- Middle age onset (HP:0003596, a Human Phenotype Ontology term): A type of adult onset with onset of symptoms at the age of 40 to 60 years. Evidence: PCS. Frequency: 5/15. (PMID:22818240)
- Decreased circulating HDL-C concentration (HP:0003233, a Human Phenotype Ontology term): The concentration of high-density lipoprotein cholesterol in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 36/44. (PMID:15545621;PMID:22818240)
- Short stature (HP:0004322, a Human Phenotype Ontology term): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: IEA. (OMIM:607616)
- Hepatomegaly (HP:0002240, a Human Phenotype Ontology term): Abnormally increased size of the liver. Evidence: PCS. Frequency: 10/15. (PMID:22818240)
- Decreased DLCO (HP:0045051, a Human Phenotype Ontology term): Reduced ability of the lungs to transfer gas from inspired air to the bloodstream as measured by the diffusing capacity of the lungs for carbon monoxide (DLCO) test. Evidence: PCS. Frequency: 5/8. (PMID:22818240)
- Childhood onset (HP:0011463, a Human Phenotype Ontology term): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/15. (PMID:22818240)
- Anemia (HP:0001903, a Human Phenotype Ontology term): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 4/15. (PMID:22818240)
- Young adult onset (HP:0011462, a Human Phenotype Ontology term): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 7/15. (PMID:22818240)
- Decreased acid sphingomyelinase activity (HP:0034300, a Human Phenotype Ontology term): Reduced activity of the enzyme acid sphingomyelinase activity in the blood circulation. Evidence: TAS. (OMIM:607616)
- Foam cells with lamellar inclusion bodies (HP:0003609, a Human Phenotype Ontology term): The presence of foam cells that contain lamellar inclusion bodies. Evidence: IEA. (OMIM:607616)
- Abnormal pulmonary interstitial morphology (HP:0006530, a Human Phenotype Ontology term): Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis. Evidence: PCS. Frequency: 2/15. (PMID:22818240)
- Abnormal macular morphology (HP:0001103, a Human Phenotype Ontology term): A structural abnormality of the macula, a region that, in a clinical context, is typically used to describe the central part of the retina within the vascular arcades. Evidence: IEA. (OMIM:607616)
- Mental deterioration (HP:0001268, a Human Phenotype Ontology term): Loss of previously present mental abilities, generally in adults. Evidence: PCS. Frequency: 0/15. (PMID:22818240)
- Splenomegaly (HP:0001744, a Human Phenotype Ontology term): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 14/15. (PMID:22818240)
- Juvenile onset (HP:0003621, a Human Phenotype Ontology term): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 2/15. (PMID:22818240)
- Sea-blue histiocytosis (HP:0001982, a Human Phenotype Ontology term): An abnormality of histiocytes, in which the cells take on a sea blue appearance due to abnormally increased lipid content. Histiocytes are a type of macrophage. Sea-blue histiocytes are typically large macrophages from 20 to 60 micrometers in diameter with a single eccentric nucleus whose cytoplasm if packed with sea-blue or blue-green granules when stained with Wright-Giemsa. Evidence: IEA. (OMIM:607616)
- Hypertriglyceridemia (HP:0002155, a Human Phenotype Ontology term): An abnormal increase in the level of triglycerides in the blood. Evidence: PCS. Frequency: 24/29. (PMID:22818240)
- Bone-marrow foam cells (HP:0004333, a Human Phenotype Ontology term): The presence of foam cells in the bone marrow, generally demonstrated by bone-marrow aspiration or biopsy. Foam cells have a vacuolated appearance due to the presence of complex lipid deposits, giving them a foamy or soap-suds appearance. Evidence: IEA. (OMIM:607616)
- Elevated circulating LDL-C concentration (HP:0003141, a Human Phenotype Ontology term): The concentration of low-density lipoprotein cholesterol in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 23/44. (PMID:15545621;PMID:22818240)
- Dyspnea (HP:0002094, a Human Phenotype Ontology term): Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale. Evidence: IEA. (OMIM:607616)
- Arthralgia (HP:0002829, a Human Phenotype Ontology term): Joint pain. Evidence: PCS. Frequency: 2/15. (PMID:22818240)
- Autosomal recessive inheritance (HP:0000007, a Human Phenotype Ontology term): 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: IEA. (OMIM:607616)
- Diffuse reticular or finely nodular infiltrations (HP:0002207, a Human Phenotype Ontology term). Evidence: IEA. (OMIM:607616)
- Recurrent respiratory infections (HP:0002205, a Human Phenotype Ontology term): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: IEA. (OMIM:607616)
- Thrombocytopenia (HP:0001873, a Human Phenotype Ontology term): A reduction in the number of circulating thrombocytes. Evidence: PCS. Frequency: 8/15. (PMID:22818240)
- Elevated circulating lysosphingomyelin concentration (HP:6001380, a Human Phenotype Ontology term): The concentration of lysosphingomyelin in the blood circulation is above the upper limit of normal. Acid sphingomyelinase deficiency (ASMD) or Niemann-Pick type A/B is a lysosomal disorder caused by the deficiency of acid sphingomyelinase (ASM) due to pathogenic variants in the SMPD1 gene. Sphingomyelin (SM) is the substrate for ASM that cleaves the phosphorylcholine linkage of SM producing ceramide. SM is a major compound of most cell membranes and coupled with cholesterol constitutes most of the membrane rafts. In the deficiency of ASM, there is primary storage of SM, and the concentration of lysosphingomyelin in dried blood spots and in the blood circulation is typically elevated. Evidence: PCS. (PMID:36348386)
These phenotypes are associated with the disease Niemann-Pick disease type B (OMIM:607616, an entry in Online Mendelian Inheritance in Man).