| Study (first author, year) | Publication type | URL/DOI | Patient count / families | Inheritance / genotype | Key phenotypes | Key biochemical findings (urine 5-oxoproline values/units) | Key interpretation |
|---|---|---|---|---|---|---|---|
| Almaghlouth, 2012 | Human case report / family study | https://doi.org/10.1111/j.1399-0004.2011.01728.x | 2 homozygous siblings in 1 consanguineous family; paper notes only 8 patients from 6 families had been reported previously | Autosomal recessive; first molecularly confirmed human OPLAH defect: NM_017570.3:c.2601_2602insC, p.(His870Profs*92); parents heterozygous, sister homozygous | Variable spectrum in literature from apparently asymptomatic/developmentally normal to low IQ, delayed psychomotor development, microcephaly, failure to thrive, microcytic anemia, nephrolithiasis, enterocolitis, transient neonatal hypoglycemia; index case had mild indirect hyperbilirubinemia, mild metabolic acidosis, eczema/food allergies, slowed head growth but normal motor/social/cognitive development (pqac-00000000, pqac-00000004) | Markedly elevated urinary 5-oxoproline by GC-MS; index ratio 7.60 vs average control 0.06; homozygous sister 3.76 vs 0.06 control; prior reports had high urinary 5-oxoproline with normal glutathione synthase levels and usually no metabolic acidemia (pqac-00000000, pqac-00000004) | Supports true inherited OPLAH deficiency with highly variable expression; authors note debate over whether some prior neurologic findings were due solely to OPLAH deficiency versus overlapping defects (pqac-00000000, pqac-00000004) |
| Calpena, 2012 | Human case report / short series | https://doi.org/10.1007/8904_2012_166 | 2 unrelated probands | Expected AR disorder overall; prior homozygous p.H870Pfs truncating mutation noted in literature; in this report only single heterozygous missense OPLAH changes found: c.969C>A (p.S323R) and c.3265G>A (p.V1089I) (pqac-00000001, pqac-00000005) | Clinical significance uncertain; literature cited as inconsistent, with renal stones, mental retardation, neonatal hypoglycaemia, microcytic anemia, microcephaly, and episodic seizures in an infant; present series did not clearly support symptomatic enzymopathy, and one infant’s oxoprolinuria normalized by age 1 year (pqac-00000001, pqac-00000005) | Very high urinary pyroglutamic acid/5-oxoproline: one proband 13,208 mmol/mol creatinine, second sample 7,931 mmol/mol creatinine; decompensation examples 7,828 and 3,255 mmol/mol creatinine; later normalization example 9 mmol/mol creatinine at 1 year (reference <10); blood glutathione within reference range (e.g., 3.2 mmol/L, 2.45 mmol/L) (pqac-00000001, pqac-00000005) | Interpreted largely as a benign biochemical condition / uncertain pathogenic significance, especially for isolated heterozygous missense findings; authors suggest oxoprolinuria may sometimes be an epiphenomenon (pqac-00000001, pqac-00000005) |
| Kasapkara, 2024 | Human case report with literature review | https://doi.org/10.1159/000536295 | 1 symptomatic child; review text notes roughly 20 patients reported overall | Homozygous OPLAH variant NM_017570.5:c.1909C>T (p.Arg637Trp) in child of consanguineous parents; ACMG classification reported as likely pathogenic; review also lists additional reported homozygous/compound heterozygous/heterozygous variants in prior patients (pqac-00000002, pqac-00000003, pqac-00000006, pqac-00000007) | Epilepsy, speech difficulty/delay, developmental delay, postnatal macrocephaly, hydrocephalus, progressive cerebral atrophy, hypomyelination, ventriculomegaly, corpus callosum hypoplasia; review notes broader spectrum including psychomotor retardation, hypotonia, feeding problems, vomiting, recurrent pneumonia, severe respiratory events, microcephaly or macrocephaly, leukodystrophy/delayed myelination, mild metabolic acidosis (pqac-00000003, pqac-00000006, pqac-00000007) | Urine 5-oxoproline 177.9 mmol/mol creatinine (reference 25.8–92.2); three additional samples ranged 105.79–243.13 mmol/mol creatinine; diagnosis supported by persistent 5-oxoprolinuria and normal GSS analysis (pqac-00000003, pqac-00000007) | Authors argue inherited OPLAH deficiency is “not a benign biochemical condition” and recommend molecular testing/screening in symptomatic patients with persistent 5-oxoprolinuria (pqac-00000002, pqac-00000003, pqac-00000007) |


*Table: This table summarizes the key published human evidence for inherited OPLAH deficiency/5-oxoprolinuria from the three provided studies. It highlights the shift from viewing the condition as a potentially benign biochemical finding toward recognition that some patients have clear neurologic and structural brain manifestations.*