit. On a follow-up visit, the patient reported the physical therapy course to be unhelpful. Lumbar spine x-rays (Fig. 1) were found to be consistent with alkaptonuria (AKU), demonstrating severe, diffuse disk degeneration and disk calcifications throughout the visualized dorsal spine. Bilateral knee x-rays did not show any abnormalities. Physical examination during this visit revealed darkly pigmented sclera and bluetinged discoloration of the concha of both ears. The patient’s urine was dark (teak color). A presumptive diagnosis of AKU was made, and the patient was referred for further diseasespecific testing, cardiac evaluation, and orthopedic spine surgery evaluation. Homogentisic acid was found to be high, confirming the clinical and radiographic diagnosis. Cardiac workup revealed normal echocardiogram results. Orthopedic spine surgery evaluation was ordered and is still pending. AKU is a classic autosomal recessive disorder, indeed one of the first, described by Garrod in 1902.1 AKU is caused by a defect in the enzyme homogentisate 1,2-dioxygenase, which participates in the degradation of tyrosine leading to excessive homogentisic acid.2 However, management with low-tyrosine (low-protein) diet has been found to be difficult to comply with, and no long-term efficacy studies have been performed. Other treatments such as large doses of ascorbic
All correspondence and requests for reprints should be addressed to: Eric L. Altschuler, MD, PhD, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140.
e42
FIGURE 1 Lateral radiograph of the lumbar spine demonstrates diffuse disk degeneration throughout the entire spine with severe disk space narrowing. There are central disk calcifications at T11YT12 through L2YL3 (upper arrow), involving the nucleus pulposus. Osteophytic lipping is seen throughout the spine but is relatively mild. A vacuum phenomenon (lower arrow) is seen at L2YL3 through L5YS1.
acid were thought to decrease formation of homogentisic acid by blocking benzoquinone acetic acid. However, studies revealed no effect on homogentisic acid excretion or clinical effectiveness. Currently, treatment with nitisinone is under trial. It inhibits 4-hydroxy-phenyl-pyruvate-dioxygenase and therefore decreases formation of homogentisic acid. Further management of AKU patients should also include cardiology referral because cardiac arrhythmias and valvular heart disease are commonly found in this patient population.2 All low back pain is not caused by age-appropriate degenerative joint disease. Indeed, low back pain may be the most common initial presentation of AKU to healthcare professionals. Physiatrists should consider AKU as a possible differential diagnosis for patients presenting with disproportionate disk degeneration for their biologic age resulting in back pain as illustrated above. REFERENCES 1. Garrod AE: The incidence of alkaptonuria: A study in chemical individuality. Lancet 1902;2:1616Y20 2. Ranganath LR, Jarvis JC, Gallagher JA: Recent advances in management of alkaptonuria (invited review; best practice article). J Clin Pathol 2013;66:367Y73
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 5, May 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
