5,10-Methenyltetrahydrofolate synthetase deficiency (MTHFS deficiency) is a rare

neurodevelopmental disorder Neurodevelopmental disorders are a group of mental conditions negatively affecting the development of the nervous system, which includes the brain and spinal cord. According to the American Psychiatric Association Diagnostic and Statistical Manu ...

caused by

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s affecting the

MTHFS In enzymology, a 5-formyltetrahydrofolate cyclo-ligase () is an enzyme that catalyzes the chemical reaction :ATP + 5-formyltetrahydrofolate (folinic acid) \rightleftharpoons ADP + phosphate + 5,10-methenyltetrahydrofolate Thus, the two subs ...

gene, which encodes the enzyme 5,10-Methenyltetrahydrofolate synthetase. The disease starts at birth or in early infancy and presents with

microcephaly Microcephaly (from Neo-Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it m ...

short stature Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ...

, and developmental delay. Patients develop

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s that may be hard to control.

Brain imaging Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Incre ...

shows delayed

myelin Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

ation and hypomyelination.

Mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s of the

gene disrupt

folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

metabolism, which is very important for the proper development of the

nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...

and

ation of

nerve fibers A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the electrochemical nerve impulses called ...

. Patients present with

cerebral folate deficiency Cerebral may refer to: * Of or relating to the brain * Cerebrum, the largest and uppermost part of the brain * Cerebral cortex, the outer layer of the cerebrum * Retroflex consonant, also referred to as a cerebral consonant, a type of consonant so ...

, a condition in which there are reduced levels of

5-MTHF Levomefolic acid ( INN, also known as L-5-MTHF, L-methylfolate and L-5-methyltetrahydrofolate and (6''S'')-5-methyltetrahydrofolate, and (6''S'')-5-MTHF) is the primary biologically active form of folate used at the cellular level for DNA reprodu ...

in the

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...

. However, contrary to other causes of

, the use of

folinic acid Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to ...

for treatment may be contraindicated due to excess levels of

in the organism of patients. The first case report of MTHFS deficiency was published in 2018.

References

{{Reflist Neurodevelopmental disorders

See also

References