| Cohort/model | Age at onset / stage | Key phenotypes | Imaging / pathology | Biochemical findings | Genetic variant / genotype | Rarity / notes |
|---|---|---|---|---|---|---|
| Human case 1: first reported saposin A deficiency presenting as Krabbe disease | Infantile onset; exact onset not available in retrieved context | Krabbe-like / globoid cell leukodystrophy phenotype in an infant (pqac-00000007) | Not available in retrieved context | Saposin A deficiency reported as cause of Krabbe phenotype; detailed GALC/psychosine values not available in retrieved context (pqac-00000007) | Mutation in saposin A coding region of **PSAP**; exact HGVS not available in retrieved context (pqac-00000003, pqac-00000007) | First human report; establishes that saposin A deficiency can phenocopy Krabbe disease (pqac-00000003, pqac-00000007) |
| Human case 2: JIMD Reports 2018 proband | Normal early infancy, then deterioration by 7 months; infantile presentation (pqac-00000004) | Refractory seizures, loss of milestones/head control, feeding difficulty, hypertonicity, increased deep tendon reflexes, severe axonal polyneuropathy, elevated CSF protein 135 mg/dL; phenotype highly compatible with infantile Krabbe disease (pqac-00000004) | Brain MRI: bilateral ventricular enlargement, periventricular/centrum semiovale white matter hyperintensities, optic nerve thickening; MRI compatible with Krabbe disease (pqac-00000004, pqac-00000015) | GALC activity low in dried blood and reduced in leukocytes, but higher than expected for classic Krabbe; other lysosomal enzymes normal. Fibroblasts: GalCer 3.5-fold, LacCer 1.5-fold, Cer 2-fold, GlcCer 1.4-fold vs controls; increased LAMP1-positive lysosomes. Psychosine could not be assessed because only fibroblasts were available (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000015) | **PSAP** NM_002778.3:c.209T>G (p.Val70Gly), homozygous, in saposin A domain; GALC gene negative (pqac-00000000, pqac-00000004, pqac-00000015) | Second known human case; authors emphasize extreme rarity and recommend considering PSAP when Krabbe phenotype is present but GALC testing is inconclusive (pqac-00000000, pqac-00000005) |
| Mouse model: saposin A domain mutant / saposin A-deficient (C106F; often denoted SAP-A−/− or A−/−) | Subtle weakness/sluggishness around 60 days to 2.5 months; hind-leg atrophy/paralysis and weight plateau by ~3 months (pqac-00000022, pqac-00000023) | Chronic, milder Krabbe-like disease with progressive neuromotor decline; occasional seizures/hyperactivity (pqac-00000021, pqac-00000023) | Demyelination in CNS and PNS; PAS-positive multinucleated macrophages / globoid-like cells around vessels; enlarged peripheral nerves; pathology detectable by ~30 days in some studies (pqac-00000021, pqac-00000024, pqac-00000025, pqac-00000027) | Brain GALC activity ~0.74 ± 0.15 vs 1.41 ± 0.23 nmol/h/mg in wild type; slight brain GalCer increase, marked kidney GalCer increase; brain psychosine ~2–3× normal / approximately doubled by 2 months (pqac-00000020, pqac-00000021, pqac-00000025) | Targeted **Psap** saposin A-domain C106F mutation disrupting conserved disulfide bond (pqac-00000006, pqac-00000021, pqac-00000023) | Demonstrates saposin A is indispensable for in vivo GALC-mediated GalCer degradation and that saposin A deficiency is an alternative cause of globoid cell leukodystrophy (pqac-00000022, pqac-00000024) |
| Mouse comparator: twitcher (classic GALC-deficient Krabbe model) | Earlier onset than saposin A-deficient mice; terminal stage around PND 50 in comparative pathology studies (pqac-00000027) | Severe, rapidly progressive Krabbe phenotype (pqac-00000024, pqac-00000027) | More severe demyelination and globoid cell pathology than saposin A-deficient mice at earlier ages (pqac-00000024, pqac-00000027) | Much greater psychosine accumulation than saposin A-deficient mice; terminal twitcher mice show markedly elevated psychosine, with saposin A-deficient mice having only modest increases (pqac-00000021, pqac-00000025) | **Galc**-deficient twitcher genotype (pqac-00000024, pqac-00000027) | Benchmark canonical Krabbe model used to show saposin A deficiency causes a milder, later-onset but mechanistically related leukodystrophy (pqac-00000020, pqac-00000024, pqac-00000027) |
| Mouse comparator: saposin A-deficient vs twitcher lifespan | SAP-A−/− mean survival ~122 ± 17 days vs twitcher ~48 ± 5 days (pqac-00000020) | SAP-A−/− chronic course vs twitcher fulminant course (pqac-00000020, pqac-00000024) | SAP-A−/− terminal-stage pathology compared at PND 180 vs twitcher at PND 50 (pqac-00000027) | SAP-A−/− retains partial GALC-related function / compensation, whereas twitcher lacks primary GALC activity (pqac-00000020, pqac-00000022) | Comparative model evidence rather than a separate genotype row (pqac-00000020, pqac-00000027) | Useful for interpreting why human saposin A deficiency may show Krabbe phenotype despite noncanonical GALC findings (pqac-00000000, pqac-00000020) |


*Table: This table summarizes the reported human saposin A deficiency cases with Krabbe-like presentation and the main saposin A animal models used to define disease mechanism. It is useful for comparing clinical rarity, diagnostic findings, and the mechanistic contrast between PSAP/saposin A deficiency and classic GALC-deficient Krabbe disease.*