The case report, “Whole Exome Sequencing Identified a Novel Heterozygous Mutation in HMBS Gene in a Chinese Patient With Acute Intermittent Porphyria With Rare Type of Mild Anemia,” was published in the journal Frontiers in Genetics.
Acute intermittent porphyria is a rare form of acute porphyria that is caused by alteration of the HMBS gene sequence. About 360 genetic mutations have been reported. The disease can manifest with a broad spectrum of symptoms, and can be life-threatening as it can affect the central nervous system.
In this case, the man started to experience the symptoms at age 26. He complaining of abdominal pain accompanied by nausea and constipation, and was hospitalized.
A first physical examination showed he had high blood pressure and a fast heart rate. His sodium blood levels were also lower than normal, but no other abnormalities were reported.
Based on his symptoms, an abdominal X-ray and gastro-endoscopy were performed, but no changes were noted. He was discharged and sent home without a diagnosis.
His symptoms persisted, and six months later he went back to the hospital with the same complains. He now had extremely low serum sodium levels, which led to frequent seizures. He also had mild anemia and chronic renal failure with high blood levels of creatinine and urea nitrogen.
Additional analysis failed to find any changes in cerebral spinal fluid (CSF) or in any hormone-secretory gland that could help explain all these symptoms.
However, the researchers found that he had high levels of protoporphyrin in red blood cells (erythrocyte), as well as high urine porphobilinogen (PBG) and uroporphyrin. These findings led to the final diagnosis of acute intermittent porphyria.
He was treated with intravenous injection of 250 mg glucose, with restricted fluid intake. After treatment, his status significantly improved and his blood sodium levels recovered to within normal values.
Because acute intermittent porphyria is a genetic disorder and none of the patient’s family members was symptomatic, the team decided to perform a genetic analysis.
The patient was found to have a new single-base deletion in the HMBS gene (c.809delC), which resulted in the production of a shortened version of the protein. Comparison with reported data showed the identified mutation was not previously linked to the disease, and had not been detected in healthy individuals.
This report adds another genetic variant to “the mutational spectra of HMBS gene related [to] acute intermittent porphyria,” which is relevant “for screening and genetic diagnosis” of the disease, the researchers said.