A baby’s respiratory failure and the need for artificial ventilation were attributed to spinal muscular atrophy with respiratory distress type 1 (SMARD1), a very rare disease in which one of its two IGHMBP2 Gene mutations that have never been reported before.

“This case has expanded the knowledge of the genetic profile of SMARD1 and provides a basis for genetic testing of parents and for genetic counseling to assess the risk of fetal disease,” the researchers wrote in a report from China.

The report: “Novel mutation in IGHMBP2 Gene in spinal muscular atrophy with respiratory distress type 1: A case report”, was published in the magazine Heliyon.

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Respiratory arrest and artificial ventilation after infection in childhood

SMARD1 is caused by mutations in the IGHMBP2 Gene that causes damage to motor neurons, the nerve cells that control voluntary movement. To develop the disease, a child must have two mutated copies of the IGHMBP2 Gene, one from each biological parent.

This rare form of spinal muscular atrophy (SMA) is characterized by breathing difficulties that begin in the first weeks or months after birth, followed by progressive muscle weakness throughout the body during infancy. Without artificial ventilation, babies with SMARD1 usually do not survive the first year of life.

The girl was born with a low birth weight after a healthy pregnancy. She began breastfeeding normally, with no signs of breastfeeding difficulties. However, at around two months of age, she developed a respiratory infection, followed by difficulty breathing.

The baby’s condition continued to deteriorate, requiring intubation to keep the airway open and being placed on a ventilator to help him breathe better. Although the baby was reportedly 7 months old, he continued to require ventilation despite treatment for the infection.

Her weight and height remained below the range expected for her age, but “she was alert, active, and able to follow and fixate on visual and auditory stimuli,” the scientists wrote.

They also noted slight tremors in her face and tongue, weak and reduced muscle tone in her limbs, and limited mobility of her arms and legs. Knee and ankle reflexes were absent, but the baby could sense sensations, they added, and fat pads were visible on her second and fifth toes.

Baby inherited an IGHMBP2 mutation in each gene copy from his parents

All of these symptoms were consistent with SMARD1 and supported the diagnosis. Genetic testing revealed that the girl had inherited mutations in both copies of the gene. IGHMBP2 Gen; more specifically, c.1334A>C (p.His445Pro) was inherited from her father and c.1666C>G (p.His556Asp) from her mother.

Both mutations result in one amino acid, a building block of the protein encoded by this gene, being exchanged for another. Both parents were mutation carriers without any symptoms of the disease.

While c.1334A>C (p.His445Pro) has previously been linked to SMARD1, c.1666C>G (p.His556Asp) has not. Computer simulations predicted that this mutation probably did not affect the protein’s function, but there was too little evidence to say for sure.

“This … mutation has not previously been reported in patients with SMARD1 and is not documented in the Human Gene Mutation Database,” a collection of genetic mutations believed to underlie the hereditary disease, the scientists wrote.

Given the girl’s clinical SMARD1 symptoms, the team suspects that the newly reported mutation is likely pathogenic (disease-causing) or plays a role in the disease. “However, the pathogenic mechanism needs to be further investigated in additional patients,” they added.