- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 3/3. (PMID:16434659)
- Short stature (HP:0004322): 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:257200)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: PCS. (PMID:16434659)
- Rigidity (HP:0002063): Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Evidence: IEA. (OMIM:257200)
- Cherry red spot of the macula (HP:0010729): Pallor of the perifoveal macula of the retina with appearance of a small circular reddish choroid shape as seen through the fovea centralis due to relative transparency of the macula. Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Elevated circulating alanine aminotransferase concentration (HP:0031964): An abnormally high concentration in the circulation of alanine aminotransferase (ALT). Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: IEA. (OMIM:257200)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Foam cells with lamellar inclusion bodies (HP:0003609): The presence of foam cells that contain lamellar inclusion bodies. Evidence: IEA. (OMIM:257200)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: PCS. Frequency: 10/10. Onset: Infantile onset (HP:0003593). (PMID:16434659)
- Lymphadenopathy (HP:0002716): Enlargement (swelling) of a lymph node. Evidence: IEA. (OMIM:257200)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: IEA. (OMIM:257200)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: IEA. (OMIM:257200)
- Macrocephaly (HP:0000256): Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Evidence: PCS. Frequency: 2/10. (PMID:16434659)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: IEA. (OMIM:257200)
- Prolonged neonatal jaundice (HP:0006579): Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants. Evidence: PCS. Frequency: 1/10. (PMID:16434659)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: IEA. (OMIM:257200)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:257200)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Elevated circulating aspartate aminotransferase concentration (HP:0031956): The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Sea-blue histiocytosis (HP:0001982): 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:257200)
- Bone-marrow foam cells (HP:0004333): 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:257200)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: IEA. (OMIM:257200)
- Xanthomatosis (HP:0000991): The presence of multiple xanthomas (xanthomata) in the skin. Xanthomas are yellowish, firm, lipid-laden nodules in the skin. Evidence: TAS. (OMIM:257200)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- Ascites (HP:0001541): Accumulation of fluid in the peritoneal cavity (between the layers of the peritoneum that lines the abdomen). Evidence: PCS. Frequency: 2/10. (PMID:16434659)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: PCS. Frequency: 10/10. (PMID:16434659)
- 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: IEA. (OMIM:257200)
- Diffuse reticular or finely nodular infiltrations (HP:0002207). Evidence: IEA. (OMIM:257200)
- Microcytic anemia (HP:0001935): A kind of anemia in which the volume of the red blood cells is reduced. Evidence: IEA. (OMIM:257200)
- Protuberant abdomen (HP:0001538): A thrusting or bulging out of the abdomen. Evidence: IEA. (OMIM:257200)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: PCS. (PMID:16434659)
- Athetosis (HP:0002305): A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest. Evidence: IEA. (OMIM:257200)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: IEA. (OMIM:257200)
- Elevated circulating lysosphingomyelin concentration (HP:6001380): 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 A (OMIM:257200).