| Phenotype/feature | HPO term suggestion | Typical onset/course | Notes/frequency (if available) | Key evidence |
|---|---|---|---|---|
| Hepatosplenomegaly | HP:0001433 Hepatosplenomegaly | Infantile to childhood; progressive or persistent | Commonly reported visceral feature across cases/families | Seen in classic case summaries and recent reports; 4-month-old PSAP case had hepatosplenomegaly; also reported in Pakistani family and Indian infant (pqac-00000010, pqac-00000027, pqac-00000028, pqac-00000024) |
| Anemia | HP:0001903 Anemia | Infantile/childhood; chronic | Reported in Gaucher-like visceral presentations; not quantified for all cases | Listed among typical GD-like findings in SapC deficiency; present in Indian/Chinese summaries (pqac-00000010, pqac-00000024) |
| Thrombocytopenia | HP:0001873 Thrombocytopenia | Infantile to childhood; chronic | Recurrent hematologic finding | Reported in Pakistani family and in general SapC-deficiency phenotype descriptions (pqac-00000010, pqac-00000028, pqac-00000024) |
| Bone lesions / kyphosis | HP:0002650 Scoliosis/Kyphosis; HP:0002758 Osteolysis or HP:0000930 Generalized osteopenia | Childhood to adult; progressive/variable | Bone lesions are part of GD-like spectrum; kyphosis specifically reported in Pakistani family | Bone disease noted in reviews; kyphosis reported with p.Glu359Ala family (pqac-00000010, pqac-00000028) |
| Pulmonary hypertension | HP:0002092 Pulmonary hypertension | Variable; likely later complication | Mentioned as part of GD clinical spectrum in SapC-deficiency review, not clearly frequency-defined for SapC cases | Listed among clinical features in 2014 mechanistic paper introduction (pqac-00000013) |
| Seizures / encephalopathy | HP:0001250 Seizure; HP:0001298 Encephalopathy | Early infantile in severe neuronopathic cases; can be rapidly progressive | Indian infant had encephalopathy and refractory seizures; severe neonatal/infantile presentations reported | 2-month-old infant with encephalopathy and resistant tonic-clonic seizures died by 4 months (pqac-00000024) |
| Hypotonia | HP:0001252 Hypotonia | Early infantile; progressive in severe cases | Present in severe infantile case; also 4-month-old PSAP_PT had hypotonia | Reported in Indian infant and PSAP_PT with severe neurologic disease (pqac-00000024, pqac-00000027) |
| Nystagmus | HP:0000639 Nystagmus | Early infantile in severe neuronopathic case | Reported in PSAP_PT suspected as GD2-like | 4-month-old infant had hypotonia, nystagmus, swallowing difficulty (pqac-00000027) |
| Ataxia | HP:0001251 Ataxia | Childhood to adult; progressive neurologic course | Seen in type 3-like / neuronopathic presentations and mouse models | Included in human clinical spectrum and supported by SapC-deficient mouse phenotype (pqac-00000010, pqac-00000020) |
| Myoclonic epilepsy | HP:0001336 Myoclonic seizures | Childhood/adolescent; progressive neuronopathic course | Reported in GD-like neurologic spectrum due to SapC deficiency | Included in SapC-deficiency clinical overlap with type 3 GD (pqac-00000010) |
| Abnormal horizontal saccades | HP:0000640 Oculomotor apraxia / HP:0000616 Abnormality of eye movement | Childhood/adolescent; neurologic | Characteristic neuronopathic GD-like feature in some reported cases | Listed in review of six reported patients (pqac-00000010) |
| Hearing impairment | HP:0000365 Hearing impairment | Congenital/prelingual or childhood; non-progressive/progressive uncertain | All affected members in Pakistani family had hearing impairment; prelingual profound SNHL highlighted | Strong feature in p.Glu359Ala family (pqac-00000002, pqac-00000028) |
| Vestibular dysfunction | HP:0001751 Vestibular areflexia / HP:0001756 Vestibular dysfunction | Childhood; chronic | Reported with hearing impairment in Pakistani family | Present in all affected family members in phenotype-expansion report (pqac-00000002, pqac-00000028) |
| GCase activity may be normal in vitro | HP:0012378 Abnormal enzyme/coenzyme activity | Diagnostic caveat; may obscure diagnosis | Important distinguishing feature: SapC deficiency can present despite normal standard GCase assay results | Human SapC-deficient cases can show normal in vitro GCase activity; one case had normal skin fibroblast GCase despite biomarker abnormalities (pqac-00000010, pqac-00000011, pqac-00000008, pqac-00000026) |
| Tissue glucosylceramide accumulation | HP:0011015 Abnormal sphingolipid concentration | Persistent biochemical hallmark | May be demonstrated in spleen/tissue despite normal enzyme assay | Spleen glucosylceramide accumulation documented in variant Gaucher due to SapC deficiency (pqac-00000011) |
| Plasma chitotriosidase elevation | HP:0034046 Increased circulating chitotriosidase level | Elevated at diagnosis; reflects macrophage activation | Markedly elevated in severe infantile PSAP case | PSAP_PT chitotriosidase 2951.0 nmol/mL/h (pqac-00000009, pqac-00000027) |
| Plasma glucosylsphingosine (GlcSph) elevation | HP:0034383 Increased circulating glucosylsphingosine | Elevated at diagnosis | Useful GD biomarker in PSAP-related GCase deficiency | PSAP_PT plasma GlcSph 19.0 ng/mL (pqac-00000009, pqac-00000027) |
| Lyso-Gb3 elevation | HP:0034380 Abnormal globotriaosylsphingosine level | Elevated at diagnosis in reported case | Ancillary lipid biomarker; may assist broader sphingolipid profiling | PSAP_PT Lyso-Gb3 1.98 ng/mL (pqac-00000009, pqac-00000027) |
| PPCS elevation | HP:0034385 Abnormal lysosphingolipid profile | Elevated at diagnosis in reported case | Additional plasma biomarker reported in 2024 study | PSAP_PT PPCS 745.9 ng/mL (pqac-00000009, pqac-00000027) |
| Genetic testing for PSAP variants | HP:0000007 Autosomal recessive inheritance | Confirmatory test; indicated when GD suspected but GBA1 negative or biochemistry atypical | Reported pathogenic variant classes include missense, nonsense, splice-site, start-loss, and deletions | PSAP sequencing/WES/Sanger used across cases; variants include p.E297*, p.Glu359Ala, p.C382G/F, p.L349P, c.1005+1G>A (pqac-00000002, pqac-00000013, pqac-00000027) |
| Negative GBA1 testing should trigger PSAP evaluation | HP:0000007 Autosomal recessive inheritance | Diagnostic workflow recommendation | Particularly important in infantile GD-like disease with elevated biomarkers and low-normal/normal GCase assays | 2024 PSAP_PT was GBA1-negative then diagnosed by PSAP testing; Indian report explicitly advises considering specific activator deficiency when GD is suspected with partially deficient or near-normal GBA activity (pqac-00000027, pqac-00000024) |


*Table: This table summarizes the reported clinical spectrum and key diagnostic findings for Gaucher disease due to saposin C deficiency caused by PSAP variants. It is useful for distinguishing this ultra-rare activator deficiency from canonical GBA1-related Gaucher disease, especially when enzyme activity is normal or only mildly reduced.*