Opportunistic ship source level measurements in the Western Canadian Arctica).

Increased ship traffic due to climate change increases underwater noise in the Arctic. Therefore, accurate measurements of underwater radiated noise are necessary to map marine sound and quantify shipping's impact on the Arctic ecosystem. This paper presents a method to calculate opportunistic source levels (SLs) using passive acoustic data collected at six locations in the Western Canadian Arctic from 2018 to 2022. Based on Automatic Identification System data, acoustic data, and a hybrid sound propagation model, the SLs of individual ships were calculated within a 5 km radius of each measurement site. A total of 66 measurements were obtained from 11 unique vessels, with multiple measurements from the same vessel type contributing more SLs. For vessels with propeller cavitation, measured SLs correlated positively with vessel parameters, such as speed and length. SL and speed did not correlate well for vessels without propeller cavitation. The JOMOPANS-ECHO SL model produced good agreement with measured SL for certain ship types (container ships, a tanker, and a passenger vessel). However, significant differences between measurement and model are evident for certain polar-class ships that travel in the Arctic, indicating that more controlled SL measurements are needed.

A test of the thermal coadaptation hypothesis with ultimate measures of fitness in flour beetles.

Whole-organism performance of ectotherms depends on body temperature, which is tightly linked to environmental temperatures. Individuals attempting to optimize fitness must thus select appropriate temperatures. The thermal coadaptation hypothesis posits that To for traits closely linked to fitness should match temperatures selected by a species (Tset) and should coevolve with Tset. To may mismatch Tset if the thermal reaction norm for fitness is asymmetric. In this study, we examined six traits related to fitness in red and in confused flour beetles (Tribolium castaneum and T. confusum, respectively), including longevity, lifetime reproductive success, reproductive rate, and development time at four temperatures between 23 and 32°C. For reproductive traits, To matched Tset whereas for longevity To was lower than Tset. Tribolium species have a strongly r-selected life history strategy, therefore reproductive traits are likely more tightly linked to fitness than longevity due to high predation rates at early life stages. We therefore provide support for the thermal coadaptation hypothesis for reproductive traits that are tightly linked to fitness. Our results highlight the importance of knowing the relationships of traits to fitness when studying thermal physiology.

Increased subcortical oligodendroglia-like cells in pharmacoresistant focal epilepsy in children correlate with extensive epileptogenic zones.

OBJECTIVE: Cortical resections in epilepsy surgery tend to involve multiple lobes in children, compared to adults, partly due to underlying pathology. Oligodendroglia-like cells (OLCs) have been observed in surgical specimens from children with pharmacoresistant epilepsy. We hypothesize that OLCs recruit multiple-lobe epileptogenic zones in pediatric pharmacoresistant focal epilepsy. METHODS: We examined the surgical specimens from 30 children who underwent epilepsy surgery (1.8- to 16.9-years-old; mean age 9.7 years). Immunohistochemical assays of OLCs were performed using Olig2, which is a marker of OLC. OLC populations in three sites (gray matter, gray-white matter junction, and white matter) were counted. We also performed immunohistochemical staining with neuronal nuclear antigen (NeuN) and glial fibrillary acidic protein (GFAP) for neuronal and astroglial markers, respectively. NeuN- and GFAP-positive cells were distinguished from OLCs. OLC results were compared with seizure types, scalp and intracranial video-electroencephalography (EEG), magnetic resonance imaging (MRI), surgical resection area, histopathologic diagnosis, and seizure outcome. RESULTS: Histopathologic diagnosis consisted of 14 cases of focal cortical dysplasia (FCD; type I; 4, type II; 9, type III; one); 6 cases of oligodendrogliosis; 6 cases of astrocytic gliosis; 2 cases of hyaline protoplasmic astrocytopathy; and 2 cases of tuberous sclerosis. Fifteen children (50%) underwent multiple-lobe resections after intracranial video-EEG. There was a positive correlation between the number of resected electrodes and the OLC population in the white matter (correlation coefficient 0.581, p = 0.001) and at the gray-white matter junction- (correlation coefficient 0.426, p = 0.027). OLC populations in both areas were increased significantly in nine children with epileptic spasms (ES) (gray-white matter junction [p = 0.021] and white matter [p = 0.025]), and nine nonfocal ictal scalp EEG findings (gray-white matter junction [p = 0.04] and white matter [p = 0.042]). The OLC population in white matter was significantly increased in children with 11 nonfocal interictal scalp EEG findings (p = 0.01), with 15 multiple-lobe resections (p = 0.028). SIGNIFICANCE: Pharmacoresistant epilepsy in children with increased OLCs presented with nonfocal epileptiform discharges on scalp EEG and ES, and they required multiple-lobe resections. We found increased populations of subcortical OLCs in the extensive epileptogenic zone.

Differential fitness in field and forest explains density-independent habitat selection by gartersnakes.

The ideal free distribution concept predicts that organisms will distribute themselves between habitats in a density-dependent manner so that individuals, on average, achieve the same fitness in each habitat. In ectotherms, environmental temperature has a strong impact on fitness, but temperature is not depletable and thus not density dependent. Can density-dependent habitat selection occur in ectotherms when habitats differ in thermal quality? We used an observational study of habitat selection by small snakes in field and forest, followed by manipulative habitat selection and fitness experiments with common gartersnakes in enclosures in field and forest to test this hypothesis. Snakes were much more abundant in the field, the habitat with superior thermal quality, than in the forest. Gartersnakes in our controlled experiment only used the forest habitat when snake density was highest and when food was more abundant in the forest; habitat selection was largely density independent, although there was weak evidence of density dependence. No female gartersnake gave birth in the forest enclosures, whereas half of the females gave birth in the field enclosures. Growth rates of females were higher in field than in forest enclosures. Overall, our data indicate that temperature appears to be the most important factor driving the habitat selection of gartersnakes, likely because temperature was more limiting than food in our study system. Snakes, or at least temperate snakes, may naturally exist at population densities low enough that they do not exhibit density-dependent habitat selection.

Missense mutations in ß-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) cause Walker-Warburg syndrome.

Several known or putative glycosyltransferases are required for the synthesis of laminin-binding glycans on alpha-dystroglycan (αDG), including POMT1, POMT2, POMGnT1, LARGE, Fukutin, FKRP, ISPD and GTDC2. Mutations in these glycosyltransferase genes result in defective αDG glycosylation and reduced ligand binding by αDG causing a clinically heterogeneous group of congenital muscular dystrophies, commonly referred to as dystroglycanopathies. The most severe clinical form, Walker-Warburg syndrome (WWS), is characterized by congenital muscular dystrophy and severe neurological and ophthalmological defects. Here, we report two homozygous missense mutations in the ß-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) gene in a family affected with WWS. Functional studies confirmed the pathogenicity of the mutations. First, expression of wild-type but not mutant B3GNT1 in human prostate cancer (PC3) cells led to increased levels of αDG glycosylation. Second, morpholino knockdown of the zebrafish b3gnt1 orthologue caused characteristic muscular defects and reduced αDG glycosylation. These functional studies identify an important role of B3GNT1 in the synthesis of the uncharacterized laminin-binding glycan of αDG and implicate B3GNT1 as a novel causative gene for WWS.

A stringent test of the thermal coadaptation hypothesis in flour beetles.

Whole-organism performance depends on body temperature and ectotherms have variable body temperatures. The thermal coadaptation hypothesis posits that thermal reaction norms have coevolved with thermal preference such that organisms attain optimal performance under a narrow range of body temperatures commonly experienced in the wild. Since thermal reaction norms are often similar, researchers interested in the effects of temperature on fitness often use one easily measured thermal reaction norm, such as locomotor performance, and assume it is a good proxy for fitness when testing the thermal coadaptation hypothesis. The extent to which this assumption holds, however, is often untested. In this study, we provide a stringent test of the thermal coadaptation hypothesis in red and in confused flour beetles by comparing the thermal reaction norm for reproductive output to the preferred body temperature range. We also test the assumption that locomotor performance can serve as a proxy for the thermal reaction norm for reproductive output, a more ultimate index of fitness. In both species, we measured the number of eggs laid, righting time, and sprint speed at eight temperatures, as well as the thermal preference in a thermal gradient. The number of eggs laid increased with female sprint speed and with male righting time, and all three performances had similar thermal reaction norms, with 80% of the maximum achieved between 23 and 37°C. Red flour beetles had preferred body temperatures that matched the optimal temperature for performance; confused flour beetles had lower preferred body temperature than the optimal temperature for performance. We found support for the assumption that locomotor performance can serve as a proxy for reproductive output in flour beetles, but we only found evidence for thermal coadaptation in one of the two species.

CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity.

Amplification of the C19MC oncogenic miRNA cluster and high LIN28 expression has been linked to a distinctly aggressive group of cerebral CNS-PNETs (group 1 CNS-PNETs) arising in young children. In this study, we sought to evaluate the diagnostic specificity of C19MC and LIN28, and the clinical and biological spectra of C19MC amplified and/or LIN28+ CNS-PNETs. We interrogated 450 pediatric brain tumors using FISH and IHC analyses and demonstrate that C19MC alteration is restricted to a sub-group of CNS-PNETs with high LIN28 expression; however, LIN28 immunopositivity was not exclusive to CNS-PNETs but was also detected in a proportion of other malignant pediatric brain tumors including rhabdoid brain tumors and malignant gliomas. C19MC amplified/LIN28+ group 1 CNS-PNETs arose predominantly in children <4 years old; a majority arose in the cerebrum but 24 % (13/54) of tumors had extra-cerebral origins. Notably, group 1 CNS-PNETs encompassed several histologic classes including embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma, ependymoblastoma and CNS-PNETs with variable differentiation. Strikingly, gene expression and methylation profiling analyses revealed a common molecular signature enriched for primitive neural features, high LIN28/LIN28B and DNMT3B expression for all group 1 CNS-PNETs regardless of location or tumor histology. Our collective findings suggest that current known histologic categories of CNS-PNETs which include ETANTRs, medulloepitheliomas, ependymoblastomas in various CNS locations, comprise a common molecular and diagnostic entity and identify inhibitors of the LIN28/let7/PI3K/mTOR axis and DNMT3B as promising therapeutics for this distinct histogenetic entity.

Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies.

BACKGROUND: Retinoblastoma is the childhood retinal cancer that defined tumour-suppressor genes. Previous work shows that mutation of both alleles of the RB1 retinoblastoma suppressor gene initiates disease. We aimed to characterise non-familial retinoblastoma tumours with no detectable RB1 mutations. METHODS: Of 1068 unilateral non-familial retinoblastoma tumours, we compared those with no evidence of RB1 mutations (RB1(+/+)) with tumours carrying a mutation in both alleles (RB1(-/-)). We analysed genomic copy number, RB1 gene expression and protein function, retinal gene expression, histological features, and clinical data. FINDINGS: No RB1 mutations (RB1(+/+)) were reported in 29 (2·7%) of 1068 unilateral retinoblastoma tumours. 15 of the 29 RB1(+/+) tumours had high-level MYCN oncogene amplification (28-121 copies; RB1(+/+)MYCN(A)), whereas none of 93 RB1(-/-) primary tumours tested showed MYCN amplification (p<0·0001). RB1(+/+)MYCN(A) tumours expressed functional RB1 protein, had fewer overall genomic copy-number changes in genes characteristic of retinoblastoma than did RB1(-/-) tumours, and showed distinct aggressive histological features. MYCN amplification was the sole copy-number change in one RB1(+/+)MYCN(A) retinoblastoma. One additional MYCN(A) tumour was discovered after the initial frequencies were determined, and this is included in further analyses. Median age at diagnosis of the 17 children with RB1(+/+)MYCN(A) tumours was 4·5 months (IQR 3·5-10), compared with 24 months (15-37) for 79 children with non-familial unilateral RB1(-/-) retinoblastoma. INTERPRETATION: Amplification of the MYCN oncogene might initiate retinoblastoma in the presence of non-mutated RB1 genes. These unilateral RB1(+/+)MYCN(A) retinoblastomas are characterised by distinct histological features, only a few of the genomic copy-number changes that are characteristic of retinoblastoma, and very early age of diagnosis. FUNDING: National Cancer Institute-National Institutes of Health, Canadian Institutes of Health Research, German Research Foundation, Canadian Retinoblastoma Society, Hyland Foundation, Toronto Netralaya and Doctors Lions Clubs, Ontario Ministry of Health and Long Term Care, UK-Essen, and Foundations Avanti-STR and KiKa.

Boat noise impedes vocalizations of wild plainfin midshipman fish.

Marine noise is recognised as a growing threat that can induce maladaptive behavioural changes in many aquatic animals, including fishes. The plainfin midshipman is a soniferous fish with a prolonged breeding period, during which males produce tonal hums that attract females, and grunts and growls during agonistic interactions. In this study, we used acoustic recordings to assess the effects of boat noise on the presence, peak frequencies, and durations of plainfin midshipman calls in the wild. We found that all three call types were less likely to occur, and the peak frequencies of hums and grunts increased in the presence of boat noise. We also show that loud and quiet boat noise affected plainfin midshipman vocalizations similarly. As anthropogenic noise is likely to increase in the ocean, it will be important to understand how such noise can affect communication systems, and consequently population health and resiliency.

The Arctic marine soundscape of the Amundsen Gulf, Western Canadian Arctic.

The underwater soundscape, a habitat component for Arctic marine mammals, is shifting. We examined the drivers of the underwater soundscape at three sites in the Amundsen Gulf, Northwest Territories, Canada from 2018 to 2019 and estimated the contribution of abiotic and biotic sources between 20 Hz and 24 kHz. Higher wind speeds and the presence of bearded seal (Erignathus barbatus) vocalizations led to increased SPL (0.41 dB/km/h and 3.87 dB, respectively), while higher ice concentration and air temperature led to decreased SPL (-0.39 dB/% and - 0.096 dB/°C, respectively). Other marine mammals did not significantly impact the ambient soundscape. The presence of vessel traffic led to increased SPLs (12.37 dB) but was quieter at distances farther from the recorder (-2.57 dB/log m). The presence of high frequency and broadband signals produced by ice led to increased SPLs (7.60 dB and 10.16 dB, respectively).

Spinal clear cell meningioma in a 3-year-old: a case report.

Clear cell meningioma (CCM) is an aggressive meningioma variant with a tendency to early recurrence posing a challenge to its treatment. Although spinal meningiomas are uncommon in children, this rare entity has been described as the most common variant of spinal meningiomas in the pediatric age group. We present the case of a 3-year-old with a confirmed lumbar spine CCM and discuss the problems encountered in the management of this disease.

No accumulation of microplastics detected in western Canadian ringed seals (Pusa hispida).

Ringed seals (Pusa hispida) play a crucial role in Arctic food webs as important pelagic predators and represent an essential component of Inuvialuit culture and food security. Plastic pollution is recognized as a global threat of concern, and Arctic regions may act as sinks for anthropogenic debris. To date, mixed evidence exists concerning the propensity for Canadian Arctic marine mammals to ingest and retain plastic. Our study builds on existing literature by offering the first assessment of plastic ingestion in ringed seals harvested in the western Canadian Arctic. We detected no evidence of microplastic (particles ≥80 µm) retention in the stomachs of ten ringed seals from the Inuvialuit Settlement Region (ISR) in the Northwest Territories, Canada. These results are consistent with previous studies that have found that some marine mammals do not accumulate microplastics in evaluated regions.

Abnormal corpus callosum in neonates after hypoxic-ischemic injury.

BACKGROUND: Literature regarding callosal injury after hypoxic-ischemic injury (HII) is scant. OBJECTIVE: To present the MRI and US findings of callosal injury after HII. MATERIALS AND METHODS: MRI and US studies of 76 neonates were evaluated for HII and 53 were considered positive. RESULTS: Of the 53 neonates with HII, 40 demonstrated restricted diffusion on DWI; of these, 30 revealed callosal involvement. Nine of the 13 neonates with normal DWI, whose routine MRI images were compatible with HII, were imaged after 1 week of age. Five out of ten neonates imaged during the 1st week of life who did not show callosal restriction on DWI had predominantly basal ganglia injury. Callosal US images were regarded as abnormal in 16 out of the 53 neonates with HII, 15 of which revealed concomitant restricted diffusion on DWI. CONCLUSION: Callosal injuries are common after HII. DWI is effective in confirming these injuries and easily demonstrates injury if performed prior to 1 week of age. The restricted diffusion demonstrated after this time could be attributed to continued injury. US is not a sensitive modality for callosal injury detection; however, abnormally increased callosal echogenicity might be a specific marker of injury in this setting.

Brain biopsy in children with primary small-vessel central nervous system vasculitis.

OBJECTIVE: Primary angiitis of the central nervous system in childhood (cPACNS) is an immune-mediated inflammatory process directed toward blood vessels in the central nervous system. It has been associated with variable clinical and radiological presentations, and devastating consequences without treatment. Brain biopsy is required for definitive diagnosis. The objective of this study was to characterize the clinical and histopathological features of brain biopsies in small-vessel cPACNS (SVcPACNS). METHODS: A single-center prospective cohort study of children diagnosed with cPACNS from 1998 to 2008 was performed. All patients with negative cerebral angiography and brain biopsy were included. Patient data were reviewed for clinical, laboratory, and radiological characteristics at presentation. Standardized brain biopsy review protocols were established, with independent analysis by 2 neuropathologists. Histopathology was correlated with collected clinical data. RESULTS: A total of 13 SVcPACNS patients were included. Ages ranged from 5 to 17 years. Presenting features included seizures (85%), headache (62%), and cognitive decline (54%). Brain biopsy confirmed SVcPACNS in 11 patients with intramural lymphocytic infiltrate. Two had nonspecific perivascular inflammation only. All 6 nonlesional biopsies yielded a diagnosis of SVcPACNS. Lack of specific histological features correlated with prolonged time to biopsy, prior steroid treatment, and inadequate specimen sampling. INTERPRETATION: In children presenting with new onset severe headaches, seizures, or cognitive decline, SVcPACNS and brain biopsy should be considered. Lesional biopsies are preferred; however, nonlesional biopsies may succeed in yielding the diagnosis. Steroid treatment prior to biopsy and inadequate biopsy sampling may obscure the diagnosis in true cases of SVcPACNS.

Further expansion of the phenotypic spectrum associated with mutations in ALDH18A1, encoding Δ¹-pyrroline-5-carboxylate synthase (P5CS).

We report on the third case of cutis laxa and progeroid features caused by a homozygous mutation in ALDH18A1 that encodes Δ¹-pyrroline-5-carboxylate-synthase (P5CS). This severely affected child, born to consanguineous parents of Pakistani origin, presented with lax, wrinkled and thin skin with dilated and tortuous subcutaneous blood vessels, corneal clouding, and hypotonia. The child had severe global developmental delay and feeding difficulties and died in infancy for an unknown reason. The proband was homozygous for a mutation in ALDH18A1, c.1923 + 1G > A which results in the production of two anomalous transcripts that are predicted to encode proteins lacking the catalytic site for the enzyme. The cellular phenotype is characterized by diminished production of collagen types I and III, altered elastin ultrastructure, and diminished cell proliferation of cultured dermal fibroblasts. This severe clinical and cellular phenotype overlaps with a broad group of neurocutaneous syndromes that include cutis laxa type II, wrinkly skin syndrome, de Barsy syndrome, and gerodermia osteodysplastica. The findings presented here emphasize the pleiotropic presentation of this group of conditions and suggest that multiple components of the extracellular matrix are perturbed in these disorders.

Protein deficiency, but not zinc deficiency, reduces recovery of type 1 and type 2 muscle fibre diameters in the gastrocnemius muscle of growing rats.

The present study examines the effects of protein- and energy-type malnutrition in combination with Zn deficiency on the growth, serum insulin-like growth factor-1 (IGF-1), gastrocnemius muscle mass and fibre diameter of growing rats during a deficiency phase followed by nutritional rehabilitation. Rats (3-weeks old) were randomly assigned to baseline, or Zn-deficient (Z, < 1 mg Zn/kg), protein-deficient (P, 20 g protein/kg), combined Zn- and protein-deficient (ZP), energy-deficient (E, feed intake pair-fed to Z) or control (C, 30 mg Zn/kg and 170 g protein/kg) groups for a 3-week deficiency phase, followed by a 3-week repletion phase with the control diet. ATPase histochemical staining at pH 9·4 was used to differentiate type 1 and type 2 muscle fibres. After the deficiency phase, the ZP and P groups had lower body weight and smaller gastrocnemius muscle mass than the Z and E groups. Type 1 and 2 muscle fibre diameters (T1- and T2-MFD, respectively) were reduced in the ZP, P and Z groups compared with the E and C groups. Serum Zn was reduced in the ZP, P and Z groups, but serum IGF-1 was lowest in the Z and E groups. After the repletion phase, T1-MFD did not recover in the P and E groups nor T2-MFD in the P group, despite the P and E groups having a better recovery of body weight. In summary, previous protein deficiency, but not Zn deficiency, limited the recovery of both T1- and T2-MFD during nutritional repletion. The quality of skeletal muscle recovery in the malnourished groups was not associated with body weight, muscle mass, serum Zn or IGF-1 concentrations.

The sources and prevalence of anthropogenic noise in Rockfish Conservation Areas with implications for marine reserve planning.

Underwater noise pollution is a recognized threat to marine life. In British Columbia, Canada, Pacific rockfish (Sebastes spp.) were historically overfished, prompting the establishment of Rockfish Conservation Areas (RCAs). However, there are no restrictions prohibiting vessel transits in RCAs. We hypothesized that RCAs do not protect rockfish from sub-lethal harm from noise. We compared noise levels at three RCAs with adjacent unprotected reference sites from August 2018-June 2019. While RCAs had lower levels of noise overall than reference sites, this trend was inconsistent; some RCA sites had higher levels of noise during certain time periods than non-RCA sites. A vessel noise detector was the best predictor of noise level over three frequency bands (20-100 Hz, 100-1000 Hz, 1-10 kHz), and predicted sound levels which could mask rockfish communication. We conclude that RCAs do not reliably protect rockfish from noise pollution, and recommend further study into potential impacts on stock recovery.

Underwater sound levels in the Canadian Arctic, 2014-2019.

The Arctic has been a refuge from anthropogenic underwater noise; however, climate change has caused summer sea ice to diminish, allowing for unprecedented access and the potential for increased underwater noise. Baseline underwater sound levels must be quantified to monitor future changes and manage underwater noise in the Arctic. We analyzed 39 passive acoustic datasets collected throughout the Canadian Arctic from 2014 to 2019 using statistical models to examine spatial and temporal trends in daily mean sound pressure levels (SPL) and quantify environmental and anthropogenic drivers of SPL. SPL (50-1000 Hz) ranged from 70 to 127 dB re 1 µPa (median = 91 dB). SPL increased as wind speed increased, but decreased as both ice concentration and air temperature increased, and SPL increased as the number of ships per day increased. This study provides a baseline for underwater sound levels in the Canadian Arctic and fills many geographic gaps on published underwater sound levels.

Loss of RB1 induces non-proliferative retinoma: increasing genomic instability correlates with progression to retinoblastoma.

Retinoblastoma clinical observations revealed the role of tumor suppressor genes in human cancer, Knudson's 'two-hit' model of cancer induction. We now demonstrate that loss of both RB1 tumor suppressor gene alleles initiates quiescent RB1(-/-) retinomas with low level genomic instability and high expression of the senescence-associated proteins p16(INK4a) and p130. Although retinomas can remain unchanged throughout life, highly proliferative, clonal and aneuploid retinoblastomas commonly emerge, exhibiting altered gene copy number and expression of oncogenes (MYCN, E2F3, DEK, KIF14 and MDM4) and tumor suppressor genes (CDH11, p75(NTR)) and reduced expression of p16(INK4a) and p130. We suggest that RB1 inactivation in developing retina induces genomic instability, but senescence can block transformation at the stage of retinoma. However, stable retinoma is rarely clinically observed because progressive genomic instability commonly leads to highly proliferative retinoblastoma.

Identification of a novel mutation in GYS1 (muscle-specific glycogen synthase) resulting in sudden cardiac death, that is diagnosable from skin fibroblasts.

We report here the identification of a patient with muscle-specific glycogen synthase deficiency. The 8-year-old patient showed no prior signs of distress before collapsing during a bout of exercise, resulting in death. Initial post-mortem analysis of tissues suggested death was due to metabolic complications of mitochondrial myopathy, but upon further examination it was found that the anomalies were indicative of mitochondrial proliferation and oxidative compensation. A homozygous two base pair deletion was identified in exon 2 of GYS1, and the parents and sibling were confirmed as heterozygous carriers of the deletion. This case highlights the importance of differentiating between mitochondrial compensatory phenomena and true mitochondrial disease, and suggests that GYS1 deficiency could be a common cause of sudden cardiac death in children. Children with abnormal cardiac responses to increased workloads as well as those with defined myocardial disease should therefore be tested for GYS1 deficiency.