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Meleda Disease

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Copyright 1996, 1998, 2003, 2004

Synonyms of Meleda Disease

Disorder Subdivisions

General Discussion

Meleda disease is an extremely rare inherited skin disorder characterized by the slowly progressive development of dry, thick patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Affected skin may be unusually red (erythema) and become abnormally thick and scaly (symmetrical cornification). Affected children may also exhibit various abnormalities of the nails; excessive sweating (hyperhidrosis) associated with an unpleasant odor; and/or, in some cases, development of small, firm raised lesions (lichenoid plaques). The range and severity of symptoms may vary from case to case. Meleda disease is inherited as an autosomal recessive trait.

Symptoms

Meleda disease is an extremely rare inherited skin disorder that is usually obvious shortly after birth. Initially, affected infants may have unusually red skin on the palms of the hands and the soles of the feet (palmoplantar erythema). The affected skin then becomes abnormally thick, yellowish-brown, and scale-like (hyperkeratosis). These skin lesions are usually present on both sides of the body (bilateral) on the same respective areas (symmetrical palmoplantar keratosis). As the child grows older, these patches may spread to involve the entire hand or foot. Eventually, the wrists, forearms, and knees may also become involved. In some cases, with advancing age, the skin on the chest and abdomen may also become dry, scaly, and cracked. Excessively dry skin may cause pain and discomfort.

Individuals with Meleda disease may also have unusually red skin around the mouth (perioral erythema). In addition, affected children exhibit various abnormalities of the nails (nail dystrophy). The nails may become excessively hard and thick (pachyonychia); "spoon-shaped" (koilonychia); or "hooked" (onychogryphosis) in appearance. In some cases, affected individuals may also have excessive hair growth on the hands or feet.

Some individuals with Meleda disease may exhibit small, firm raised skin lesions (lichenoid plaques) in areas affected by hyperkeratosis. In addition, in most cases, affected individuals may exhibit excessive sweating (hyperhidrosis) that may be associated with an unpleasant odor. Additional features associated with Meleda disease may include abnormal webbing (fusion) of the fingers and/or toes (syndactyly), abnormal shortening of the fingers and toes (brachydactyly), and/or a grooved, cracked tongue (lingua plicata).

Causes

Meleda disease is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

Some individuals with Meleda disease have had parents who were related by blood (consanguineous). All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Investigators have determined that some cases of Meleda disease may be caused by disruption or changes (mutations) of the ARS gene located on the long arm (q) of chromosome 8 (8q24.3). The ARS gene encodes a protein known as SLURP-1, which researchers believe is involved in cell signaling and adhesion. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes, which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 8q24.3" refers to band 24.3 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Affected Populations

Meleda disease is an extremely rare disorder that affects males and females in equal numbers. More than 100 cases have been reported in the medical literature. The prevalence of Meleda disease in the general population is estimated at one case per 100,000 people. Skin abnormalities associated with this disorder may be present at birth (congenital). Other symptoms usually become apparent by the second or third year of life.

According to the medical literature, Meleda disease was first identified in 1898 among people on the Island of Meleda in Dalmatia, Yugoslavia. Most of the original cases reported of this disorder were from that region. However, in the past 25 years many cases have been reported in various countries.

Related Disorders

Symptoms of the following disorders can be similar to those of Meleda disease. Comparisons may be useful for a differential diagnosis:

Papillon-Lefevre syndrome is an extremely rare inherited disorder characterized by the development of dry scaly patches of skin on the palms of the hands and the soles of the feet (palmar-plantar hyperkeratosis) as well as severe inflammation and degeneration of the structures that surround and support the teeth (periodontium), resulting in premature tooth loss (periodontoclasia). Affected individuals may also have frequent pus-producing (pyogenic) skin infections and abnormalities of the nails (nail dystrophy). They may also perspire heavily and frequently (hyperhidrosis). Papillon-Lefevre syndrome is believed to be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "Papillon Lefevre" as your search term in the Rare Disease Database.)

Cochin Jewish disorder is a rare inherited disorder characterized by the development of red, scaly thickened patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis), frequent pus-producing (pyogenic) skin infections, overgrowth (hypertrophy) of the fingernails and toenails (onychogryphosis), and degeneration of the structures that surround and support the teeth (periodontosis). Periodontosis usually results in the premature loss of teeth. Affected individuals may also have flat feet (pes planus) and abnormally long, slender fingers and toes (arachnodactyly). Most individuals with this disorder experience numbness and tingling and lack normal blood flow to the fingers and/or toes when exposed to cold temperatures. They also often exhibit loss of bone tissue at the ends of the fingers and/or toes (acroosteolysis). Cochin Jewish disorder is thought to be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "Cochin Jewish" as your search term in the Rare Disease Database.)

Mal de Naxos is an extremely rare inherited disorder characterized by the slow progressive development of dry scaly skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Affected skin may be unusually red and become abnormally thick (congenital symmetrical cornification). Affected individuals may also have hair that is curly, rough, and dense. In addition, affected children may exhibit heart (cardiac) defects, such as an abnormally large heart (cardiomegaly). Mal de Naxos is thought to be inherited as an autosomal recessive genetic trait.

Jadassohn-Lewandowsky type pachyonychia congenita is a rare inherited disorder characterized by reddening, dryness, and a scaly appearance of the skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis) and/or overgrowth and malformation of the fingernails and toenails (onychogryphosis). In addition, affected infants may have teeth that are present at birth (neonatal dentition). Additional features may include loss of scalp hair, excessive sweating (hyperhidrosis) of the hands and feet, hoarseness, and/or, in some cases, respiratory distress. Mental retardation may be present in some cases. Jadassohn-Lewandowsky type pachyonychia congenita is thought to be inherited as an autosomal dominant genetic trait.

Keratosis palmaris et plantaris of unna-thost (Greither's disease) is a very rare inherited skin disorder characterized by unusual whitish or yellowish thick patches of skin (keratosis) on the palms of the hands and/or the soles of the feet. Skin lesions stop at the lateral surfaces of the palms of the hands and/or the soles of the feet. In most cases, affected individuals also exhibit excessive sweating (hyperhidrosis) and unusually-shaped, thick nails. Most cases of this disorder are inherited as an autosomal dominant genetic trait; however, a severe autosomal recessive form has not been ruled out.

Standard Therapies

Diagnosis
The diagnosis of Meleda disease may be confirmed by a thorough clinical evaluation that includes a detailed patient history and identification of characteristic physical findings. In most cases, skin abnormalities may be apparent at birth (congenital) or during infancy including characteristic skin abnormalities on the palms of the hands and the soles of the feet.

Treatment
The treatment of Meleda disease is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat skin problems (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.

Limited success has been found in treating associated skin lesions with lotions applied directly to the skin (topical). In some cases, surgery may be used to alleviate skin problems. Excessive sweating (hyperhidrosis) may be treated with aluminum acetate soaks or aluminum chloride hexahydrate applications.

Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Organizations related to Meleda Disease

(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., skin abnormalities, etc.].)

References

TEXTBOOKS
Kelsell DP, Leigh IM, Meleda Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:128.

Behrman RE, ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:1872.

Champion RH, et al., eds. Textbook of Dermatology. 5th ed. Cambridge, MA: Blackwell Scientific Publications; 1992:1376.

Buyce ML., ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:1096.

JOURNAL ARTICLES
Charfeddine C, et al. A novel missense mutation in the gene encoding SLURP-1 in patients with Mal de Meleda from northern Tunisia. Br J Dermatol. 2003;149:1108-15.

Hu G, et al. A recurrent mutation in the ARS (component B) gene encoding SLURP-1 in Turkish families with mal de Meleda: evidence of a founder effect. J Invest Dermatol. 2003;120:967-69.

Ergin S, et al. Mal de Meleda: a new geographical localization in Anatolia. Dermatology. 2003;206:124-30.

Ward KM, et al. Identification of recurrent mutations in the ARS (component B) gene encoding SLURP-1 in two families with mal de Meleda. J Invest Dermatol. 2003;120:96-98.

Marrakchi S, et al. Novel mutations in the gene encoding secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1) and description of five ancestral haplotypes in patients with Mal de Meleda. J Invest Dermatol. 2003;120:351-55.

Bouadjar B, et al. Clinical and genetic studies of 3 large, consanguineous, Algerian families with Mal de Meleda. Arch Dermatol. 2000;136:1247-52.

Ayman, et al. Mal de Meleda: a review of Turkish patients. J Dermatol. 2000;27:664-68.

Fishcer J, et al. Genetic linkage of Meleda disease to chromosome 8qter. Eur J Hum Genet. 1998;6:542-47.

Salamon T. Hairgrowth over the thenar and the sole in Mal de Meleda (Mljet disease). Acta Derm Venereol. 1985;65:352-53.

Salamon T, et al. Electric microscopic study of fingernails in the disease of Mljet (Mal de Meleda). Acta Derm Venereol. 1984;64:302-07.

Salamon T. Nail changes in Meleda disease. Z Hautkr. 1982;57:1496-504.

Salamon T. Meleda disease - akroerythrokeratoderma. Z Hautkr. 1982;57:580-86.

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 248300; Last Update:1/9/2003.

Report last updated: 2008/03/08 00:00:00 GMT+0