serine deficiency

Serine deficiency disorders are a group of rare, inherited metabolic disorders that affect the synthesis of the amino acid L-serine. These disorders are caused by defects in one of the three enzymes responsible for synthesizing L-serine.

Clinical Characteristics

• Severe neurological symptoms, including psychomotor retardation, microcephaly (small head size), and seizures in newborns and children
• Progressive polyneuropathy (nerve damage) in adult patients
• Spectrum of disease ranging from lethal prenatal-onset Neu-Laxova syndrome to serine deficiency with infantile, juvenile, or adult onset

Symptoms

• Intractable seizures
• Severe psychomotor retardation
• Microcephaly
• Milder forms of seizure disorders and mild mental retardation in adolescents and adults
• Progressive polyneuropathy in adult patients

Causes

• Defects in the biosynthesis of L-serine, caused by mutations in one of the three synthesizing enzymes.

According to

Serine deficiency, also known as serine-deficiency syndrome, is a rare inherited metabolic disorder that affects normal growth and development, particularly in the central nervous system.

Common signs and symptoms of serine deficiency include:

• Severe neurological symptoms such as microcephaly (small head size) [1]
• Psychomotor retardation (delayed or impaired mental and physical development) [2][3]
• Seizures [4]
• Progressive polyneuropathy (a condition that affects the nerves, leading to muscle weakness and wasting) [5]

In infants and young children, serine deficiency can also cause:

• Microcephaly
• Psychomotor retardation

As individuals with serine deficiency grow older, they may experience additional symptoms such as:

• Cognitive issues, including memory loss or difficulty concentrating [8]
• Mood swings
• Weakened immune response

It's essential to note that these symptoms can vary in severity and presentation from one individual to another. If you suspect a case of serine deficiency, it is crucial to consult with a qualified healthcare professional for proper diagnosis and treatment.

References: [1] Context result 4 [2] Context result 2 [3] Context result 7 [5] Context result 3 [8] Context result 8

Serine deficiency disorders can be diagnosed through various diagnostic tests, which are essential for establishing an accurate diagnosis and developing a treatment plan.

• Measuring Serine Levels: Confirmation of the diagnosis of serine deficiency can be made by measuring serine levels in plasma and cerebrospinal fluid (CSF) [4]. This test is crucial in identifying individuals with serine deficiency disorders.
• Amino Acid Analysis: Analyzing amino acids in plasma and CSF can also diagnose all serine deficiency disorders, but it's essential to be aware of the importance of age-related reference values [5].
• Genetic Testing: While genetic tests are not specifically mentioned for serine deficiency, they may be used to identify genetic variants associated with this condition. However, these tests should not be used as a standalone diagnostic tool and should only be performed under medical supervision.
• Biochemical Abnormalities: Serine deficiency disorders are characterized by specific biochemical abnormalities, including elevated amino acid concentrations in plasma and CSF [8]. These abnormalities can be detected through various laboratory tests.

It's essential to note that serine deficiency disorders may be underdiagnosed due to the focus on detecting elevated amino acid concentrations rather than decreased values [3].

References: [1] - Not applicable [2] - Not applicable [3] (Context 3) [4] (Context 4) [5] (Context 5) [8] (Context 8)

Serine deficiency disorders are potentially treatable conditions, and treatment typically involves administering L-serine, either alone or in combination with glycine.

• The current practice of amino acid treatment with L-serine and glycine in serine deficiency is reviewed in [1] (TJ de Koning · 2006 · Cited by 86).
• Studies have shown that l-Serine treatment can lead to a significant reduction of seizures after one week of treatment and decrease of electroencephalographic abnormalities, as reported in [2] (by A Brassier · 2016 · Cited by 46).
• All patients with serine deficiency, regardless of age of presentation and the underlying molecular defect, will benefit from L-serine therapy, which has been found to be effective in improving seizure control and overall well-being, as stated in [4].
• The outcome of treatment with oral serine ranges from improvement of seizure control and well being in older children to normal psychomotor (mental and physical) development, as reported in [6].

The dosing parameters for L-serine therapy are not explicitly mentioned in the search results. However, it is suggested that prompt recognition and treatment are crucial for optimal outcomes, as stated in [7].

Differential Diagnosis of Serine Deficiency

Serine deficiency disorders are a group of rare genetic conditions characterized by impaired synthesis of the amino acid serine, leading to various neurological and developmental symptoms.

Key Features:

• Classic Menkes disease: Infants with classic Menkes disease appear healthy until age 1.5-3 months, when loss of developmental milestones, hypotonia, seizures, and poor weight gain occur [2].
• Neurological phenotype: Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly, and seizures in newborns and infants [3].
• Progressive polyneuropathy: In adolescents and adults, serine deficiency can cause progressive polyneuropathy and mild seizures with mental retardation [4].
• Infantile-onset serine deficiency: This form presents with seizures, microcephaly, developmental delay, intellectual disability, and spastic quadriplegia in infancy [5].

Differential Diagnosis:

The differential diagnosis of serine deficiency disorders includes other conditions that present with similar symptoms, such as:

• ASCT1 transporter deficiency
• GOT2 deficiency
• Other selected disorders with clinical and/or biochemical features [1]

Important Considerations:

• Genetic testing: The diagnosis of a serine deficiency disorder is established in a proband with biallelic pathogenic variants in PHGDH, PSAT1, or PSPH identified [7].
• Differential diagnosis: Serine biosynthesis defects have to be considered in the differential diagnosis of patients with mental retardation, microcephaly, seizures, and on MRI abnormalities [8].

References:

[1] SN van der Crabben (2023) - Differential Diagnosis​​ ASCT1 transporter deficiency, GOT2 deficiency, and other selected disorders with clinical and/or biochemical features...

[2] Infants w/classic Menkes disease appear healthy until age 1.5-3 mos, when loss of developmental milestones, hypotonia, seizures, & poor weight gain occur.

[3] Mar 6, 2013 - Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly and seizures in newborns and ...

[4] Progressive polyneuropathy and mild seizures with mental retardation are distinct clinical phenotypes of serine deficiency in adolescents and adults, caused by ...

[5] Infantile-onset serine deficiency presents with seizures, microcephaly, developmental delay, intellectual disability, and spastic quadriplegia. Juvenile-onset ...

[7] The diagnosis of a serine deficiency disorder is established in a proband with biallelic pathogenic variants in PHGDH, PSAT1, or PSPH identified...

[8] Serine biosynthesis defects have to be considered in the differential diagnosis of patients with mental retardation, microcephaly, seizures, and on MRI abnormalities...