ABSTRACT
This is the first reported case of prosaposin ( PSAP ) mutation from India manifesting as an acute neuronal Gaucher disease-like condition. A 2-month-old male baby presented with encephalopathy, resistant tonic-clonic seizures, moderate hepatosplenomegaly, hypotonia, and cherry red spot in the retinae. The child had anemia, thrombocytopenia, elevated chitotriosidase, and normal activity of acid sphingomyelinase and low normal activity of ß-glucosidase 1 (ß-glucocerebrosidase 1, GBA). The child succumbed in the fourth month of life due to persistent respiratory distress and refractory seizures. The clinical phenotype, cherry red spots, elevated chitotriosidase, and lysosomal assays led to the suspicion of Gaucher disease. Exome sequencing revealed a homozygous stop codon mutation in the PSAP gene (c.G1228T, p.Glu410ter). Prenatal diagnosis in the next pregnancy revealed a carrier fetus, who was unaffected postnatally. The diagnosis of specific activator deficiency such as saposin C and saposin D deficiency (in the current study) should be considered and tested for when Gaucher disease is suspected in an infant with partially deficient or near normal GBA activity.
ABSTRACT
OBJECTIVE: Plasma chitotriosidase is a documented biomarker for certain lysosomal storage disorders. However, its clinical utility for prenatal samples is not elucidated yet. METHODS: We have established Reference intervals for amniotic fluid chitotriosidase using control amniotic fluids (nâ¯=â¯47) and compared the activity with amniotic fluids affected by lysosomal storage disorders (nâ¯=â¯25). RESULTS: The reference interval established was 0-6.76â¯nmol/h/ml. The amniotic fluids affected with LSDs exhibited elevation of chitotriosidase. The area under the curve (AUC) of receiver operating characteristic curve for affected vs. healthy was 0.987 indicating 98.6% accuracy of chitotriosidase in identifying pregnancies affected with LSDs. Among the different LSDs, Gaucher (202.00⯱â¯35.27â¯nmol/h/ml) and Niemann-pick A/B (60.33⯱â¯21.59â¯nmol/h/ml) showed very high levels of chitotriosidase. CONCLUSION: Amniotic fluid chitotriosidase has the potential to serve as a diagnostic marker for lysosomal storage disorders, more specifically for Gaucher and Niemann-Pick A/B.
Subject(s)
Amniocentesis , Amniotic Fluid/enzymology , Hexosaminidases/metabolism , Lysosomal Storage Diseases/diagnosis , Up-Regulation , Adult , Area Under Curve , Biomarkers/metabolism , Cells, Cultured , Cohort Studies , Exons , Female , Gaucher Disease/diagnosis , Gaucher Disease/enzymology , Gaucher Disease/genetics , Gaucher Disease/pathology , Gene Duplication , Hexosaminidases/chemistry , Hexosaminidases/genetics , Humans , India , Lysosomal Storage Diseases/enzymology , Lysosomal Storage Diseases/genetics , Lysosomal Storage Diseases/pathology , Mutation Rate , Niemann-Pick Disease, Type A/diagnosis , Niemann-Pick Disease, Type A/enzymology , Niemann-Pick Disease, Type A/genetics , Niemann-Pick Disease, Type A/pathology , Niemann-Pick Disease, Type B/diagnosis , Niemann-Pick Disease, Type B/enzymology , Niemann-Pick Disease, Type B/genetics , Niemann-Pick Disease, Type B/pathology , Pregnancy , Pregnancy Trimester, Second , ROC Curve , Reference Values , Young AdultABSTRACT
BACKGROUND: Lysinuric protein intolerance is an inherited disorder of transport of cationic amino acids, causing amino aciduria. CASE CHARACTERISTICS: A 3-year-old boy with 12 month history of episodic change in behavior (decreased sleep, poor interaction), stunted growth and hyperammonemia. OUTCOME: Genetic analysis revealed a homozygous mutation, c.158C>T (p.Ser53Leu) in exon 1 of SLC7A7 gene. With appropriate management of hyperammonemia episodes, his neurodevelopmental outcome is normal. MESSAGE: Lysinusic protein intolerance is a potentially treatable disorder and should not to be missed.
