Ochronosis and alkaptonuria is a related condition that results from the inability to metabolise amino acids and hence the buildup of homogentisic acid. Ochronosis is the state which is manifested in bluish or black coloration of connective tissues because of accumulation of homogentisic acid. Alkaptonuria is a very rare inherited metabolic disease which is an autosomal recessive trait that is due to the deficiency of the enzyme homogentisate 1,2-dioxygenase. This enzyme played an important role in the breakdown of Tyrosine and Phenylalanine amino acids. This deficiency results in deposition of homogentisic acid that is later excreted through urine.
Epidemiology
Alkaptonuria is a rare genetic disorder that is inherited through autosomal recessive mode, with an incidence of 1 in a million. The disease is spread all over the world with the highest incidence rate recorded in Slovakia and Dominican Republic impacting about one in 19,000 population. Though alkaptonuria can occur in anyone, irrespective of the color of their skin, exogenous ochronosis which is brought about using cosmetic products that lighten the skin such as hydroquinine is more prevalent in the African and Afro-Caribbean zones.
The condition is common in male and female in equal proportion. It is congenital, and it is normally diagnosed when the diapers are discolored blue. However up to 25% of those with alkaptonuria do not show the dark urine staining and hence are usually diagnosed later in life.
Anatomy
Pathophysiology
Alkaptonuria is characterized by decolorization of connective tissues following in addition to the yellowish or ochre hue termed by Virchow as Ochronosis. Alkaptonuria is a very rare metabolic disease which is an autosomal recessive trait caused by deficiency of homogentisic acid oxidase an enzyme which is responsible for phenylalanine and tyrosine catabolism. This results in the build-up of homogentisic acid in cartilage which gives a bluish-black colour to the affected area. During the development of this process, tensile forces lead to the accumulation of stress on connective tissues causing inflammation, degenerative process and osteoarthritis.
Etiology
Ochronosis is a result of oxidation of the accumulated homogentisic acid in connective tissues because of alkaptonuria. This deposition occurs out of lack of homogentisic acid oxidase in genetic process and it causes tissues a bluish-black color. Alkaptonuria is an autosomal recessive disease, which results due to deficiency of homogentisic acid oxidase. It also affects the sheer breakdown of homogentisic acid, and this leads to accumulation of homogentisic acid and deposition in tissues.
Genetics
Prognostic Factors
Life expectancy in alkaptonuria patients is normal but there may be severe arthritic complications, cardiovascular diseases, and change of color of the skin known as ochronosis. This condition can further exacerbate the mentioned complications in chronic kidney disease. The condition is primarily due to the deficiency of homogentisic acid (HGA) oxidase and is characterized by high levels of HGA. This results into blue-black pigmentation of the skin, particularly in the connective tissues and leads to darkening of urine. Accumulation of HGA destroys collagen which triggers arthritis and joint breakdown, particularly in large joints. Further, changes can occur at the structural level of blood vessels and these changes can trigger cardiovascular problems. HGA becomes dark on exposure to air and in presence of alkalis but it may not be very dark colored in acidic urine.
Clinical History
Age Group
Alkaptonuria:
Infancy: It is a congenital condition, but manifestation of the different symptoms may not be observed right from birth.
30s-40s: This is the time that patients start complaining of pains in the joints as well as dark urine.
50s-60s: Consequently, severe complications those include arthritis and ochronosis may tend to aggravate in this age range.
Ochronosis: Typically Seen in Adulthood: Connective tissue and cartilage are also involved bluish-black pigmentation that forms middle age or later and in patients with established alkaptonuria.
Physical Examination
Ochronosis:
Skin: Bluish-black discoloration, especially in areas exposed to sunlight.
Cartilage: Bluish-black pigmentation in cartilage (e.g., nose, ears).
Joints: Signs of arthritis, particularly in larger joints; possible early calcification and disc narrowing.
Alkaptonuria:
Urine: Dark-colored urine that turns black upon standing.
Joints: Joint pain, swelling, and deformity, with early calcification and degeneration, especially in larger joints.
Skin: Possible bluish-black pigmentation in connective tissues (similar to ochronosis).
Age group
Associated comorbidity
Alkaptonuria:
Arthritis: Ochronotic arthropathy tends to involve the larger weight-bearing joints and the changes are characterized by early calcification and degenerative process.
Cardiovascular Disease: This leads to changes in vessel walls also putting in place a high risk of cardiovascular problems.
Chronic Kidney Disease: Causes the aggravation of complications and may also lead to deterioration of state.
Ochronosis: Ochronotic Arthropathy: Like in alkaptonuria the joint problems are related to ochronosis.
Skin Changes: The tissues and skin have a bluish-black hue. Cardiovascular Problems: May be worsened by the complications of ochronosis particularly on the connective tissue.
Associated activity
Acuity of presentation
Alkaptonuria:
Gradual Onset: There are no distinct signs, and the condition becomes apparent with time often in adult hood. Some of the early symptoms are dark colored urine, though at times it might be difficult to spot.
Progressive: This condition worsens after some years and manifests more serious symptoms including arthritis and cardiovascular diseases.
Ochronosis:
Progressive Discoloration: Connective tissue and bluish- black pigmentation of the skin of the limbs slowly increases with the progression of the disease.
Chronic Issues: The pigmentation with time deepens and is accompanied by joint complications depending on the effectiveness of the treatment of the alkaptonuria.
Differential Diagnoses
Exogenous Ochronosis
Argyria
Rheumatoid arthritis
Wilson’s Disease
Hemochromatosis
Ehlers-Danlos Syndrome
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Dietary Management:
Restriction of Phenylalanine and Tyrosine: Adopt a low-phenylalanine, low-butyrate, low-isoleucine, and low-leucine diet to minimize formation of homogentisic acid. This may help to prevent further worsening of symptoms.
Pharmacological Treatment:
Nitisinone: This drug has negative effect on enzyme 4-hydroxyphenylpyruvate dioxygenase, which is involved in the catabolism of tyrosine, and decrease the accumulation of homogentisic acid. It was effective in the reduction of urinary HGA levels and had a beneficial effect for slowing the progression of the disease.
Symptomatic Management:
Pain Management: Prescribe anti-inflammatory drugs or other small analgesics for management of common joint pains and inflammation.
Physical Therapy: Perform some of the exercises and physical therapy for the preservation of the joint and movements.
Surgical Interventions:
Joint Replacement Surgery: When shoulder joint is severely damaged or the person is suffering from arthritis, then the person might have to undergo a surgery where the damaged joint is replaced with an artificial joint.
Monitoring and Management of Complications:
Cardiovascular Health: It also includes regular check-ups with cardiovascular symptoms and treatment in case they are detected. Kidney Function: Closely observe the kidney function because chronic kidney disease will speed up complications.
Surgical Interventions:
Arthroplasty: In such cases, surgery may be necessary including corrective osteotomy for joint malunion or degenerative joint diseases.
Preventive Measures:
Avoidance of Exogenous Agents: In case of exogenous ochronosis one should avoid the agents that are responsible for the pigmentation change such as skin-lightening products.
Dietary Management: To decrease homogentisic acid synthesis, stick to low phenylalanine and tyrosine foods with the help of a dietician. Physical Therapy: Physical activity which can include exercises and rehabilitations is useful in preserving joint movement, minimizing pain and arthritis. Prescribe orthotic devices such as braces for those joints which are experienced by the patient.
Lifestyle Modifications: Try and keep your weight within a healthy range for your body to ease the pressure on your joints and ensure that when moving on those joints protect them from and stress to which they may be subjected.
Joint Care: Endure exercises to enable freedom of movement of the affected joint, reduction of its rigidity as well as strengthening of muscles around the area. Employ assistive technology to enhance the movement and to minimize the pain.
Skin Care: It is strongly advised to prevent more skin changes by putting on sunscreen and appropriate clothing. To prevent secondary infections, wash the skin regularly to avoid accumulation of bacteria and other pathogens. Preventive Measures: Do not use external agents like skin-bleaching agents if one is experiencing exogenous ochronosis, as this could worsen pigmentation.
Role of Nitisinone in the treatment of Alkaptonuria
Nitisinone is an orally active drug employed for the treatment of alkaptonuria, which is an inheritable disorder resulting from the deficiency of homogentisic acid oxidase and cope with the accumulation of Homogentisic acid (HGA). It acts as an antagonist to 4-hydroxyphenylpyruvate dioxygenase an important enzyme in the metabolic pathway that catabolises tyrosine into homogentisic acid. It is administered orally. Typically, the starting dose is 2mg once daily but depending on patient response and side effects the dose can be titrated up or down. It is preferably administered in divided doses; the doses are usually two per day.
Joint Replacement Surgery: Ochronosis mainly manifests in joints and large ones are most often affected including the hip and knee joints and it causes ostenostis, arthritis and restricted movement. Arthroplasty or joint replacement surgery involves replacing the joint with artificial ones and is useful when joint pain is extreme and movement limited due to severe joint damage.
Spinal Surgery: It may cause degenerative changes in the intervertebral discs which may lead to pain and compromised mobility. At the advanced stages, patients may need to undergo spinal decompression, or spinal fusion surgeries, to stabilize the spine, and eliminate pain.
Cardiac Valve Replacement: Homogentisic acid in ochronosis can also settle on the heart valves to form calcified nodules which result to dysfunction of the valves, most commonly the aortic. Valve replacement surgery may be in indications if valve dysfunction gets to an advanced level.
The treatment of Ochronosis and Alkaptonuria can be divided into stages in accordance with advancement of the diseases. In the early phase, it involves identifying the disease, genetic counselling and preventive measures which include starting nitisinone and avoidance of foods that increases formation of homogentisic acid. The symptomatic phase entails treating joint pain with NSAIDs, muscular strengthening exercises, and the observance of cardiovascular and renal conditions. The advanced phase involves operations like joint replacement or cardiological valve operations as the initial signs show signs of deterioration. The long-term phase focuses on palliative care, pain control, and physical therapy. The final stage known as the emerging therapies comprises the future solutions offered such as gene therapy or superior pharmacology for the root cause of the disease.
Ochronosis and alkaptonuria is a related condition that results from the inability to metabolise amino acids and hence the buildup of homogentisic acid. Ochronosis is the state which is manifested in bluish or black coloration of connective tissues because of accumulation of homogentisic acid. Alkaptonuria is a very rare inherited metabolic disease which is an autosomal recessive trait that is due to the deficiency of the enzyme homogentisate 1,2-dioxygenase. This enzyme played an important role in the breakdown of Tyrosine and Phenylalanine amino acids. This deficiency results in deposition of homogentisic acid that is later excreted through urine.
Alkaptonuria is a rare genetic disorder that is inherited through autosomal recessive mode, with an incidence of 1 in a million. The disease is spread all over the world with the highest incidence rate recorded in Slovakia and Dominican Republic impacting about one in 19,000 population. Though alkaptonuria can occur in anyone, irrespective of the color of their skin, exogenous ochronosis which is brought about using cosmetic products that lighten the skin such as hydroquinine is more prevalent in the African and Afro-Caribbean zones.
The condition is common in male and female in equal proportion. It is congenital, and it is normally diagnosed when the diapers are discolored blue. However up to 25% of those with alkaptonuria do not show the dark urine staining and hence are usually diagnosed later in life.
Alkaptonuria is characterized by decolorization of connective tissues following in addition to the yellowish or ochre hue termed by Virchow as Ochronosis. Alkaptonuria is a very rare metabolic disease which is an autosomal recessive trait caused by deficiency of homogentisic acid oxidase an enzyme which is responsible for phenylalanine and tyrosine catabolism. This results in the build-up of homogentisic acid in cartilage which gives a bluish-black colour to the affected area. During the development of this process, tensile forces lead to the accumulation of stress on connective tissues causing inflammation, degenerative process and osteoarthritis.
Ochronosis is a result of oxidation of the accumulated homogentisic acid in connective tissues because of alkaptonuria. This deposition occurs out of lack of homogentisic acid oxidase in genetic process and it causes tissues a bluish-black color. Alkaptonuria is an autosomal recessive disease, which results due to deficiency of homogentisic acid oxidase. It also affects the sheer breakdown of homogentisic acid, and this leads to accumulation of homogentisic acid and deposition in tissues.
Life expectancy in alkaptonuria patients is normal but there may be severe arthritic complications, cardiovascular diseases, and change of color of the skin known as ochronosis. This condition can further exacerbate the mentioned complications in chronic kidney disease. The condition is primarily due to the deficiency of homogentisic acid (HGA) oxidase and is characterized by high levels of HGA. This results into blue-black pigmentation of the skin, particularly in the connective tissues and leads to darkening of urine. Accumulation of HGA destroys collagen which triggers arthritis and joint breakdown, particularly in large joints. Further, changes can occur at the structural level of blood vessels and these changes can trigger cardiovascular problems. HGA becomes dark on exposure to air and in presence of alkalis but it may not be very dark colored in acidic urine.
Age Group
Alkaptonuria:
Infancy: It is a congenital condition, but manifestation of the different symptoms may not be observed right from birth.
30s-40s: This is the time that patients start complaining of pains in the joints as well as dark urine.
50s-60s: Consequently, severe complications those include arthritis and ochronosis may tend to aggravate in this age range.
Ochronosis: Typically Seen in Adulthood: Connective tissue and cartilage are also involved bluish-black pigmentation that forms middle age or later and in patients with established alkaptonuria.
Ochronosis:
Skin: Bluish-black discoloration, especially in areas exposed to sunlight.
Cartilage: Bluish-black pigmentation in cartilage (e.g., nose, ears).
Joints: Signs of arthritis, particularly in larger joints; possible early calcification and disc narrowing.
Alkaptonuria:
Urine: Dark-colored urine that turns black upon standing.
Joints: Joint pain, swelling, and deformity, with early calcification and degeneration, especially in larger joints.
Skin: Possible bluish-black pigmentation in connective tissues (similar to ochronosis).
Alkaptonuria:
Arthritis: Ochronotic arthropathy tends to involve the larger weight-bearing joints and the changes are characterized by early calcification and degenerative process.
Cardiovascular Disease: This leads to changes in vessel walls also putting in place a high risk of cardiovascular problems.
Chronic Kidney Disease: Causes the aggravation of complications and may also lead to deterioration of state.
Ochronosis: Ochronotic Arthropathy: Like in alkaptonuria the joint problems are related to ochronosis.
Skin Changes: The tissues and skin have a bluish-black hue. Cardiovascular Problems: May be worsened by the complications of ochronosis particularly on the connective tissue.
Alkaptonuria:
Gradual Onset: There are no distinct signs, and the condition becomes apparent with time often in adult hood. Some of the early symptoms are dark colored urine, though at times it might be difficult to spot.
Progressive: This condition worsens after some years and manifests more serious symptoms including arthritis and cardiovascular diseases.
Ochronosis:
Progressive Discoloration: Connective tissue and bluish- black pigmentation of the skin of the limbs slowly increases with the progression of the disease.
Chronic Issues: The pigmentation with time deepens and is accompanied by joint complications depending on the effectiveness of the treatment of the alkaptonuria.
Exogenous Ochronosis
Argyria
Rheumatoid arthritis
Wilson’s Disease
Hemochromatosis
Ehlers-Danlos Syndrome
Dietary Management:
Restriction of Phenylalanine and Tyrosine: Adopt a low-phenylalanine, low-butyrate, low-isoleucine, and low-leucine diet to minimize formation of homogentisic acid. This may help to prevent further worsening of symptoms.
Pharmacological Treatment:
Nitisinone: This drug has negative effect on enzyme 4-hydroxyphenylpyruvate dioxygenase, which is involved in the catabolism of tyrosine, and decrease the accumulation of homogentisic acid. It was effective in the reduction of urinary HGA levels and had a beneficial effect for slowing the progression of the disease.
Symptomatic Management:
Pain Management: Prescribe anti-inflammatory drugs or other small analgesics for management of common joint pains and inflammation.
Physical Therapy: Perform some of the exercises and physical therapy for the preservation of the joint and movements.
Surgical Interventions:
Joint Replacement Surgery: When shoulder joint is severely damaged or the person is suffering from arthritis, then the person might have to undergo a surgery where the damaged joint is replaced with an artificial joint.
Monitoring and Management of Complications:
Cardiovascular Health: It also includes regular check-ups with cardiovascular symptoms and treatment in case they are detected. Kidney Function: Closely observe the kidney function because chronic kidney disease will speed up complications.
Surgical Interventions:
Arthroplasty: In such cases, surgery may be necessary including corrective osteotomy for joint malunion or degenerative joint diseases.
Preventive Measures:
Avoidance of Exogenous Agents: In case of exogenous ochronosis one should avoid the agents that are responsible for the pigmentation change such as skin-lightening products.
Dermatology, General
Dietary Management: To decrease homogentisic acid synthesis, stick to low phenylalanine and tyrosine foods with the help of a dietician. Physical Therapy: Physical activity which can include exercises and rehabilitations is useful in preserving joint movement, minimizing pain and arthritis. Prescribe orthotic devices such as braces for those joints which are experienced by the patient.
Lifestyle Modifications: Try and keep your weight within a healthy range for your body to ease the pressure on your joints and ensure that when moving on those joints protect them from and stress to which they may be subjected.
Joint Care: Endure exercises to enable freedom of movement of the affected joint, reduction of its rigidity as well as strengthening of muscles around the area. Employ assistive technology to enhance the movement and to minimize the pain.
Skin Care: It is strongly advised to prevent more skin changes by putting on sunscreen and appropriate clothing. To prevent secondary infections, wash the skin regularly to avoid accumulation of bacteria and other pathogens. Preventive Measures: Do not use external agents like skin-bleaching agents if one is experiencing exogenous ochronosis, as this could worsen pigmentation.
Dermatology, General
Nitisinone is an orally active drug employed for the treatment of alkaptonuria, which is an inheritable disorder resulting from the deficiency of homogentisic acid oxidase and cope with the accumulation of Homogentisic acid (HGA). It acts as an antagonist to 4-hydroxyphenylpyruvate dioxygenase an important enzyme in the metabolic pathway that catabolises tyrosine into homogentisic acid. It is administered orally. Typically, the starting dose is 2mg once daily but depending on patient response and side effects the dose can be titrated up or down. It is preferably administered in divided doses; the doses are usually two per day.
Dermatology, General
Joint Replacement Surgery: Ochronosis mainly manifests in joints and large ones are most often affected including the hip and knee joints and it causes ostenostis, arthritis and restricted movement. Arthroplasty or joint replacement surgery involves replacing the joint with artificial ones and is useful when joint pain is extreme and movement limited due to severe joint damage.
Spinal Surgery: It may cause degenerative changes in the intervertebral discs which may lead to pain and compromised mobility. At the advanced stages, patients may need to undergo spinal decompression, or spinal fusion surgeries, to stabilize the spine, and eliminate pain.
Cardiac Valve Replacement: Homogentisic acid in ochronosis can also settle on the heart valves to form calcified nodules which result to dysfunction of the valves, most commonly the aortic. Valve replacement surgery may be in indications if valve dysfunction gets to an advanced level.
Dermatology, General
The treatment of Ochronosis and Alkaptonuria can be divided into stages in accordance with advancement of the diseases. In the early phase, it involves identifying the disease, genetic counselling and preventive measures which include starting nitisinone and avoidance of foods that increases formation of homogentisic acid. The symptomatic phase entails treating joint pain with NSAIDs, muscular strengthening exercises, and the observance of cardiovascular and renal conditions. The advanced phase involves operations like joint replacement or cardiological valve operations as the initial signs show signs of deterioration. The long-term phase focuses on palliative care, pain control, and physical therapy. The final stage known as the emerging therapies comprises the future solutions offered such as gene therapy or superior pharmacology for the root cause of the disease.
Ochronosis and alkaptonuria is a related condition that results from the inability to metabolise amino acids and hence the buildup of homogentisic acid. Ochronosis is the state which is manifested in bluish or black coloration of connective tissues because of accumulation of homogentisic acid. Alkaptonuria is a very rare inherited metabolic disease which is an autosomal recessive trait that is due to the deficiency of the enzyme homogentisate 1,2-dioxygenase. This enzyme played an important role in the breakdown of Tyrosine and Phenylalanine amino acids. This deficiency results in deposition of homogentisic acid that is later excreted through urine.
Alkaptonuria is a rare genetic disorder that is inherited through autosomal recessive mode, with an incidence of 1 in a million. The disease is spread all over the world with the highest incidence rate recorded in Slovakia and Dominican Republic impacting about one in 19,000 population. Though alkaptonuria can occur in anyone, irrespective of the color of their skin, exogenous ochronosis which is brought about using cosmetic products that lighten the skin such as hydroquinine is more prevalent in the African and Afro-Caribbean zones.
The condition is common in male and female in equal proportion. It is congenital, and it is normally diagnosed when the diapers are discolored blue. However up to 25% of those with alkaptonuria do not show the dark urine staining and hence are usually diagnosed later in life.
Alkaptonuria is characterized by decolorization of connective tissues following in addition to the yellowish or ochre hue termed by Virchow as Ochronosis. Alkaptonuria is a very rare metabolic disease which is an autosomal recessive trait caused by deficiency of homogentisic acid oxidase an enzyme which is responsible for phenylalanine and tyrosine catabolism. This results in the build-up of homogentisic acid in cartilage which gives a bluish-black colour to the affected area. During the development of this process, tensile forces lead to the accumulation of stress on connective tissues causing inflammation, degenerative process and osteoarthritis.
Ochronosis is a result of oxidation of the accumulated homogentisic acid in connective tissues because of alkaptonuria. This deposition occurs out of lack of homogentisic acid oxidase in genetic process and it causes tissues a bluish-black color. Alkaptonuria is an autosomal recessive disease, which results due to deficiency of homogentisic acid oxidase. It also affects the sheer breakdown of homogentisic acid, and this leads to accumulation of homogentisic acid and deposition in tissues.
Life expectancy in alkaptonuria patients is normal but there may be severe arthritic complications, cardiovascular diseases, and change of color of the skin known as ochronosis. This condition can further exacerbate the mentioned complications in chronic kidney disease. The condition is primarily due to the deficiency of homogentisic acid (HGA) oxidase and is characterized by high levels of HGA. This results into blue-black pigmentation of the skin, particularly in the connective tissues and leads to darkening of urine. Accumulation of HGA destroys collagen which triggers arthritis and joint breakdown, particularly in large joints. Further, changes can occur at the structural level of blood vessels and these changes can trigger cardiovascular problems. HGA becomes dark on exposure to air and in presence of alkalis but it may not be very dark colored in acidic urine.
Age Group
Alkaptonuria:
Infancy: It is a congenital condition, but manifestation of the different symptoms may not be observed right from birth.
30s-40s: This is the time that patients start complaining of pains in the joints as well as dark urine.
50s-60s: Consequently, severe complications those include arthritis and ochronosis may tend to aggravate in this age range.
Ochronosis: Typically Seen in Adulthood: Connective tissue and cartilage are also involved bluish-black pigmentation that forms middle age or later and in patients with established alkaptonuria.
Ochronosis:
Skin: Bluish-black discoloration, especially in areas exposed to sunlight.
Cartilage: Bluish-black pigmentation in cartilage (e.g., nose, ears).
Joints: Signs of arthritis, particularly in larger joints; possible early calcification and disc narrowing.
Alkaptonuria:
Urine: Dark-colored urine that turns black upon standing.
Joints: Joint pain, swelling, and deformity, with early calcification and degeneration, especially in larger joints.
Skin: Possible bluish-black pigmentation in connective tissues (similar to ochronosis).
Alkaptonuria:
Arthritis: Ochronotic arthropathy tends to involve the larger weight-bearing joints and the changes are characterized by early calcification and degenerative process.
Cardiovascular Disease: This leads to changes in vessel walls also putting in place a high risk of cardiovascular problems.
Chronic Kidney Disease: Causes the aggravation of complications and may also lead to deterioration of state.
Ochronosis: Ochronotic Arthropathy: Like in alkaptonuria the joint problems are related to ochronosis.
Skin Changes: The tissues and skin have a bluish-black hue. Cardiovascular Problems: May be worsened by the complications of ochronosis particularly on the connective tissue.
Alkaptonuria:
Gradual Onset: There are no distinct signs, and the condition becomes apparent with time often in adult hood. Some of the early symptoms are dark colored urine, though at times it might be difficult to spot.
Progressive: This condition worsens after some years and manifests more serious symptoms including arthritis and cardiovascular diseases.
Ochronosis:
Progressive Discoloration: Connective tissue and bluish- black pigmentation of the skin of the limbs slowly increases with the progression of the disease.
Chronic Issues: The pigmentation with time deepens and is accompanied by joint complications depending on the effectiveness of the treatment of the alkaptonuria.
Exogenous Ochronosis
Argyria
Rheumatoid arthritis
Wilson’s Disease
Hemochromatosis
Ehlers-Danlos Syndrome
Dietary Management:
Restriction of Phenylalanine and Tyrosine: Adopt a low-phenylalanine, low-butyrate, low-isoleucine, and low-leucine diet to minimize formation of homogentisic acid. This may help to prevent further worsening of symptoms.
Pharmacological Treatment:
Nitisinone: This drug has negative effect on enzyme 4-hydroxyphenylpyruvate dioxygenase, which is involved in the catabolism of tyrosine, and decrease the accumulation of homogentisic acid. It was effective in the reduction of urinary HGA levels and had a beneficial effect for slowing the progression of the disease.
Symptomatic Management:
Pain Management: Prescribe anti-inflammatory drugs or other small analgesics for management of common joint pains and inflammation.
Physical Therapy: Perform some of the exercises and physical therapy for the preservation of the joint and movements.
Surgical Interventions:
Joint Replacement Surgery: When shoulder joint is severely damaged or the person is suffering from arthritis, then the person might have to undergo a surgery where the damaged joint is replaced with an artificial joint.
Monitoring and Management of Complications:
Cardiovascular Health: It also includes regular check-ups with cardiovascular symptoms and treatment in case they are detected. Kidney Function: Closely observe the kidney function because chronic kidney disease will speed up complications.
Surgical Interventions:
Arthroplasty: In such cases, surgery may be necessary including corrective osteotomy for joint malunion or degenerative joint diseases.
Preventive Measures:
Avoidance of Exogenous Agents: In case of exogenous ochronosis one should avoid the agents that are responsible for the pigmentation change such as skin-lightening products.
Dermatology, General
Dietary Management: To decrease homogentisic acid synthesis, stick to low phenylalanine and tyrosine foods with the help of a dietician. Physical Therapy: Physical activity which can include exercises and rehabilitations is useful in preserving joint movement, minimizing pain and arthritis. Prescribe orthotic devices such as braces for those joints which are experienced by the patient.
Lifestyle Modifications: Try and keep your weight within a healthy range for your body to ease the pressure on your joints and ensure that when moving on those joints protect them from and stress to which they may be subjected.
Joint Care: Endure exercises to enable freedom of movement of the affected joint, reduction of its rigidity as well as strengthening of muscles around the area. Employ assistive technology to enhance the movement and to minimize the pain.
Skin Care: It is strongly advised to prevent more skin changes by putting on sunscreen and appropriate clothing. To prevent secondary infections, wash the skin regularly to avoid accumulation of bacteria and other pathogens. Preventive Measures: Do not use external agents like skin-bleaching agents if one is experiencing exogenous ochronosis, as this could worsen pigmentation.
Dermatology, General
Nitisinone is an orally active drug employed for the treatment of alkaptonuria, which is an inheritable disorder resulting from the deficiency of homogentisic acid oxidase and cope with the accumulation of Homogentisic acid (HGA). It acts as an antagonist to 4-hydroxyphenylpyruvate dioxygenase an important enzyme in the metabolic pathway that catabolises tyrosine into homogentisic acid. It is administered orally. Typically, the starting dose is 2mg once daily but depending on patient response and side effects the dose can be titrated up or down. It is preferably administered in divided doses; the doses are usually two per day.
Dermatology, General
Joint Replacement Surgery: Ochronosis mainly manifests in joints and large ones are most often affected including the hip and knee joints and it causes ostenostis, arthritis and restricted movement. Arthroplasty or joint replacement surgery involves replacing the joint with artificial ones and is useful when joint pain is extreme and movement limited due to severe joint damage.
Spinal Surgery: It may cause degenerative changes in the intervertebral discs which may lead to pain and compromised mobility. At the advanced stages, patients may need to undergo spinal decompression, or spinal fusion surgeries, to stabilize the spine, and eliminate pain.
Cardiac Valve Replacement: Homogentisic acid in ochronosis can also settle on the heart valves to form calcified nodules which result to dysfunction of the valves, most commonly the aortic. Valve replacement surgery may be in indications if valve dysfunction gets to an advanced level.
Dermatology, General
The treatment of Ochronosis and Alkaptonuria can be divided into stages in accordance with advancement of the diseases. In the early phase, it involves identifying the disease, genetic counselling and preventive measures which include starting nitisinone and avoidance of foods that increases formation of homogentisic acid. The symptomatic phase entails treating joint pain with NSAIDs, muscular strengthening exercises, and the observance of cardiovascular and renal conditions. The advanced phase involves operations like joint replacement or cardiological valve operations as the initial signs show signs of deterioration. The long-term phase focuses on palliative care, pain control, and physical therapy. The final stage known as the emerging therapies comprises the future solutions offered such as gene therapy or superior pharmacology for the root cause of the disease.
Both our subscription plans include Free CME/CPD AMA PRA Category 1 credits.
Digital Certificate PDF
On course completion, you will receive a full-sized presentation quality digital certificate.
medtigo Simulation
A dynamic medical simulation platform designed to train healthcare professionals and students to effectively run code situations through an immersive hands-on experience in a live, interactive 3D environment.
medtigo Points
medtigo points is our unique point redemption system created to award users for interacting on our site. These points can be redeemed for special discounts on the medtigo marketplace as well as towards the membership cost itself.
Community Forum post/reply = 5 points
*Redemption of points can occur only through the medtigo marketplace, courses, or simulation system. Money will not be credited to your bank account. 10 points = $1.
All Your Certificates in One Place
When you have your licenses, certificates and CMEs in one place, it's easier to track your career growth. You can easily share these with hospitals as well, using your medtigo app.
