PSAT1 genetic variants associated with CMT for the first time in 2 adolescents

inherited variables PSAT1 gene cause Share Marie Toth (CMT) in two adolescents, as detailed in a case study reported for the first time.

These cases are unusual, given that PSAT1 The variants are known to cause severe abnormalities of the central nervous system (CNS), or brain and spinal cord. In contrast, CMT affects peripheral nerves that run from the central nervous system to the body and extremities.

While the adolescents also suffered from ichthyosis, which is characterized by dry, thick, and scaly skin, no signs of central nervous system involvement were shown.

The patients’ motor and sensory function improved, and their ichthyosis regressed, after oral supplementation with the amino acid serine, which is the building block of protein.

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The illustration shows a patient undergoing an MRI scan.

PSAT1 variants were not previously known to cause Charcot-Marie-Tooth disease

Case Study , “nurse PSAT1 Autosomal recessive variants and variants of Charcot-Marie-Tooth disease with ichthyosis,” in the magazine Pediatric neurology.

CMT is a rare disorder that affects peripheral nerves, which control motor function (movement) and sensation. Different CMT types They are caused by mutations in several genes that either damage nerve fibers, referred to as axonal CMT, or myelin, the lipid-rich layer that insulates nerve fibres, referred to as demyelinating CMT.

Phosphoserine aminotransferase (PSAT) is an enzyme involved in the production of the amino acid serine. mutations in PSAT1 The gene, which encodes the PSAT enzyme, leads to serine deficiency and severe abnormalities of the central nervous system. PSAT1Peripheral nerve damage, but with central nervous system involvement, has recently been reported.

Researchers in China have now described two cases of unrelated adolescents carrying the pathogen PSAT1 mutations but not CNS involvement, and damage to motor and sensory nerves is consistent with axial CMT.

A 17-year-old boy was born into an unaffected family. The researchers noted that since childhood, he had dry, scaly skin and was diagnosed with ichthyosis, which usually occurs in people with serine deficiency.

At the age of 15, he began to have walking difficulties due to progressive muscle weakness and wasting of the lower extremities, which eventually spread to his forearms and hands. At the age of 16, he began using crutches due to foot deformities and began losing feeling in his limbs. At the age of 17, he was unable to walk or handle objects with his hands due to a loss of strength.

Although cognitive assessments were in the normal range, Electromyography, to assess the muscles and the nerves that control them, indicates damage. Nerve conduction studies, which measured electrical signals, revealed an absence or decreased response in peripheral nerves, while ultrasound evaluation found enlarged nerves, and muscle MRI showed fatty infiltrates, a sign of muscle wasting.

Both adolescents respond well to treatment with serine supplementation

Blood tests showed that his serine levels were in the normal range, but the boy had elevated markers indicating malnutrition. a nerve biopsy showed reduced myelinated nerve fiber density, and electron microscopy showed signs of axonal damage and death.

Genetic analysis identified a variant called c.43G>C in both PSAT1 Gene transcription (G stands for guanine and C stands for cytosine, both of which are the building blocks of DNA). His parents had the same variant in one of them PSAT1 Gene copies, vectors were unaffected. According to the researchers, this variant has been found in serine-deficient people with peripheral nerve damage. In yeast it leads to a loss of PSAT enzyme function.

His ichthyosis was successfully treated with standard care, and at age 18 the boy began taking oral serine supplements. After one year of treatment, he reported an increase in sensation and an improvement in muscle strength in his lower legs.

The other patient was a 14-year-old girl who was also born into an unaffected family. At the age of five, she developed signs of ichthyosis, which spread all over her body and worsened with exposure to the sun. At 12, she could not stand on tiptoes, and by 14, had difficulty walking due to a loss of muscle tone. Doctors also found a decrease in the sensation of vibrations and pain in both feet.

Likewise, her cognitive tests were normal, while nerve conduction studies showed weak electrical signal strength in the peripheral nerves of the arms and legs. Ultrasound revealed nerve enlargement and mild fatty infiltration in the calf muscles. Routine blood tests were normal, including serine levels, but they also showed signs of malnutrition. Decreased myelinated nerve fiber density and evidence of axonal damage were also observed.

Like the boy, this patient carried the same c.43G>C variant in one of them PSAT1 copies genes, but unlike the boy, she had a c.112A>C variant in the second PSAT1 The copy of the gene (A stands for adenine, another building block of DNA). Her mother was an unaffected carrier of the c.43G>C variant, and her father of c.112A>C.

She was also given serine supplements, which significantly alleviated her ichthyosis after 10 days of treatment. After 10 months, strength in all of her muscles appeared to be normal, even though her serine levels were elevated due to the treatment.

Serine supplementation was well tolerated in both patients.

The researchers recommended testing for serine, assessments of skin, sensory, and motor function, monitoring for side effects, and exploration of serine doses.

Disease-causing PSAT1 The scientists concluded that the variants can cause axonal CMT disease, which progressively affects the motor and sensory nerves of the peripheral nervous system. This is the first report on PSAT1Axon-related CMT without CNS-related abnormalities, expanding the clinical and genetic range of PSAT1Associated diseases.

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