Identification of HGD mutations in an alkaptonuria patient: using the Internet to seek rare diseases

Alkaptonuria (AKU, OMIM: 203500) is a rare autosomal recessive disorder of tyrosine metabolism due to a defect of enzyme activity, homogentisate 1,2-dioxygenase (HGD). The patients with AKU initially presented with dark urine discoloration, and ochronosis and arthritis develop after third decades of life. With advances of Internet resources, web-based health seekers for rare disease are increasing. Here, we report the case of an 18-year-old boy with AKU who visited our center due to dark black urine based on self-diagnosis via web searching of this rare condition. Compound heterozygous mutations in HGD gene, IVS5+3A>C and IVS12+6T>C were identified and both of mutations were detected in his parents. Our case illustrates the utility of publicly available Internet resources for diagnosis of rare disease.

Cervical Spondylotic Myelopathy due to the Ochronotic Arthropathy of the Cervical Spine

Ochronosis is a musculoskeletal manifestation of alkaptonuria, a rare hereditary metabolic disorder occurs due to the absence of homogentisic acid oxidase and leading to various systemic abnormalities related to deposition of homogentisic acid pigmentation (ochronotic pigmentation). The present case reports the clinical features, radiographic findings, treatments and results of a cervical spondylotic myelopathy woman patient due to the ochronotic arthropathy of the cervical spine. The patient aged 62 years was presented with gait disturbance and hand clumsiness. Physical examination, X-rays, computed tomography and lab results of the urine sample confirmed the presence of ochronosis with the involvement of the cervical spine. The patient underwent a modified cervical laminoplasty due to multi-segment spinal cord compression. The postoperative follow-up showed a good functional outcome with patient satisfaction. The present study concludes the conditions and important diagnostic and surgical aspects of a patient. It is necessary to identify the condition clinically and if cord compression is observed, appropriate surgical interventions needs to be instituted.

Early diagnosis of co-existent ß-thalassemia and alkaptonuria.

Since the aggregate incidence of inborn errors of metabolism is relatively high, a high degree of suspicion is essential to correctly diagnose an inborn error of amino acid metabolism. We report a case of alkaptonuria an autosomal recessive disorder that occurs due to deficiency of homogentisic acid oxidasein a β-thalassemia infant presenting with reddish discoloration of nappies and clothes, breath holding spells, and microcytic hypochromic anemia. Born to consanguineous cousins, to our knowledge, the combination of β-thalassemia and alkaptonuria, which we have described in this baby, has not been reported earlier.

Alkaptonuria and intramedullary calcification.

Alkaptonuria is a rare disorder of metabolism caused by deficiency of homogentisic acid oxidase enzyme and characterized by triad of homogentisic aciduria (dark urine), relentlessly progressive arthritis and ochronosis. We have documented a case with typical features of alkaptonuria along with intramedullary calcification which has not been reported in the literature before.

A case of alkaptonuria: the first case in Korea / 소아과

Alkaptonuria is a rare metabolic disease in which homogentisic acid cannot be metabolized due to a lack of the enzyme homogentisic acid oxidase. The disease often manifests itself in childhood by darkening of the urine upon standing. The disease leads to such serious consequences as ochronosis of cartilage and connective tissues with arthritis. It is expected that treatment with ascorbic acid and a dietary restriction of protein may decrease the late and serious consequences by diminishing the serum concentration of the metabolite benzoquinone acetic acid. A thirteen month-old girl was recently diagnosed with alkaptonuria by urine organic acid analysis. She excreted pinkish urine on a diaper and as time went by the urine color changed to a light brown. In laboratory findings, urine examination and culture results were normal. But urine organic acid analysis detected abnormal findings a prominent and massive elevation of homogentisic acid. The other physical findings were normal. This is the first case diagnosed in Korea.

Early detection of alkaptonuria.

Alkaptonuria is a rare disorder of metabolism characterized by deficiency of homogentisic acid oxidase. This leads to the characteristic features like darkening of urine, ochronosis and arthropathy. Darkening of urine is one of the first symptoms noticed by the parents of the child suffering from this disorder. Ochronosis is seen in various organs like eyes, skin, tendons and joints. A case of 10 year old boy is reported who was brought to this clinic with the presenting complaint of bluish discoloration of sclerae. This discoloration led to eliciting positive history of dark urine off and on. Further investigations confirmed alkaptonuria.