A later phase of the disease is characterized by the replacement of normal bone marrow with highly vascular fibrous tissue.Sir James Paget first suggested the disease was due to an inflammatory process. Some evidence suggests that a paramyxovirus infection is the underlying cause of Pagets disease, which may support the possible role of inflammation in the pathogenesis. However, no infectious virus has yet been isolated as a causative agent, and other evidence suggests an intrinsic hyperresponsive reaction to vitamin D and RANK ligand is the cause. Further research is therefore necessary. Diagnosis
The first clinical manifestation of Pagets disease is usually an elevated alkaline phosphatase in the blood. Pagets disease may be diagnosed using one or more of the following tests:

Pagetic bone has a characteristic appearance on X-rays. A skeletal survey is therefore indicated. An elevated level of alkaline phosphatase in the blood in combination with normal calcium, phosphate, and aminotransferase levels in an elderly patient are suggestive of Pagets disease. Markers of bone turnover in urine eg. Pyridinoline
Elevated levels of serum and urinary hydroxyproline are also found. Bone scans are useful in determining the extent and activity of the condition. If a bone scan suggests Pagets disease, the affected bone(s) should be X-rayed to confirm the diagnosis.
During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.Mutations in the HADHA or HADHB genes that cause mitochondrial trifunctional protein deficiency disrupt all functions of this enzyme complex. Without enough of this enzyme complex, long-chain fatty acids cannot be metabolized. As a result, these fatty acids are not converted to energy, which can lead to some features of this disorder. Long-chain fatty acids may also build up and damage the liver, heart, and muscles. This abnormal buildup causes other symptoms of mitochondrial trifunctional protein deficiency.The mechanism of this condition indicates that the mitochondrial trifunction protein  catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids: long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), long-chain enoyl-CoA hydratase, and long-chain thiolase activities. Trifunctional protein deficiency is characterized by decreased activity of all 3 enzymes. Clinically, trifunctional protein deficiency usually results in sudden unexplained infant death, cardiomyopathy, or skeletal myopathy. Diagnosis
Diagnosis of mitochondrial trifunctional protein deficiency is often confirmed using tandem mass spectrometry. Genetic counseling is available for this condition. Additionally the following exams are available:

CBC
Urine test

Treatment
Management for mitochondrial trifunctional protein deficiency entails the following:
Avoiding factors that might precipitate condition
Glucose
Low fat/high carbohydrate nutrition

See also
Long-chain acyl-CoA dehydrogenase

References
Further reading
Nyhan, William L.; Hoffman, Georg F.; Barshop, Bruce A.; Al-Aqeel, Aida I. (2012). Atlas of Inherited Metabolic Diseases 3E. CRC Press. ISBN 9781444149487. Thöny, Beat; Duran, Marinus; Gibson, K. Michael; Dionisi-Vici, Carlo (2013). Physicians Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. Springer. ISBN 9783642403378.