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| CASE REPORT |
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| Year : 2016 | Volume
: 3
| Issue : 1 | Page : 49-51 |
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Palmar pigmentation: An unusual presentation of alkaptonuria
H. V. S. Naveen Kumar, C Natraj Hiremath, N Bhuvanaa Sree, A Vijaya Mohan Rao
Department of Dermatology, Venereology and Leprosy, Narayana Medical College, Nellore, Andhra Pradesh, India
| Date of Web Publication | 17-Jun-2016 |
Correspondence Address:
Dr. H. V. S. Naveen Kumar
Flat No: 201, H. No: 1-1-524, R. R. Arcade, Gandhinagar, Hyderabad, Telangana - 500 080
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2349-5847.184245
Alkaptonuria (AKU) is a rare inherited autosomal recessive metabolic disorder, caused by the deficiency of homogentisic acid oxidase enzyme. Herein, we are reporting a case of AKU with bilaterally symmetrical palmar pigmentation and skeletal involvement. Histopathological examination revealed ochre colored pigment in the dermis whereas roentgenogram of the lumbar spine showed typical calcification of the intervertebral discs. Keywords: Alkaptonuria, disc calcification, homogentisic acid, palmar pigmentation
How to cite this article:
Kumar HN, Hiremath C N, Sree N B, Rao A V. Palmar pigmentation: An unusual presentation of alkaptonuria. Pigment Int 2016;3:49-51 |
| Introduction | |  |
Alkaptonuria (AKU) is a rare inherited disorder of amino acid metabolism that occurs due to deficiency of the enzyme homogentisic acid (HGA) oxidase which catalyzes the conversion of HGA to maleylacetoacetic acid in the catabolism of tyrosine. It is characterized by the triad of homogentisic aciduria, ochronosis, and precocious degenerative arthropathy. It is one of the first conditions in the charter of group of inborn errors of metabolism proposed to have Mendelian recessive inheritance. The incidence of AKU is 1 in 250,000 to 1 in 1,000,000 live births.[1] This case has been brought to light as only a few cases of AKU were reported; more so with palmar involvement. Our case presented with bilaterally symmetrical bluish palmar pigmentation and that posed a challenge to unravel the diagnosis.
| Case Report | | |
A 43-year-old male came to outpatient department with bluish discoloration over palms for 1 year. He also had complaints of back pain for 6 months, stiffness of knee joints for 2 months. He was aware of brown to black discoloration of urine for the past 2 years. No similar lesion was known to be present in his family. He was a product of a second degree consanguineous marriage. Dermatological examination revealed bilaterally symmetrical nontender, bluish papules with pitting, and crateriform plaques on palms [Figure 1]. Few hyperpigmented plaques were noted on the dorsum of hands and feet. Nail beds of both hands and feet showed bluish-gray discoloration. Black pigmentation was noticed at the fossa triangularis of both ears. Osler's sign was noted over the sclera of both eyes [Figure 2] and [Figure 3]. Percussion of lumbosacral spine exhibited moderate tenderness. There was no laxity of the collateral or cruciate ligaments. | Figure 1: Pigmentation along the margins of the palms and tips of the fingers
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His blood counts, liver, and kidney function tests were within normal limits. Urine turned progressively darker with time on exposure to air [Figure 4]. Ferric chloride test was positive. The radiographs of lumbosacral spine showed multi-level intervertebral disc calcification while that of the knee joints showed the presence of osteophytes and early osteoporotic changes [Figure 5]. | Figure 4: X-ray of lumbo-sacral spine showing intervertebral disc calcification and sacralization of L5 and knee joint showing osteophytes with osteoporosis
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Skin biopsy from the crateriform plaques on the palms showed a hyperkeratotic epidermis with ochre colored (yellowish) pigmentary deposits over broken collagen bundles (banana bodies) [Figure 6]. | Figure 6: Photomicrograph showing thickened collagen bundles with deposition of brownish pigmented material in the dermis (H and E, ×40). Inset: Banana bodies in the dermis (H and E, ×100)
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He was prescribed oral ascorbic acid 1 g/day and was counseled to avoid foods high in phenylalanine and tyrosine such as egg, seafoods, meat, dairy products, soy products, beans, and sesame seeds. The patient was informed about the nature of the disease and asked to come for regular follow-ups.
| Discussion | | |
Alkaptonuria (AKU) was first described in 1902 by Garrod and Bateson.[2] It is a rare metabolic disorder of phenylalanine catabolism and is inherited as an autosomal recessive trait. It is caused by a deficiency in homogentisic acid oxidase (HGO) which converts HGA to maleylacetoacetate in the phenylalanine/tyrosine catabolic pathway in the liver, kidney, prostate, small intestine and colon. The accumulation of HGA and its oxidized product benzoquinone in the body leads to the characteristic symptoms (black urine, ochronosis, and arthritis) of the disease. Patients may be homozygous or compound heterozygous for loss-of-function mutations in the HGO gene. Enzyme deficiency was identified by La Du in 1958.[3] Our case was a product of the second degree consanguineous marriage.
One of the first symptoms of AKU is darkening of urine on standing that was evident in this case. The patients are usually asymptomatic until the third decade. Scleral pigmentation (Osler's sign) usually starts around the third decade. Patient presents in the middle or late life with back pain due to spinal ochronotic spondylosis and the characteristic densely calcified intervertebral discs with relatively few other symptoms of degenerative arthritis. In contrast to rheumatoid arthritis, the small joints of the hands and feet are usually not affected. Our patient had positive Osler's sign, disc calcifications, and osteophytes.
Cutaneous findings include pigmentation of skin which starts around the fourth decade. One of the first sites to be affected is the ear cartilage involving concha, antihelix, and tragus in that order (ochronosis).[4] There are few case reports where palmoplantar pigmentation was the presenting complaint.[5],[6] The discoloration tends to be most pronounced on sun-exposed sites, cartilage of the ears and nose, areas of high eccrine sweat gland density, such as axillae, palms, soles, and genitalia.[7] The bluish discoloration of mucosae and tendons, especially dorsum of hands, nail bed, and crown half of the teeth may be seen. Our case presented with bilaterally symmetric bluish palmar pigmentation with black pigmentation of ears. The differential diagnoses for the palmar pigmentation are plaque-type blue cell nevus and acquired dermal melanocytosis. Histopathology reveals ochronotic pigment deposits in contrast to the presence of melanocytes in the dermis in the other conditions.
An increased amount of HGA in the urine estimated by gas chromatography–mass spectrometry confirms the diagnosis of the disorder.[8],[9] Screening for mutations is done after extracting the genomic DNA from whole blood and subjecting it to polymerase chain reaction.[10] These investigations were not done in our patient due to limited resources.
There is no effective treatment for AKU. Some studies have reported success with dietary protein restriction and using Vitamin C and nitisinone [11] therapies. Other agents such as Vitamin B12, cortisone and phenylbutazone have been tried. Supportive therapy like NSAIDs and physical therapy are used for arthropathy. Cases of AKU keep resurfacing from time to time in medical literature since 1902, but more than 100 years later, there is still no cure and often overlooked.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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| 9. | Seegmiller JE, Zannoni VG, Laster L, La Du BN. An enzymatic spectrophotometric method for the determination of homogentisic acid in plasma and urine. J Biol Chem 1961;236:774-7. [ PUBMED] |
| 10. | Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, et al. Natural history of alkaptonuria. N Engl J Med 2002;347:2111-21. |
| 11. | Suwannarat P, O'Brien K, Perry MB, Sebring N, Bernardini I, Kaiser-Kupfer MI, et al. Use of nitisinone in patients with alkaptonuria. Metabolism 2005;54:719-28. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
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