Pathology of this case: What is being illustrated is a muscle biopsy under medium magnification electron microscopy. The myofibrils on the left of the picture provide the hint for identification of tissue. There are many round droplets not bounded by a membrane. These are neutral fat droplets. The storage can be well demonstrated also by oil red O stain or other stains for neutral fat droplets such as Sudan black. The accumulation of neutral fat is not specific and it can be seen in mitochondrial myopathy. However, among all of the diagnoses being listed here, this feature is most consistent with carnitine deficiency. Carnitine is needed for transmembrane transport of fatty acid into the mitochondria for beta-oxidation. Deficiency will lead to accumulation of neutral lipid in the cytoplasm. Carnitine can also give or take an acetyl group and stabilize acetyl-CoA and coenzyme A.

Pompe's disease is the infantile variant of glycogenosis (glycogen storage disease) type II due to deficiency of a-1,4-glucosidase. In contrast to other glycogenosis, this type is a lysosomal storage disease and the storage material is membrane bound.

McArdle's disease or glycogenosis (glycogen storage disease) type V is due to deficiency of the muscle isoform of phosphorylase. In contrast to Pompe's disease, the glycogen is not membrane bound. [Click here to see an image of glycogen storage]

Zellweger syndrome (Cerebrohepatorenal syndrome of Zellweger) is a peroxisomal disease that is  biochemically characterized by abnormal accumulation of very long chain fatty acid, and morphologically characterized by a neuronal migration defect, typically pachymicrogyria, affecting both the cerebral hemisphere and cerebellar hemisphere. This is the first syndrome known in which malformations of the brain and other organs are associated with an inborn error of metabolism. The peroxisomal Beta-oxidation is impaired and lead to the accumulation of saturated very long chain (over 22 carbon) fatty acid (VLCFA). Measurment of VLCFA level is the mainstay of biochemical diagnosis. It is transmitted in an autosomal recessive trait. Its main microscopic feature is abnormal assembly of persoximes. At ultrastructural level, various inclusion bodies have been described. Macrophages containing lipid droplets and lamellae are present.

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