Porphyria diagnosed in man living with SMA since childhood

Odds of two genetic rare conditions about those of 'two pins colliding in mid-air'

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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In an extremely unusual case, a young man in Turkey diagnosed as a child with spinal muscular atrophy, a rare genetic neurological disease, was also found to have porphyria.

“An individual carrying mutated genes for both diseases is similar to the odds of two pins colliding in mid-air,” its scientists wrote, adding that “further gene analyses are needed in patients that are known to suffer from a congenitally inherited disease to uncover a possible secondary disease.”

His case was described in the report, “Acute intermittent porphyria and spinal muscular atrophy: two rare diseases seen in one patient,” published in the Journal of Rare Diseases.

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Disease-causing mutations found in the patient and his mother

Acute intermittent porphyria (AIP) is one of the most common forms of porphyria. It’s caused by mutations in the HMBS gene, and, like all forms of porphyria, leads to the toxic buildup of molecules called porphyrins in body tissues and organs.

Spinal muscular atrophy, or SMA, is generally caused by mutations in a gene called SMN1. This disorder is characterized by the progressive death and degeneration of motor neurons — the specialized nerve cells that control voluntary movements — leading to symptoms of muscle weakness and atrophy.

Both AIP and SMA are individually rare, and having both diseases is unheard of, at least until now. Scientists in Turkey described the case of a 27-year-old man who was found to have mutations causing both disorders.

“To our knowledge, this is the first case ever reported of an individual possessing mutations for both SMA and porphyria,” they wrote.

At age 4, the boy was brought to a hospital with complaints of fatigue and weakness in his limbs, particularly his legs. After a yearlong diagnostic journey, he was diagnosed with SMA type 3, a relatively mild disease form.

Now in his 20s, the man is able to walk, although he usually relies on a wheelchair for long distances. He works full time from home, and is a cigarette smoker.

While his family has no history of SMA, several cousins are known to have AIP. Due to the presence of the genetic disease in the family, he was screened for AIP and found to carry a disease-associated mutation in the HMBS gene. His mother also was found to carry the same mutation.

When asked, the man said he had never experienced any symptoms that would be indicative of an AIP attack, such as acute abdominal pain or constipation. His mother also didn’t recall symptoms, but she mentioned one episode of acute pain during a menstrual period — a common porphyria trigger — that at the time she had attributed to bad cramping.

Laboratory analyses of porphyria disease markers were generally within a normal range for the patient, except for a mild increase in liver damage markers documented in 2015. Researchers noted that this is consistent with his lack of symptoms, since disease markers usually only increase during an acute attack.

“Although our patient has not had an attack of porphyria until now, he might encounter an attack in the future,” the scientists wrote.

“Knowing beforehand that there is a disease that can be exacerbated by triggering factors such as smoking might facilitate the diagnostic process in the future if there are complaints and can prevent complications,” they added.