- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. (PMID:15044640)
- Paraseptal emphysema (HP:0033649): Paraseptal emphysema is characterized by predominant involvement of the distal alveoli and their ducts and sacs. It is characteristically bounded by any pleural surface and the interlobular septa. This emphysema is characterized by subpleural and peribronchovascular regions of low attenuation separated by intact interlobular septa, sometimes associated with bullae. Evidence: PCS. Frequency: 2/11. (PMID:27516224)
- Bronchial wall thickening (HP:0033542): Radiological appearance of increased density around the walls of a bronchus or large bronchiole. This feature is thought to be related to edema involving the bronchial wall as well as the peribronchial interstitial space. If the cross section of a bronchus is captured in a radiograph or computed tomography image, it is said to have the appearance of a donut because of the central lucency representing the airway of the bronchus surrounded by a circular region of increased density. Evidence: PCS. Frequency: 7/11. (PMID:27516224)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: IEA. (OMIM:610921)
- Absent bronchoalveolar surfactant-protein C (HP:0032980): Significantly decreased level or failed detection of surfactant protein C in broncho-alveolar lavage fluid. Comment: Pulmonary surfactant is a highly surface-active mixture of proteins and lipids that is synthesized and secreted onto the alveoli by type II epithelial cells. The protein part of surfactant constitutes of four types of surfactant proteins (SP), SP-A, SP-B, SP-C and SP-D. SP-A and SP-D are hydrophilic proteins that regulate surfactant metabolism and have immunologic functions, whereas SP-B and SP-C are hydrophobic molecules, which play a direct role in the organization of the surfactant structure in the interphase and in the stabilization of the lipid layers during the respiratory cycle. Lack of SP-C may result of surfactant metabolism dysfunction and is also observed in patients with other diffuse parenchymal lung diseases, pathogenetically related to the alveolar surfactant region. Evidence: PCS. (PMID:27516224)
- Respiratory failure (HP:0002878): A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits. Evidence: PCS. Onset: Neonatal onset (HP:0003623). (PMID:15044640)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 2/21. (PMID:15044640)
- Exertional dyspnea (HP:0002875): Perceived difficulty to breathe that occurs with exercise or exertion and improves with rest. Evidence: PCS. (PMID:27516224)
- Desquamative interstitial pneumonitis (HP:0005942): Diffuse filling of the distal airspaces of the lungs, the alveoli, with macrophages. Desquamative interstitial pneumonitis (DIP) is characterized additionally by thickened alveolar septa and by a sparse inflammatory infiltrate that often includes plasma cells and occasional eosinophils. The alveoli are lined by plump cuboidal pneumocytes. Lymphoid aggregates may be present. Evidence: PCS. Frequency: 4/9. (PMID:15044640)
- Honeycomb lung (HP:0025175): Honeycombing represents destroyed and fibrotic lung tissue containing numerous cystic airspaces with thick fibrous walls, representing the late stage of various lung diseases, with complete loss of acinar architecture. The cysts range in size from a few millimeters to several centimeters in diameter, have variable wall thickness, and are lined by metaplastic bronchiolar epithelium. On chest radiographs, honeycombing appears as closely approximated ring shadows, typically 3-10 mm in diameter with walls 1-3 mm in thickness, that resemble a honeycomb; the finding implies end-stage lung disease. On CT scans, the appearance is of clustered cystic air spaces, typically of comparable diameters on the order of 3-10 mm but occasionally as large as 2.5 cm. Honeycombing is usually subpleural and is characterized by well-defined walls. It is a CT feature of established pulmonary fibrosis. Because honeycombing is often considered specific for pulmonary fibrosis and is an important criterion in the diagnosis of usual interstitial pneumonia, the term should be used with care, as it may directly impact patient care. Evidence: PCS. Frequency: 4/11. (PMID:27516224)
- Intraalveolar phospholipid accumulation (HP:0006517): Accumulation of amorphous PAS-positive material in the space between alveolar macrophages, sometimes as condensed form (oval bodies) are typically found in alveolar proteinosis. Evidence: PCS. Frequency: 18/19. (PMID:15044640;OMIM:610921)
- Cystic pattern on pulmonary HRCT (HP:0025394): On pulmonary high-resolution computed tomography, the cystic pattern is composed by well-defined, round and circumscribed air-containing parenchymal spaces with a well-defined wall and interface with normal lung. The wall of the cysts may be uniform or varied in thickness, but usually is thin (less than 2 mm) and occurs without associated emphysema. Evidence: PCS. Frequency: 8/11. (PMID:27516224)
- Respiratory distress (HP:0002098): Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea. Evidence: PCS. (PMID:15044640)
- Ground-glass opacification (HP:0025179): On chest radiographs, ground-glass opacity appears as an area of hazy increased lung opacity, usually extensive, within which margins of pulmonary vessels may be indistinct. On CT scans, it appears as hazy increased opacity of lung, with preservation of bronchial and vascular margins. It is caused by partial filling of airspaces, interstitial thickening (due to fluid, cells, and/or fibrosis), partial collapse of alveoli, increased capillary blood volume, or a combination of these, the common factor being the partial displacement of air. Ground-glass opacity is less opaque than consolidation, in which bronchovascular margins are obscured. Evidence: PCS. Frequency: 11/11. (PMID:27516224)
- Dyspnea (HP:0002094): Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale. Evidence: PCS. (PMID:27516224)
- Cough (HP:0012735): A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. Evidence: PCS. (PMID:27516224)
- Hypoxemia (HP:0012418): An abnormally low level of blood oxygen. Evidence: PCS. (PMID:27516224)
- Usual interstitial pneumonia (HP:0031950): Temporal and spatial heterogeneity in lungs based on presence of fibrosis and honeycombing. Evidence: PCS. Frequency: 1/23. (PMID:27516224)
- Nodular pattern on pulmonary HRCT (HP:0025392): A nodular pattern is characterized on pulmonary high-resolution computed tomography by the presence of numerous rounded opacities that range from 2 mm to 1 cm in diameter, with micronodules defined as smaller than 3 mm in diameter. Evidence: PCS. Frequency: 1/11. (PMID:27516224)
- Crazy paving pattern (HP:0025391): The so-called crazy paving pattern appears as thickened interlobular septa and intralobular lines superimposed on a background of ground-glass opacity, resembling irregularly shaped paving stones. The crazy-paving pattern is often sharply demarcated from more normal lung and may have a geographic outline. It was originally reported in patients with alveolar proteinosis and is also encountered in other diffuse lung diseases that affect both the interstitial and airspace compartments, such as lipoid pneumonia. Evidence: PCS. Frequency: 2/11. (PMID:27516224)
- Reticular pattern on pulmonary HRCT (HP:0025390): On pulmonary high-resolution computed tomography, reticular pattern is characterized by innumerable interlacing shadows suggesting a mesh. Evidence: PCS. Frequency: 11/11. (PMID:27516224)
- Nonspecific interstitial pneumonia (HP:0033584): Temporally uniform (all lesions are in the same stage of evolution) pattern of diffuse inflammatory interstitial process, mostly symmetric over the entire lung, involving mainly the alveolar septa. Evidence: PCS. Frequency: 7/23. (PMID:27516224)
- Autosomal recessive inheritance (HP:0000007): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:15044640)
- Clubbing (HP:0001217): Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails. Evidence: PCS. (PMID:27516224)
- Cyanosis (HP:0000961): Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood. Evidence: PCS. (PMID:27516224)
- Neonatal death (HP:0003811): Death within the first 28 days of life. Evidence: PCS. Frequency: 11/21. (PMID:15044640)
- Pulmonary fibrosis (HP:0002206): Replacement of normal lung tissues by fibroblasts and collagen. Evidence: PCS. Frequency: 2/23. (PMID:27516224)
- Tachypnea (HP:0002789): Very rapid breathing. Evidence: IEA. (OMIM:610921)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: IEA. (OMIM:610921)
- Neonatal respiratory distress (HP:0002643): Respiratory difficulty as newborn. Evidence: PCS. Frequency: 30/37. Onset: Neonatal onset (HP:0003623). (PMID:27516224)
These phenotypes are associated with the disease interstitial lung disease due to ABCA3 deficiency (OMIM:610921).