prolidase deficiency

Prolidase deficiency is a rare metabolic disorder characterized by a wide variety of symptoms. The disorder typically becomes apparent during infancy.

• Skin lesions: Affected individuals may experience severe, chronic, and painful skin ulcers on the lower extremities and telangiectasias (small dilated blood vessels) on the face and hands [1][11].
• Recurrent infections: Prolidase deficiency can lead to recurrent infections, particularly of the skin and respiratory tract [1][11].
• Dysmorphic facial features: Individuals with this condition may have unusual facial features, such as low anterior and posterior hairline, hypertelorism (increased distance between the eyes), proptosis (bulging eyes), flat nasal bridge, thin vermilion of the upper lip, and other abnormalities [13].
• Variable intellectual disability: Prolidase deficiency can result in variable intellectual disability, ranging from mild to severe cognitive impairment [1][11].
• Organomegaly: Affected individuals may experience enlargement of the spleen (splenomegaly) and liver (hepatomegaly), with elevated liver enzymes [4][14].

Prolidase deficiency is a rare autosomal recessive disorder caused by mutations in the PEPD gene, which encodes for the enzyme prolidase. This enzyme plays a crucial role in collagen metabolism, and its deficiency leads to skin fragility and recurrent ulceration [6]. The condition can present in infancy with splenomegaly, diarrhea, vomiting, and dehydration, and may also be associated with developmental delay and recurrent infections [9].

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Prolidase deficiency, a rare autosomal recessive inborn metabolic and multisystemic disease, presents with a variety of signs and symptoms.

Common Signs and Symptoms:

• Skin lesions: Severe, chronic, recalcitrant, and painful skin ulcers on the lower extremities are a hallmark of prolidase deficiency [6][10].
• Recurrent infections: Frequent infections of the skin or ears, or potentially life-threatening respiratory tract infections can occur [5][10].
• Dysmorphic facial features: Low anterior and posterior hairline, hypertelorism, proptosis, flat nasal bridge, thin vermilion of the upper lip, and prognathism are common facial features associated with prolidase deficiency [2][10].
• Variable cognitive impairment: Intellectual disability can range from mild to severe in individuals with prolidase deficiency [11][14].

Other Signs and Symptoms:

• Splenomegaly: Enlargement of the spleen (splenomegaly) is a common feature, often accompanied by elevated liver enzymes [10][12].
• Telangiectasias: Small dilated blood vessels on the face and hands can be observed in individuals with prolidase deficiency [9][10].
• Autoimmune conditions: An association between prolidase deficiency and autoimmune conditions, such as systemic lupus erythematosus (SLE), has been described [14].

Age of Onset:

• Prolidase deficiency can present in infancy with splenomegaly, diarrhea, vomiting, and dehydration [2].
• Symptoms may also appear later in life, often during childhood or adolescence.

It is essential to note that the clinical manifestations and age of onset are quite variable among individuals with prolidase deficiency.

Treatment Options for Prolidase Deficiency

Prolidase deficiency, a rare metabolic disorder, requires symptomatic and supportive treatment to manage its various symptoms. While there is no definitive cure, several drug treatments have been explored to alleviate the condition's effects.

• Rituximab: This monoclonal antibody has shown promise in treating prolidase deficiency by reducing inflammation and preventing further tissue damage [1][2]. In one case study, rituximab treatment led to sustained recession of mucocutaneous ulceration, enabling tapering of steroids [3].
• Anticoagulants: Successful treatment with anticoagulants has been reported in cases of ulceration associated with prolidase deficiency [4].
• Corticosteroids: Corticosteroid treatment may be employed to manage inflammation and reduce symptoms [5].
• Immunosuppressive drugs: In some cases, immunosuppressive drugs have been used to treat the condition, particularly when there are signs of an autoimmune disorder [6].

Current Treatment Limitations

While these treatments can provide relief from symptoms, it's essential to note that prolidase deficiency is a complex condition with no definitive cure. Most treatment strategies aim to replace prolidase or treat and stop ulcerative progression.

• L-proline topical application: Topical application of L-proline has been used in some cases, but its effectiveness is still being explored [7].
• Multidirectional drug treatment: In severe cases, multidirectional drug treatment and supportive therapies may be necessary to manage the condition's various symptoms [8].

Future Research Directions

Further research is needed to develop more effective treatments for prolidase deficiency. Understanding the genetic basis of this disorder will help identify potential therapeutic targets.

References:

[1] F Atschekzei · 2023 · Cited by 2 — Rituximab to treat prolidase deficiency due to a novel pathogenic copy number variation in PEPD. [2] F Atschekzei · 2023 · Cited by 2 — Rituximab to treat prolidase deficiency due to a novel pathogenic copy number variation in PEPD. [3] Ulceration in Prolidase Deficiency: Successful Treatment with Anticoagulants. Acta Derm Venereol. 2020 Jan 7;100(1):adv00002. doi: 10.2340/00015555-3324. [4] Yasuda K, Ogata K, Kariya K et al (1999) Corticosteroid treatment of prolidase deficiency. [5] Prolidase deficiency is a rare recessive disorder caused by mutations in the prolidase gene and characterized by severe skin lesions. The use of prodrugs in the treatment of various tumors has been recently successfully employed to achieve specific drug delivery. [6] Kira et al (2020) Ulceration in Prolidase Deficiency: Successful Treatment with Anticoagulants. [7] Yasuda K, Ogata K, Kariya K et al (1999) Corticosteroid treatment of prolidase deficiency. [8] 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, also known as hyperimidodipeptiduria, is a rare autosomal recessive inborn metabolic and multisystemic disease. When considering the differential diagnosis for this condition, several other conditions should be taken into account.

• Werner syndrome: This is a rare genetic disorder characterized by premature aging, which can manifest with skin lesions similar to those seen in prolidase deficiency.
• Beta-thalassemia: A genetic disorder affecting hemoglobin production, leading to anemia and potentially skin lesions.
• Vasculitis: Inflammation of the blood vessels, which can cause skin lesions and ulcers.
• Autosomal dominant and recessive forms of hyper-IgE syndrome: These are rare genetic disorders characterized by recurrent skin infections, eczema, and elevated IgE levels.

These conditions should be considered in the differential diagnosis for prolidase deficiency, as they share similar symptoms such as skin lesions and ulcers. However, it's essential to note that only around a third of patients with prolidase deficiency have skin ulcers at any given time [7].

The diagnosis of prolidase deficiency is typically confirmed by detecting biallelic PEPD pathogenic variants or reduced prolidase enzyme activity in patients presenting with characteristic symptoms [5].