Hydrogen sulfide (H2S) poisoning involves a risk of hypoxic brain damage. Six patients who lost consciousness due to H2S poisoning are described. The symptoms varied from anosmia in the patient with the shortest but highest exposure to delayed neurological deterioration in the patient with the longest exposure. The two patients with the most serious symptoms developed pulmonary edema, which may have prolonged the hypoxia. The patients were reexaminated 5 years or more after the poisoning. The five patients who had been unconscious in H2S atmosphere for from 5 to 15-20 min showed persisting impairment at neurological and neuropsychological re-examination. Memory and motor function were most affected. One patient was seriously demented. Recent reports of large groups of H2S-poisoned workers probably underestimate the risk of sequelae, due to the inclusion of cases with exposure of short duration and lack of follow-up.

A shipyard worker was poisoned by hydrogen sulfide (H2S), and rescued after 15-20 min. He regained consciousness after 2 days. Three days later his condition deteriorated, and he was more or less comatose for a month. When he woke up, he was amnesic, nearly blind, had reduced hearing, and had a moderate spastic tetraparesis and ataxia. Two months after the accident, he had greatly improved. Audiograms showed hearing loss with maximum at 2000 Hz and significantly poorer speech discrimination. EEG showed generalized dysrhythmia. At follow-up 5 years later he had not been able to resume his work, and had slight motor, memory and visual symptoms. CT and MRI showed slight cerebral atrophy. EEG and evoked responses were normal.

Import of peroxisomal matrix proteins, crucial for peroxisome biogenesis, is mediated by the cytosolic receptors PEX5 and PEX7 that recognize proteins carrying peroxisomal targeting signals 1 or 2 (PTS1 or PTS2), respectively. Mutations in PEX5 or 12 other PEX genes cause peroxisome biogenesis disorders, collectively named the Zellweger spectrum disorders (ZSDs), whereas mutations in PEX7 cause rhizomelic chondrodysplasia punctata type 1 (RCDP1). Three additional RCDP types, RCDP2-3-4, are caused, respectively, by mutations in GNPAT, AGPS and FAR1, encoding enzymes involved in plasmalogen biosynthesis. Here we report a fifth type of RCDP (RCDP5) caused by a novel mutation in PEX5. In four patients with RCDP from two independent families, we identified a homozygous frame shift mutation c.722dupA (p.Val242Glyfs(∗)33) in PEX5 (GenBank: NM_001131023.1). PEX5 encodes two isoforms, PEX5L and PEX5S, and we show that the c.722dupA mutation, located in the PEX5L-specific exon 9, results in loss of PEX5L only. Both PEX5 isoforms recognize PTS1-tagged proteins, but PEX5L is also a co-receptor for PTS2-tagged proteins. Previous patients with PEX5 mutations had ZSD, mainly due to deficient import of PTS1-tagged proteins. Similarly to mutations in PEX7, loss of PEX5L results in deficient import of PTS2-tagged proteins only, thus causing RCDP instead of ZSD. We demonstrate that PEX5L expression restores the import of PTS2-tagged proteins in patient fibroblasts. Due to the biochemical overlap between RCDP1 and RCDP5, sequencing of PEX7 and exon 9 in PEX5 should be performed in patients with a selective defect in the import of PTS2-tagged proteins.

We report of a spinocerebellar ataxia (SCA)27 in a daughter and her mother whose karyotype is 46, XX t(5;13)(q31.2;q33.1). The translocation breakpoint is identical in both patients, disrupting the gene-encoding fibroblast growth factor 14 isoform b (FGF14-1b). Clinically, both show signs of SCA, although the daughter is the most affected with early onset cerebellar ataxia, microcephaly, and severe mental retardation. FGF14-1b is the predominant isoform in brain, where it interacts with the voltage gated Na channel. Fgf14(-/-) mice develop ataxia and paroxysmal dyskinesia and have cognitive deficits. One missense and one non-sense mutation in FGF14 have previously been linked to SCA27. Truncation of one allele in our patients suggests that haploinsuffiency of FGF14 can cause SCA27.