Distinctive symptoms of neuroferritinopathy are chorea, found in 50% of diagnosed patients, dystonia, found in 43% of patients, and parkinsonism, found in 7.5% of patients. Full control of upper limbs on the body generally remains until late onset of the disease. Over time, symptoms seen in a patient can change from one side of the body to the opposite side of the body, jumping from left to right or vice versa. Another route that the physically visible symptoms have been observed to take is the appearance, disappearance, and then reappearance once more of specific symptoms.While these symptoms are the classic indicators of neuroferritinopathy, symptoms will vary from patient to patient. Causes
Neuroferritinopathy results from abnormal brain iron accumulation. This iron accumulation is due to mutations in the FTL polypeptide, which is responsible for encoding proteins involved in iron metabolism. Neuroferritinopathy is most commonly caused by a single insertion of the nucleotide adenine into the gene for L-chain ferritin which in turn, alters the carboxyl end of the entire protein chain. However, exact location of the insertion in the exon varies by family. Neuroferritinopathy may also be caused by the insertion of two extra nucleotide bases. The insertion of bases into the L-chain ferritin gene causes the chain to lengthen and alter the sequence of the amino acids found in the gene, also known as a frameshift mutation.These mutations result in decreased iron-binding ability. The oxidative damage caused by increased iron leads to apoptosis, or programmed cell death.
Tyrosinemia or tyrosinaemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms of untreated tyrosinemia include liver and kidney disturbances. Without treatment, tyrosinemia leads to liver failure. Today, tyrosinemia is increasingly detected on newborn screening tests before any symptoms appear. With early and lifelong management involving a low-protein diet, special protein formula, and sometimes medication, people with tyrosinemia develop normally, are healthy, and live normal lives. Cause
All tyrosinemias result from dysfunction of various genes in the phenylalanine and tyrosine catabolic pathway, and are inherited in an autosomal-recessive pattern.Type I tyrosinemia results from a mutation in the FAH gene, which encodes the enzyme fumarylacetoacetase. As a result of FAH deficiency, the substrate fumarylacetoacetate can accumulate in proximal renal tubular cells and hepatocytes, resulting in damage to the kidney and liver, respectively.Type II tyrosinemia results from a mutation in the TAT gene, which encodes the enzyme tyrosine aminotransferase. As a result of TAT deficiency, the substrate tyrosine accumulates, causing ophthalmologic and dermatologic abnormalities.Type III tyrosinemia results from a mutation in the HPD gene, which encodes the enzyme 4-hydroxyphenylpyruvate dioxygenase. Type III tyrosinemia is the rarest of the three conditions, with only a few cases ever reported. Most of those cases have included intellectual disability and neurologic dysfunction.