The medium-chain acyl-CoA dehydrogenase (MCAD) deficiency of mitochondrial beta oxidation has been identified in two asymptomatic siblings in a family in which two previous deaths had been recorded, one attributed to sudden infant death syndrome and the other to Reye syndrome.
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a disorder of fatty acid oxidation that has been the most common such metabolic disorder found in series of SIDS victims.
The present study investigated 120 well-defined cases of sudden infant death syndrome in order to detect the frequency of the most common disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase (G985) compared with the frequency in the general population.
Scottish frequency of the common G985 mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene and the role of MCAD deficiency in sudden infant death syndrome (SIDS).
Re-investigations of cases of sudden infant death syndrome (SIDS) have revealed in some instances a deficiency of MCAD, suggesting that this metabolic disorder may lead to sudden infant death without prior clinical symptoms.
It is necessary to distinguish between lethal mutations leading to diseases such as MCAD and LQTS, and polymorphisms (for instance, in the IL-10 gene and mtDNA) that are normal gene variants but might be suboptimal in critical situations and thus predispose infants to sudden infant death.
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive disorder which is known to cause Reye-like syndrome in children and sudden infant death.
Recent studies show that PACAP plays a role in neonatal cardiorespiratory responses to hypoxia, hypercapnia, and hypothermia, but not hyperthermia, which is often associated with SIDS.
Whether PACAP gene abnormalities contribute to Sudden Infant Death Syndrome (SIDS) by reducing respiratory system efficacy during environmental stress remains unanswered.
Autoimmune dysfunction of certain vasoactive neuropeptides (e.g., vasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide) may be implicated in a range of disorders associated with fatigue-like states (chronic fatigue syndrome, Gulf War syndrome) and even sudden infant death syndrome (SIDS).
Also associated with SIDS were interactions between the variants rs2302475 (variant 'i') in PAC1 and rs8192597 and rs2856966 in PACAP among Caucasians (p < 0.02) and rs2267734 (variant 'q') in PAC1 and rs1893154 in PACAP among African Americans (p < 0.01).
All these changes as well as eventual PACAP abnormalities could result in disturbed homeostatic control of the cardiovascular and respiratory responses of SIDS victims, which, combined with the nicotine effects and metabolic trauma, finally lead to death in these often genetically predisposed children.
Pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate receptor 1 (PAC1), have been implicated in the pathophysiology of the Sudden Infant Death Syndrome (SIDS).
No specific data is currently available regarding the presence of PACAP or receptors in key respiratory centers, although it is known that neonatal PACAP knock-out mice die suddenly in a manner similar to sudden infant death syndrome (SIDS).
These findings suggest that PAC1 plays the principal role in mediating the cardiorespiratory effects of PACAP in response to hypoxic stress during neonatal development and that defective PACAP signaling via PAC1 may contribute to the pathogenesis of SIDS.
Overall, this study does not support a strong association between variants in the PAC1 gene and SIDS; however, a number of potential associations between race-specific variants and SIDS were identified that warrant targeted investigations in future studies.
These findings suggest that PAC1 plays the principal role in mediating the cardiorespiratory effects of PACAP in response to hypoxic stress during neonatal development and that defective PACAP signaling via PAC1 may contribute to the pathogenesis of SIDS.
Pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate receptor 1 (PAC1), have been implicated in the pathophysiology of the Sudden Infant Death Syndrome (SIDS).