Failure to thrive, and Respiratory distress

Interstitial lung disease due to ABCA3 deficiency is a rare genetic respiratory disease characterized by a variable clinical outcome ranging from a fatal respiratory distress syndrome in the neonatal period to chronic interstitial lung disease developing in infancy or childhood with chronic cough, rapid breathing, shortness of breath and recurrent pulmonary infections. Clinical manifestations of respiratory failure include grunting, intercostal retractions, nasal flaring, cyanosis, and progressive dyspnea.

INTERSTITIAL LUNG DISEASE DUE TO ABCA3 DEFICIENCY Is also known as pulmonary alveolar proteinosis, congenital, 3|interstitial lung disease due to abca3 deficiency|interstitial lung disease due to atp-binding cassette subfamily a member 3 deficiency

• Failure to thrive
• Hypertension
• Respiratory distress
• Patent ductus arteriosus
• Respiratory failure

SOURCES: OMIM ORPHANET MENDELIAN

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. Three forms of PAP have been described: hereditary (usually congenital), secondary, and acquired. Hereditary PAP is associated with mutations in the CSF2RA gene or in genes encoding surfactant proteins. Secondary PAP develops in conditions in which there are reduced numbers or functional impairment of alveolar macrophages and is associated with inhalation of inorganic dust (silica) or toxic fumes, hematologic malignancies, pharmacologic immunosuppression, infections, and impaired CSF2RB (OMIM ) expression. Acquired PAP (OMIM ), the most common form, usually occurs in adults and is caused by neutralizing autoantibodies to CSF2 (OMIM ) (Martinez-Moczygemba et al., 2008).For a general phenotypic description and a discussion of genetic heterogeneity of congenital pulmonary surfactant metabolism dysfunction, see SMDP1 (OMIM ).

SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 4; SMDP4 Is also known as pulmonary alveolar proteinosis, congenital, 4|csf2ra deficiency|pap due to csf2ra deficiency

• Growth delay
• Failure to thrive
• Respiratory insufficiency
• Respiratory distress
• Pneumonia

SOURCES: MESH OMIM MENDELIAN

• Generalized hypotonia
• Growth delay
• Failure to thrive
• Feeding difficulties
• Hepatomegaly

SOURCES: OMIM MENDELIAN

Cardiomyopathy-hypotonia-lactic acidosis syndrome is characterised by hypertrophic cardiomyopathy, muscular hypotonia and the presence of lactic acidosis at birth. It has been described in two sisters (both of whom died within the first year of life) from a nonconsanguineous Turkish family. The syndrome is caused by a homozygous point mutation in the exon 3A of the SLC25A3 gene encoding a mitochondrial membrane transporter.

CARDIOMYOPATHY-HYPOTONIA-LACTIC ACIDOSIS SYNDROME Is also known as mpcd

• Generalized hypotonia
• Failure to thrive
• Muscular hypotonia
• Respiratory insufficiency
• Respiratory distress

SOURCES: ORPHANET MESH OMIM MENDELIAN

HIGM3, first described in humans by Ferrari et al. (2001), is characterized by hypogammaglobulinemia with normal or elevated levels of IgM.For a general phenotypic description and a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (OMIM ).

IMMUNODEFICIENCY WITH HYPER-IGM, TYPE 3; HIGM3 Is also known as hyper-igm syndrome 3

• Failure to thrive
• Hepatomegaly
• Respiratory distress
• Immunodeficiency
• Pneumonia

SOURCES: OMIM MENDELIAN

N-acetylglutamate synthase (NAGS) deficiency is a urea cycle disorder leading to hyperammonaemia.

HYPERAMMONEMIA DUE TO N-ACETYLGLUTAMATE SYNTHASE DEFICIENCY Is also known as hyperammonemia due to n-acetylglutamate synthetase deficiency|n-acetylglutamate synthetase deficiency|nags deficiency

• Seizures
• Global developmental delay
• Failure to thrive
• Cognitive impairment
• Feeding difficulties

SOURCES: MESH ORPHANET OMIM MENDELIAN

Surfactant protein C (SPC) deficiency is a rare autosomal dominant disease associated with progressive respiratory insufficiency and lung disease with a variable clinical course. The pathophysiology of the disorder is postulated to involve intracellular accumulation of a structurally defective SPC protein (Thomas et al., 2002).For a general phenotypic description and a discussion of genetic heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1 (OMIM ).

SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 2; SMDP2 Is also known as interstitial lung disease due to surfactant protein c deficiency|desquamative interstitial pneumonitis due to surfactant protein c deficiency|pulmonary alveolar proteinosis, congenital, 2

• Failure to thrive
• Pain
• Respiratory insufficiency
• Respiratory distress
• Recurrent infections

SOURCES: OMIM MENDELIAN

Inborn errors of pulmonary surfactant metabolism are genetically heterogeneous disorders resulting in severe respiratory insufficiency or failure in full-term neonates or infants. These disorders are associated with various pathologic entities, including pulmonary alveolar proteinosis (PAP), desquamative interstitial pneumonitis (DIP), or cellular nonspecific interstitial pneumonitis (NSIP) (Clark and Clark, 2005).A clinically similar disorder characterized by respiratory distress (OMIM ) can affect preterm infants, who show developmental deficiency of surfactant.Acquired PAP (OMIM ) is an autoimmune disorder characterized by the presence of autoantobodies to CSF2 (OMIM ). Genetic Heterogeneity of Pulmonary Surfactant Metabolism DysfunctionSee also SMDP2 (OMIM ), caused by mutation in the SPTPC gene (OMIM ) on 8p21; SMDP3 (OMIM ), caused by mutation in the ABCA3 gene (OMIM ) on 16p13; SMDP4 (OMIM ), caused by mutation in the CSF2RA gene (OMIM ) on Xp22; and SMDP5 (OMIM ), caused by mutation in the CSF2RB gene (OMIM ) on 22q12.

NEONATAL ACUTE RESPIRATORY DISTRESS DUE TO SP-B DEFICIENCY Is also known as neonatal acute respiratory distress due to surfactant protein b deficiency|pulmonary alveolar proteinosis, congenital, 1|interstitial lung disease due to surfactant protein b deficiency|interstitial lung disease, nonspecific, due to surfactant protein b d

• Failure to thrive
• Pain
• Hypertension
• Fever
• Fatigue

SOURCES: OMIM ORPHANET MESH MENDELIAN

Immunodeficiency-19 (IMD19) is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype. The disorder is lethal in early childhood without bone marrow transplantation (summary by Yu et al., 2011).

IMMUNODEFICIENCY 19; IMD19 Is also known as scid, t cell-negative, b cell-positive, nk cell-positive|cd3-delta deficiency|severe combined immunodeficiency, t cell-negative, b cell-positive, nk cell-positive

• Failure to thrive
• Fever
• Respiratory distress
• Diarrhea
• Immunodeficiency

SOURCES: OMIM MENDELIAN

Interstitial lung and liver disease is an autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood. Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis (summary by Hadchouel et al., 2015).

INTERSTITIAL LUNG AND LIVER DISEASE; ILLD Is also known as infantile liver failure syndrome 2, formerly|pulmonary alveolar proteinosis, reunion island|ilfs2, formerly

• Generalized hypotonia
• Failure to thrive
• Anemia
• Motor delay
• Hepatomegaly

SOURCES: OMIM MENDELIAN