The transporter, OCTN2, is located in the apical membrane of the renal tubular cells, where it plays a role in tubular reabsorption.The defective OCTN2 is unable to recapture carnitine prior to its excretion in urine, leading to the characteristic biochemical findings of massively increased urine carnitine levels and significantly decreased plasma carnitine levels. Decreased levels of plasma carnitine inhibit fatty acid oxidation during times of excessive energy demand. Carnitine is needed to transport long chain fatty acids into the mitochondria, where they can be broken down to produce acetyl-CoA. Individuals with SPCD cannot produce ketone bodies as energy due to the interruption of fatty acid oxidation. Although SPCD is an autosomal recessive condition, heterozygotes have been shown to be at an increased risk for developing benign cardiomyopathy compared to wild type individuals. Diagnosis
The first suspicion of SPCD in a patient with a non-specific presentation is an extremely low plasma carnitine level. When combined with an increased concentration of carnitine in urine, the suspicion of SPCD can often be confirmed by either molecular testing or functional studies assessing the uptake of carnitine in cultured fibroblasts. Treatment
Identification of patients presymptomatically via newborn screening has allowed early intervention and treatment. Treatment for SPCD involves high dose carnitine supplementation, which must be continued for life. Individuals who are identified and treated at birth have very good outcomes, including the prevention of cardiomyopathy. Mothers who are identified after a positive newborn screen but are otherwise asymptomatic are typically offered carnitine supplementation as well.
Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating complement and damaging the glomeruli. MPGN accounts for approximately 4% of primary renal causes of nephrotic syndrome in children and 7% in adults.It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not. Type
There are three types of MPGN, but this classification is becoming obsolete as the causes of this pattern are becoming understood. Type I
Type I, the most common by far, is caused by immune complexes depositing in the kidney. It is characterised by subendothelial and mesangial immune deposits. It is believed to be associated with the classical complement pathway. Type II
Also called recently as ‘C3 nephropathy’
The preferred name is "dense deposit disease." Most cases of dense deposit disease do not show a membranoproliferative pattern. A 2012 review considers DDD to be in a continuum with C3 glomerulonephritis, one reason the use of the type I to type III classification system is falling out of favour.Most cases are associated with the dysregulation of the alternative complement pathway.DDD is associated with deposition of complement C3 within the glomeruli with little or no staining for immunoglobulin. The presence of C3 without significant immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway (AP).