Prolidase deficiency: Difference between revisions
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{{Infobox medical condition | |||
| name = Prolidase deficiency | |||
| image = [[File:Protein_PEPD_PDB_2iw2.png|alt=Structure of the PEPD protein]] | |||
| caption = Structure of the PEPD protein | |||
| synonyms = Hyper-Iminodipeptiduria | |||
| pronounce = | |||
| specialty = [[Genetics]], [[Metabolism]] | |||
| symptoms = [[Skin ulcers]], [[Developmental delay]], [[Recurrent infections]], [[Facial dysmorphism]] | |||
| onset = [[Infancy]] or [[childhood]] | |||
| duration = [[Chronic]] | |||
| causes = Mutations in the [[PEPD]] gene | |||
| risks = | |||
| diagnosis = [[Genetic testing]], [[Clinical evaluation]] | |||
| differential = [[Lysosomal storage disorders]], [[Connective tissue disorders]] | |||
| prevention = | |||
| treatment = [[Supportive care]], [[Antibiotics]] for infections | |||
| medication = | |||
| prognosis = Variable, can be severe | |||
| frequency = Rare | |||
| deaths = | |||
}} | |||
== '''Alternate names''' == | == '''Alternate names''' == | ||
Hyperimidodipeptiduria; Imidodipeptidase deficiency; Peptidase deficiency; PD | Hyperimidodipeptiduria; Imidodipeptidase deficiency; Peptidase deficiency; PD | ||
== '''Definition''' == | == '''Definition''' == | ||
Prolidase deficiency is a rare metabolic condition characterized by skin [[lesions]], recurrent infections, unusual facial features, variable intellectual disability, enlargement of the liver ([[hepatomegaly]]) with elevated liver enzymes, and enlargement of the spleen ([[splenomegaly]]). | Prolidase deficiency is a rare metabolic condition characterized by skin [[lesions]], recurrent infections, unusual facial features, variable intellectual disability, enlargement of the liver ([[hepatomegaly]]) with elevated liver enzymes, and enlargement of the spleen ([[splenomegaly]]). | ||
== '''Epidemiology''' == | == '''Epidemiology''' == | ||
Prolidase deficiency is a rare disorder. Approximately 70 individuals with this disorder have been documented in the medical literature, and researchers have estimated that the condition occurs in approximately 1 in 1 million to 1 in 2 million newborns. It is more common in certain areas in northern Israel, both among members of a religious minority called the Druze and in nearby Arab Moslem populations. | Prolidase deficiency is a rare disorder. Approximately 70 individuals with this disorder have been documented in the medical literature, and researchers have estimated that the condition occurs in approximately 1 in 1 million to 1 in 2 million newborns. It is more common in certain areas in northern Israel, both among members of a religious minority called the Druze and in nearby Arab Moslem populations. | ||
== '''Cause''' == | == '''Cause''' == | ||
[[File:Prolidase cleavage of peptide to yield alanine and proline.png|thumb]] | [[File:Prolidase cleavage of peptide to yield alanine and proline.png|left|thumb]] | ||
Prolidase deficiency is caused by mutations in the '''PEPD gene'''. This gene provides instructions for making the enzyme '''prolidase''', also called peptidase D. Prolidase helps divide certain [[dipeptides]], which are molecules composed of two protein building blocks (amino acids). Specifically, prolidase divides dipeptides containing the amino acids [[proline]] or [[hydroxyproline]]. By freeing these amino acids, prolidase helps make them available for use in producing proteins that the body needs. | Prolidase deficiency is caused by mutations in the '''PEPD gene'''. This gene provides instructions for making the enzyme '''prolidase''', also called peptidase D. Prolidase helps divide certain [[dipeptides]], which are molecules composed of two protein building blocks (amino acids). Specifically, prolidase divides dipeptides containing the amino acids [[proline]] or [[hydroxyproline]]. By freeing these amino acids, prolidase helps make them available for use in producing proteins that the body needs. | ||
Prolidase is also involved in the final step of the breakdown of some proteins obtained through the diet and proteins that are no longer needed in the body. Prolidase is particularly important in the breakdown of [[collagens]], a family of proteins that are rich in proline and hydroxyproline. Collagens are an important part of the extracellular matrix, which is the lattice of proteins and other molecules outside the cell. The extracellular matrix strengthens and supports connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Collagen breakdown occurs during the maintenance (remodeling) of the extracellular matrix. | Prolidase is also involved in the final step of the breakdown of some proteins obtained through the diet and proteins that are no longer needed in the body. Prolidase is particularly important in the breakdown of [[collagens]], a family of proteins that are rich in proline and hydroxyproline. Collagens are an important part of the extracellular matrix, which is the lattice of proteins and other molecules outside the cell. The extracellular matrix strengthens and supports connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Collagen breakdown occurs during the maintenance (remodeling) of the extracellular matrix. | ||
PEPD gene mutations that cause prolidase deficiency result in the '''loss of prolidase enzyme activity'''. It is not well understood how the absence of prolidase activity causes the various signs and symptoms of prolidase deficiency. Researchers have suggested that accumulation of [[dipeptides]] that have not been broken down may lead to cell death. When cells die, their contents are released into the surrounding tissue, which could cause [[inflammation]] and lead to the skin problems seen in prolidase deficiency. Impaired collagen breakdown during remodeling of the extracellular matrix may also contribute to the skin problems. The intellectual disability that occurs in prolidase deficiency might result from problems in processing neuropeptides, which are brain signaling proteins that are rich in [[proline]]. It is unclear how absence of prolidase activity results in the other features of prolidase deficiency. | PEPD gene mutations that cause prolidase deficiency result in the '''loss of prolidase enzyme activity'''. It is not well understood how the absence of prolidase activity causes the various signs and symptoms of prolidase deficiency. Researchers have suggested that accumulation of [[dipeptides]] that have not been broken down may lead to cell death. When cells die, their contents are released into the surrounding tissue, which could cause [[inflammation]] and lead to the skin problems seen in prolidase deficiency. Impaired collagen breakdown during remodeling of the extracellular matrix may also contribute to the skin problems. The intellectual disability that occurs in prolidase deficiency might result from problems in processing neuropeptides, which are brain signaling proteins that are rich in [[proline]]. It is unclear how absence of prolidase activity results in the other features of prolidase deficiency. | ||
== '''Inheritance''' == | |||
This condition is inherited in an [[autosomal recessive]] pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | This condition is inherited in an [[autosomal recessive]] pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | ||
== '''Signs and symptoms''' == | == '''Signs and symptoms''' == | ||
Symptoms typically present during infancy and vary greatly among affected individuals. | Symptoms typically present during infancy and vary greatly among affected individuals. | ||
Affected individuals may have enlargement of the spleen ([[splenomegaly]]); in some cases, both the spleen and liver are enlarged ([[hepatosplenomegaly]]). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency are susceptible to severe infections of the skin or ears, or potentially life-threatening respiratory tract infections. Some individuals with prolidase deficiency have chronic lung disease. | Affected individuals may have enlargement of the spleen ([[splenomegaly]]); in some cases, both the spleen and liver are enlarged ([[hepatosplenomegaly]]). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency are susceptible to severe infections of the skin or ears, or potentially life-threatening respiratory tract infections. Some individuals with prolidase deficiency have chronic lung disease. | ||
Characteristic facial features in people with prolidase deficiency include prominent eyes that are widely spaced ([[hypertelorism]]), a high forehead, a flat bridge of the nose, and a very small lower jaw and chin ([[micrognathia]]). Affected children may experience delayed development, and about 75 percent of people with prolidase deficiency have intellectual disability that may range from mild to severe. | Characteristic facial features in people with prolidase deficiency include prominent eyes that are widely spaced ([[hypertelorism]]), a high forehead, a flat bridge of the nose, and a very small lower jaw and chin ([[micrognathia]]). Affected children may experience delayed development, and about 75 percent of people with prolidase deficiency have intellectual disability that may range from mild to severe. | ||
People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. Skin ulcers, especially on the legs, may not heal completely, resulting in complications including infection and amputation. | People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. Skin ulcers, especially on the legs, may not heal completely, resulting in complications including infection and amputation. | ||
The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Some people with this disorder do not have any symptoms. In these individuals the condition can be detected by laboratory tests such as newborn screening tests or tests offered to relatives of affected individuals. | The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Some people with this disorder do not have any symptoms. In these individuals the condition can be detected by laboratory tests such as newborn screening tests or tests offered to relatives of affected individuals. | ||
For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. | For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. | ||
80%-99% of people have these symptoms | 80%-99% of people have these symptoms | ||
| Line 48: | Line 59: | ||
* Skin ulcer(Open skin sore) | * Skin ulcer(Open skin sore) | ||
* Thin skin | * Thin skin | ||
30%-79% of people have these symptoms | 30%-79% of people have these symptoms | ||
* Abnormal fingernail morphology(Abnormal fingernails) | * Abnormal fingernail morphology(Abnormal fingernails) | ||
| Line 62: | Line 72: | ||
* Visual impairment(Impaired vision) | * Visual impairment(Impaired vision) | ||
* White forelock(White part of hair above forehead) | * White forelock(White part of hair above forehead) | ||
5%-29% of people have these symptoms | 5%-29% of people have these symptoms | ||
* Hepatomegaly(Enlarged liver) | * Hepatomegaly(Enlarged liver) | ||
| Line 71: | Line 80: | ||
* Reduced bone mineral density(Low solidness and mass of the bones | * Reduced bone mineral density(Low solidness and mass of the bones | ||
* Splenomegaly(Increased spleen size) | * Splenomegaly(Increased spleen size) | ||
== '''Diagnosis''' == | == '''Diagnosis''' == | ||
The diagnosis of prolidase deficiency is based on the presence of characteristic clinical symptoms, high levels of [[imidodipeptides]] in the urine, and detection of either mutations in the '''PEPD gene''' or reduced levels of prolidase enzyme activity | The diagnosis of prolidase deficiency is based on the presence of characteristic clinical symptoms, high levels of [[imidodipeptides]] in the urine, and detection of either mutations in the '''PEPD gene''' or reduced levels of prolidase enzyme activity | ||
== '''Treatment''' == | == '''Treatment''' == | ||
There is no cure for prolidase deficiency. Treatment is aimed at treating the specific symptoms present in each individual. A multidisciplinary team of specialists is often needed. Supportive treatment of the skin, lung, and immunologic manifestations has been helpful in some cases. | There is no cure for prolidase deficiency. Treatment is aimed at treating the specific symptoms present in each individual. A multidisciplinary team of specialists is often needed. Supportive treatment of the skin, lung, and immunologic manifestations has been helpful in some cases. | ||
== '''Prognosis''' == | == '''Prognosis''' == | ||
The long-term outlook can vary because of the large possible range of severity in each person. For example, while skin ulcers lead to amputations in some people, others continue to be symptom-free. | The long-term outlook can vary because of the large possible range of severity in each person. For example, while skin ulcers lead to amputations in some people, others continue to be symptom-free. | ||
In most cases, people with prolidase deficiency experience a reduced quality of life because of infections and chronic pulmonary (lung) complications. Life expectancy is often decreased, with infection being the most common cause of death. | In most cases, people with prolidase deficiency experience a reduced quality of life because of infections and chronic pulmonary (lung) complications. Life expectancy is often decreased, with infection being the most common cause of death. | ||
{{Amino acid metabolic pathology}} | {{Amino acid metabolic pathology}} | ||
[[Category:Amino acid metabolism disorders]] | [[Category:Amino acid metabolism disorders]] | ||
[[Category:Autosomal recessive disorders]] | [[Category:Autosomal recessive disorders]] | ||
Latest revision as of 16:01, 8 April 2025
Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
W8MD's medical weight loss NYC, sleep center NYC
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| Prolidase deficiency | |
|---|---|
| Structure of the PEPD protein | |
| Synonyms | Hyper-Iminodipeptiduria |
| Pronounce | |
| Specialty | Genetics, Metabolism |
| Symptoms | Skin ulcers, Developmental delay, Recurrent infections, Facial dysmorphism |
| Complications | N/A |
| Onset | Infancy or childhood |
| Duration | Chronic |
| Types | N/A |
| Causes | Mutations in the PEPD gene |
| Risks | |
| Diagnosis | Genetic testing, Clinical evaluation |
| Differential diagnosis | Lysosomal storage disorders, Connective tissue disorders |
| Prevention | |
| Treatment | Supportive care, Antibiotics for infections |
| Medication | |
| Prognosis | Variable, can be severe |
| Frequency | Rare |
| Deaths | |
Alternate names[edit]
Hyperimidodipeptiduria; Imidodipeptidase deficiency; Peptidase deficiency; PD
Definition[edit]
Prolidase deficiency is a rare metabolic condition characterized by skin lesions, recurrent infections, unusual facial features, variable intellectual disability, enlargement of the liver (hepatomegaly) with elevated liver enzymes, and enlargement of the spleen (splenomegaly).
Epidemiology[edit]
Prolidase deficiency is a rare disorder. Approximately 70 individuals with this disorder have been documented in the medical literature, and researchers have estimated that the condition occurs in approximately 1 in 1 million to 1 in 2 million newborns. It is more common in certain areas in northern Israel, both among members of a religious minority called the Druze and in nearby Arab Moslem populations.
Cause[edit]
Prolidase deficiency is caused by mutations in the PEPD gene. This gene provides instructions for making the enzyme prolidase, also called peptidase D. Prolidase helps divide certain dipeptides, which are molecules composed of two protein building blocks (amino acids). Specifically, prolidase divides dipeptides containing the amino acids proline or hydroxyproline. By freeing these amino acids, prolidase helps make them available for use in producing proteins that the body needs. Prolidase is also involved in the final step of the breakdown of some proteins obtained through the diet and proteins that are no longer needed in the body. Prolidase is particularly important in the breakdown of collagens, a family of proteins that are rich in proline and hydroxyproline. Collagens are an important part of the extracellular matrix, which is the lattice of proteins and other molecules outside the cell. The extracellular matrix strengthens and supports connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Collagen breakdown occurs during the maintenance (remodeling) of the extracellular matrix. PEPD gene mutations that cause prolidase deficiency result in the loss of prolidase enzyme activity. It is not well understood how the absence of prolidase activity causes the various signs and symptoms of prolidase deficiency. Researchers have suggested that accumulation of dipeptides that have not been broken down may lead to cell death. When cells die, their contents are released into the surrounding tissue, which could cause inflammation and lead to the skin problems seen in prolidase deficiency. Impaired collagen breakdown during remodeling of the extracellular matrix may also contribute to the skin problems. The intellectual disability that occurs in prolidase deficiency might result from problems in processing neuropeptides, which are brain signaling proteins that are rich in proline. It is unclear how absence of prolidase activity results in the other features of prolidase deficiency.
Inheritance[edit]
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Signs and symptoms[edit]
Symptoms typically present during infancy and vary greatly among affected individuals. Affected individuals may have enlargement of the spleen (splenomegaly); in some cases, both the spleen and liver are enlarged (hepatosplenomegaly). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency are susceptible to severe infections of the skin or ears, or potentially life-threatening respiratory tract infections. Some individuals with prolidase deficiency have chronic lung disease. Characteristic facial features in people with prolidase deficiency include prominent eyes that are widely spaced (hypertelorism), a high forehead, a flat bridge of the nose, and a very small lower jaw and chin (micrognathia). Affected children may experience delayed development, and about 75 percent of people with prolidase deficiency have intellectual disability that may range from mild to severe. People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. Skin ulcers, especially on the legs, may not heal completely, resulting in complications including infection and amputation. The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Some people with this disorder do not have any symptoms. In these individuals the condition can be detected by laboratory tests such as newborn screening tests or tests offered to relatives of affected individuals. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms
- Abnormal facial shape(Unusual facial appearance)
- Abnormality of the hip bone(Abnormality of the hips)
- Abnormality of the middle ear
- Carious teeth(Dental cavities)
- Crusting erythematous dermatitis
- Cutaneous photosensitivity
- Depressed nasal bridge(Depressed bridge of nose)
- Dry skin
- Erythema
- Hearing impairment(Deafness)
- Palmoplantar keratoderma(Thickening of palms and soles)
- Papule
- Pruritus(Itching)
- Recurrent respiratory infections(Frequent respiratory infections)
- Skin ulcer(Open skin sore)
- Thin skin
30%-79% of people have these symptoms
- Abnormal fingernail morphology(Abnormal fingernails)
- Abnormality of retinal pigmentation
- Arachnodactyly(Long slender fingers)
- Bilateral single transverse palmar creases
- Depressed nasal ridge(Flat nose)
- Generalized hirsutism(Excessive hairiness over body)
- Genu valgum(Knock knees)
- Hypertelorism(Wide-set eyes)
- Low anterior hairline(Low frontal hairline)
- Micrognathia(Little lower jaw)
- Visual impairment(Impaired vision)
- White forelock(White part of hair above forehead)
5%-29% of people have these symptoms
- Hepatomegaly(Enlarged liver)
- Hypoplasia of the zygomatic bone(Cheekbone underdevelopment)
- Intellectual disability(Mental deficiency)
- Proptosis(Bulging eye)
- Recurrent cystitis(Recurrent bladder infections)
- Reduced bone mineral density(Low solidness and mass of the bones
- Splenomegaly(Increased spleen size)
Diagnosis[edit]
The diagnosis of prolidase deficiency is based on the presence of characteristic clinical symptoms, high levels of imidodipeptides in the urine, and detection of either mutations in the PEPD gene or reduced levels of prolidase enzyme activity
Treatment[edit]
There is no cure for prolidase deficiency. Treatment is aimed at treating the specific symptoms present in each individual. A multidisciplinary team of specialists is often needed. Supportive treatment of the skin, lung, and immunologic manifestations has been helpful in some cases.
Prognosis[edit]
The long-term outlook can vary because of the large possible range of severity in each person. For example, while skin ulcers lead to amputations in some people, others continue to be symptom-free. In most cases, people with prolidase deficiency experience a reduced quality of life because of infections and chronic pulmonary (lung) complications. Life expectancy is often decreased, with infection being the most common cause of death.
| Inborn error of amino acid metabolism | ||||||||||||||||||||||||||||||||||
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NIH genetic and rare disease info[edit]
Prolidase deficiency is a rare disease.
| Rare and genetic diseases | ||||||
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Rare diseases - Prolidase deficiency
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