α-Methylacyl-CoA racemase (AMACR) deficiency is an inherited condition that leads to functional impairment of the cellular peroxisomes and elevated levels of pristanic acid, phytanic acid, and C27-bile acid intermediates.
AMACR deficiency manifests with a varying clinical picture. A more definitive establishment of a presenting pattern has not been rendered possible, due to the lack of clinical experience with such a rare disease.
The clinical picture admittedly resembles that of Refsum disease with sensorimotor neuropathy. The latter usually presents during adulthood and can be accompanied by pigmentary retinopathy, although this is not always the case . Symptoms associated with the central or peripheral nervous system predominate and generally include encephalopathy, hearing and visual impairment or complete loss, epilepsy and cerebellar ataxia, although dysfunctions in other organs have also been reported, such as end-stage liver disease, depression and rhabdomyolysis     . Growth is usually hindered in patients affected by AMACR.
Peroxisomal disorders typically involve alterations in the cerebral structure, which can be revealed via a magnetic resonance imaging scan. Brain atrophy and neocortical dysplasia featuring perisylvian polymicrogyria and frontoparietal pachygyria are the predominant changes that are observed through the MRI scan . The structures most commonly affected include the basal ganglia, pons, and cerebral peduncles, without a definite pathophysiologic explanation.
More specifically, as in all peroxisomal disorders, characteristic findings in an MRI scan of a patient with AMACR deficiency involve the following:
Biochemical analysis of blood and urine, as well as fibroblast cultures and genetic testing, can further contribute to diagnosing AMACR deficiency.
Given that the levels of pristanic and phytanic acid greatly exceed normal values in patients with AMACR deficiency, patients are required to eliminate any source of these two types of acid from their diet. Another suggestion has been the reduction of plasma phytanic acid by plasma exchange; none of the two aforementioned therapeutic options has evinced a definitive contribution to the treatment of AMACR deficiency . Most patients receive cholic acid on a long-term basis, which may not cure the disorder, but leads to the normalization of hepatic enzymes and hinders the aggravation of symptomatology.
AMACR deficiency is a rare disorder that has been documented as few as 7 times up to this day. Due to the lack of sufficient statistic data, a unified prognosis cannot be determined. The overall course of some of the documented patients, however, is described below:
Consequently, based on the data that is available up to this day, it can be said that identical genetic mutations can lead to AMACR with a varying clinical picture, age of onset and general prognosis .
Peroxisomes are small organelles that are found in the cytoplasm and mediate the metabolism of multiple lipids, including branched fatty acids (pristanic and phytanic acid). They also take part in the process of bile acid production.
The completion of specific steps in both procedures require the presence of alpha-methyl-acyl-CoA racemase (AMACR); its deficiency leads to the accumulation of intermediate R-isomers of pristanic acid, as well as di- and tri hydrocholestanoic acids (DHCA and THCA) which are intermediate products of the bile acids biosynthesis pathway . AMACR deficiency is caused by a genetic defect, c.154T>C, which is passed down from parents to offspring in an autosomal recessive pattern.
AMACR deficiency is a rare inborn enzymic deficiency, that has been described in the literature as few as seven times up to this day. It is usually diagnosed during adulthood, with the patients suffering from additional comorbidities, such as sensorimotor neuropathy   . A single case report has described a case of AMACR deficiency diagnosed in a neonate. The c.154T>C genetic mutation that has been found to underlie the condition has been detected in as many as 6 out of the 7 known cases.
The process of β-oxidation that is carried out in the peroxisomes is an indispensable step in the rather complex procedure of molecular degradation. More specifically, β-oxidation contributes to the catabolism of branched fatty acids, VLCFA, polyunsaturated fatty acids and long-chain dicarboxylic acids; prostaglandins and leukotrienes are also catabolized in the peroxisomes . The organelles contain various enzymes, such as two acyl-CoA oxidases, two thiolase and two bifunctional enzymes that are activated by different substrates in order to mediate β-oxidation. Thus, each type of enzyme deficiency leads to the buildup of distinct substrates.
More specifically, the alpha-methylacyl-CoA racemase (AMACR) enzyme is the one that converts (2R)-methyl branched-chain fatty acids into (2S)-methyl branched-chain fatty acids, this conversion creates substrates that can successfully go through β-oxidation in the peroxisome. These newly formed substrates encompass pristanic acid and bile acid intermediates di- and tri hydrocholestanoic acids (DHCA and THCA) and, in the setting of an AMACR deficiency, they accumulate in excessive quantities .
The presence of intermediate products of β-oxidation that are unable to complete the process cause severe symptomatology, such as late-onset cerebral ataxia, adult-onset neuropathy, white matter abnormalities, recurrent encephalopathy and epilepsy    . Under some circumstances, tremor, cataract, lesions in the thalamus and pigmentary retinopathy can arise, while some individuals exhibit signs of cholestasis as early as the first days of their lives  .
α-Methylacyl-CoA racemase (AMACR) deficiency is an inborn error of the metabolic process of cholesterol. It specifically interferes with the oxidation of cholesterol's side-chain and mediates the conversion of pristanic and trihydroxycholestanoic acid into a different, stereoisomeric molecule  . The aforementioned conversion is mandatory for the β-oxidation of the C27 bile side chain that is performed in the small cytoplasmic organelles, known as peroxisomes . Thus, the absence of AMACR leads to the inability of the organism to perform the metabolic processes mentioned above and, as a result, intermediate products are released into the serum, including pristanic, di- and trihydroxycholestanoic acid  .
AMACR deficiency is a rare disorder, which is inherited via the autosomal recessive pattern of inheritance and is otherwise referred to as congenital bile acid synthesis defect type 4 (BAS defect type 4). The genetic abnormality that leads to the disease is a mutation in the AMACR gene. Very few cases have been documented in the literature up to this day, given the rarity of AMACR; only seven patients have been officially diagnosed until now; the absence of a definite prognosis, treatment plan, even a decisive clinical presentation can be attributed to this rarity  . In general, patients display neurological sequelae, including encephalopathy, peripheral neuropathy; cholestasis has also been observed.
AMACR deficiency is diagnosed by a biochemical analysis of the patient's serum and urine, brain magnetic resonance imaging, a fibroblast culture and genetic tests . Current treatment recommendations include the administration of cholic acid on a long-term basis and a dietary restriction of pristanic and phytanic acid intake, despite the fact that no definitive efficacy of the latter has been established.
Alpha-methylacyl-CoA racemase (AMACR) deficiency is a genetic disease. Individuals affected by it lack an enzyme which is vital for the metabolism of various substances, such as phytanic acid and pristanic acid. The body's inability to process these acids leads to their abnormally high accumulation in the patient's blood and various neurological complications.
AMACR deficiency is not preventable. It is either inherited from the parents in an autosomal recessive way, or it is a result of a spontaneous mutation. The autosomal recessive pattern implies that the affected individual must have inherited two defective genes, one from each parent, in order for the disease to develop.
The condition induces a variety of symptoms, which are all related to the central or peripheral nervous system and include the following:
AMACR deficiency is usually suspected when infants fail to grow, are not as active as they should be, are mentally disabled and exhibit elevated liver enzymes and an equally enlarged liver. Diagnostic tests include the detection of the presence of phytanic acid and various other metabolic products in blood that can indicate AMACR. With regard to the treatment of AMACR, patients follow a diet that has been adapted to include absolutely no phytanic and pristanic acid, even though no significant amelioration has been observed. They also receive cholic acid for long periods of time, which has been shown to stop the condition from progressing to severe stages.