Alveolar Capillary Dysplasia

Alveolar Capillary Dysplasia

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Alveolar Capillary Dysplasia is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • ACD

Disorder Subdivisions

  • None

General Discussion

Alveolar capillary dysplasia (ACD) is a rare, likely congenital, disorder of the lungs (pulmonary system) and especially of the blood system serving the lungs. It is a disorder of the newborn. The normal diffusion process of oxygen from the air sacs to the blood in the lungs and, thence, to the heart, fails to develop properly. The disorder is sometimes called misalignment of the pulmonary veins. Rather than misaligned, the pulmonary vein is malpositioned in a site somewhat different from its normal position.



Infants with the disorder present with the signs of lack of oxygen (hypoxemia) and severely increased pulmonary hypertension.



Since treatment is seldom, if ever, effective, life expectancy of the infant is very, very, short.

Symptoms

Infants, most often in the first few days of life, present with the signs of a lack of oxygen (cyanosis) and high blood pressure in the pulmonary artery (neonatal pulmonary hypertension). Many patients will also show signs of cardiac anomalies, and/or systemic abnormalities of the urinary or gastrointestinal tract.



The disorder is noted for its superficial resemblance to idiopathic persistent pulmonary hypertension of the newborn (PPHN) with which ACD may be confused. In contrast to infants with PPHN, those with ACD do not respond to heroic efforts such as mechanical ventilation, nitric oxide, and extra corporeal membrane oxygenation (ECMO). ECMO is a special procedure that uses an artificial heart-lung machine to take over the work of the lungs (and sometimes also the heart). This procedure is used most often in newborns and young children, but it also can be used as a last resort for adults whose heart or lungs are failing.



ACD may be accompanied by other systemic symptoms, such as disorders of the eye and heart, and may even mimic the genetic disorder trisomy 21.

Causes

For reasons that are unclear, the capillaries and small veins of the emerging lungs fail to develop properly before birth. While in the womb, immature veins (venous channels) arise located, inappropriately, in what is called the bronchovascular bundle. These immature veins attach themselves to the pulmonary veins that are in their typical locations. This is the origin of the idea of misaligned pulmonary veins. This process was made clear by studies of the cells of the lungs (histological) of very young or premature infants.



The cause(s) of ACD is (are) not known although at least one-half a dozen cases among family members (siblings) have been reported. Based on these observations, and other evidence, some clinicians believe that there may be a genetic component to ACD that is not fully understood. Despite intensive searching, the faulty gene has not been identified and thus the location of this faulty gene remains unknown. Clinicians believe that the genetic trait involved is most likely transmitted as an autosomal recessive trait.



Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. 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 11p13" refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.



Genetic diseases are determined by the combination of genes for a particular trait that are located on the chromosomes received from the father and 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%. The risk is the same for males and females.



All individuals carry 4-5 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.

Affected Populations

As of 1997, there were about 50 cases of alveolar capillary dysplasia reported. There are certainly many more now. The disorder appears to affect infants born at full term, and affects girls and boys equally.

Standard Therapies

Diagnosis

Alveolar capillary dysplasia may be suspected in any infant who presents with severe cyanosis (hypoxemia) and high pulmonary blood pressure (pulmonary hypertension) that is unresponsive to treatment in the neonatal intensive care unit (NICU). The diagnosis is confirmed through an examination of lung tissue by an experienced pathologist for characteristic cellular changes. The characteristics that a pathologist will look for include, according to one expert, a relative lack of capillaries near the alveoli, thickening of the walls (septa) of alveoli, and increased "muscularization" of the small arteries of the lungs (arterioles).



Treatment

None of the many treatment modes that are used to treat pulmonary hypertension have resulted in prolonging life expectancy or long-term survival. The methods tried include mechanical ventilation, inhaling high concentrations of oxygen, inhaled nitric oxide, and ECMO (extracorporeal membrane oxygenation).

Investigational Therapies

A number of clinical trials involving inhaled nitric oxide have proven effective for the treatment of neonatal pulmonary disorders such as idiopathic persistent pulmonary hypertension. None have been effective in treating ACD. There has been talk about trying lung transplantation but progress in this direction has been held up because of the scarcity of donor lung tissue.



Investigators at the Baylor College of Medicine, working with the support of the Alveolar Capillary Dysplasia Association, are engaged in efforts to identify the faulty gene responsible for ACD.



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

References

TEXTBOOKS

Steinhorn RH. Alveolar Capillary Dysplasia. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:672.



JOURNAL ARTICLES

Barresi V, Grosso M, Vitarelli E, Granese R, Barresi G. Endoglin (CD105) immuno-expression in human fetal and neonatal lungs. Histol Histopathol. 2008 Jun;23(6):701-8.



Thebaud B. Angiogenesis in lung development, injury and repair: implications for chronic lung disease of prematurity. Neonatology. 2007;91(4):291-7. Epub 2007 Jun 7.



Pucci A, Zanini C, Ferrero F, et al. Misalignment of lung vessels: diagnostic role of conventional histology and immunohistochemistry. Virchows Arch. 2003;442:597-600.



Coalson JJ. Pathology of new bronchopulmonary dysplasia. Semin Neonatol. 2003;8:73-81.

Hislop AA. Airway and blood vessel interaction during lung development. J Anat. 2002;201:325-34.



Cassidy J, Smith J, Goldman A, et al. The incidence and characteristics of neonatal irreversible lung dysplasia. J Pediatr. 2002;141:426-28.



Tibbals J, Chow CW. Incidence of alveolar capillary dysplasia in severe idiopathic persistent pulmonary hypertension of the newborn. J Paediatr Child Health. 2002;38:397-400.



Alameh J, Bachiri A, Devisme L, et al. Alveolar capillary dysplasia: a cause of persistent pulmonary hypertension of the newborn. Eur J Pediatr. 2002;161:262-66.



Merchak A, Lueder GT, White FV, et al. Alveolar capillary dysplasia with misalignment of pulmonary veins and anterior segment dysgenesis of the eye: a report of a new association and review of the literature. J Perinatol. 2001;21:327-30.



McGaughran J, Souter DJ, Kuschel CA. Alveolar capillary dysplasia with antenatal anomalies mimicking trisomy 21. J Paediatr Child Health. 2001;37:85-86.



Rabah R, Poulik JM. Congenital alveolar capillary dysplasia with misalignment of pulmonary veins associated with hypoplastic left heart syndrome. Pediatr Dev Pathol. 2001;4:167-74.



Al-Hathlol K, Phillips S, Seshia MK, et al. Alveolar capillary dysplasia. Report of a case of prolonged life without extracorporeal membrane oxygenation (ECMO) and review of the literature. Early Hum Dev. 2000;57:85-94.



Somaschini M, Bellan C, Chinaglia D, et al. Congenital misalignment of pulmonary vessels alveolar capillary dysplasia: how to manage a neonatal irreversible lung disease? J Perinatol. 2000;20:189-92.



Hintz SR, Vincent JA, Pitlick PT, et al. Alveolar capillary dysplasia: diagnostic potential for cardiac catheterization. J Perinatol. 1999;

19(6 Pt 1)441046.



FROM THE INTERNET

Steinhorn RH. Pulmonary Hypertension, Persistent-Newborn. eMedicine Journal. Last Updated: June 9, 2003. 17pp.

www.emedicine.com/ped/topic2530.htm



Natarajan G, Abdulhamid I. emedicine. Last Updated: April 6, 2003. 17pp.

www.emedicine.com/ped/topic2627.htm



Suchomski SJ. Persistent Pulmonary Hypertension of the Newborn. December 2001. 9pp.

www.dcmsonline.org/jax-medicine/2001journals/dec2001/hypertension.htm



Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Date edited: 8/22/2001. 31pp.

www.nichd.nih.gov/cochrane/finer/finer.htm



Barrington KJ, Finer NN. Inhaled nitric oxide for respiratory failure in preterm infants. Date edited: 8/16/2001. 18pp.

www.nichd.nih.gov/cochrane/barrington/barring1.htm

Resources

American Lung Association

1301 Pennsylvania Ave NW

Suite 800

Washington, DC 20004

USA

Tel: (202)785-3355

Fax: (202)452-1805

Tel: (800)586-4872

Email: info@lungusa.org

Internet: http://www.lungusa.org



Alveolar Capillary Dysplasia Association

c/o Steve and Donna Hanson

5902 Marcie Court

Garland, TX 75044-4958

Email: sdesj@verizon.net

Internet: http://www.acd-association.com



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Infants Remembered In Silence, Inc. (IRIS)

112 Third Street NE

Faribault, MN 55021

Tel: (507)334-4748

Fax: (507)334-4748

Email: support@irisremembers.com

Internet: http://www.irisRemembers.com



Fetal Hope Foundation

9786 South Holland Street

Littleton, CO 80127

USA

Tel: (303)932-0553

Tel: (877)789-4673

Email: info@fetalhope.org

Internet: http://www.fetalhope.org



Share Pregnancy & Infant Loss Support, Inc.

402 Jackson Street

Saint Charles, MO 63301

Tel: (636)947-6164

Fax: (636)947-7486

Tel: (800)821-6819

Email: info@nationalshare.org

Internet: http://www.nationalshare.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.