Table 2. [Genetic Disorders in the Differential Diagnosis of Serine Deficiency Disorders]. - GeneReviews®

Gene	Disorder	MOI	Clinical Characteristics	Laboratory Findings
SLC1A4	ASCT1 transporter deficiency (OMIM 616657)	AR	Considerable phenotypic overlap w/serine deficiency disorders. Assoc w/DD, microcephaly, spastic tetraplegia, & variable seizures (infantile form may or may not be assoc w/seizures ¹). Hypomyelination & thin corpus callosum on MRI	No associated biochemical abnormalities Note: As ASCT1 is the major transporter for L-serine in brain tissue, it is possible that a defect of ASCT1 leads to an intracellular deficiency of L-serine. ²
GOT2	GOT2 deficiency (OMIM 618721)	AR	Early-onset encephalopathy w/progressive microcephaly & early-onset seizures (seizures are pyridoxine & L-serine responsive). ³ Atrophy & white matter abnormalities w/thin corpus callosum on MRI	Inhibited synthesis of serine results in secondary serine deficiency. In addition, citrulline may be ↑ & ammonia & lactate are mildly ↑.
ATP7A	Menkes disease (See ATP7A-Related Copper Transport Disorders.)	XL	Infants w/classic Menkes disease appear healthy until age 1.5-3 mos, when loss of developmental milestones, hypotonia, seizures, & poor weight gain occur. Diagnosis is usually suspected when infants exhibit neurologic findings & characteristic hair changes. Cerebral & cerebellar atrophy w/ventriculomegaly, delayed myelination, & vascular tortuosity on brain MRI	Low plasma & CSF serine values were observed in multiple boys w/Menkes disease-related early-onset intractable seizures & severe hypotonia (mechanism of low serine in these boys is unknown). ²
~40 genes ⁴	Mitochondrial complex I deficiency (OMIM PS252010 & 500014)	Depends on genetic etiology	Severe DD & seizures	Severe secondary serine deficiency has been observed in persons w/mitochondrial complex 1 deficiency. ²

Gene

Disorder

MOI

Clinical Characteristics

Laboratory Findings

SLC1A4

ASCT1 transporter deficiency (OMIM 616657)

Considerable phenotypic overlap w/serine deficiency disorders. Assoc w/DD, microcephaly, spastic tetraplegia, & variable seizures (infantile form may or may not be assoc w/seizures ¹).
Hypomyelination & thin corpus callosum on MRI

No associated biochemical abnormalities
Note: As ASCT1 is the major transporter for L-serine in brain tissue, it is possible that a defect of ASCT1 leads to an intracellular deficiency of L-serine. ²

GOT2

GOT2 deficiency (OMIM 618721)

Early-onset encephalopathy w/progressive microcephaly & early-onset seizures (seizures are pyridoxine & L-serine responsive). ³
Atrophy & white matter abnormalities w/thin corpus callosum on MRI

Inhibited synthesis of serine results in secondary serine deficiency.
In addition, citrulline may be ↑ & ammonia & lactate are mildly ↑.

ATP7A

Menkes disease (See ATP7A-Related Copper Transport Disorders.)

Infants w/classic Menkes disease appear healthy until age 1.5-3 mos, when loss of developmental milestones, hypotonia, seizures, & poor weight gain occur. Diagnosis is usually suspected when infants exhibit neurologic findings & characteristic hair changes.
Cerebral & cerebellar atrophy w/ventriculomegaly, delayed myelination, & vascular tortuosity on brain MRI

Low plasma & CSF serine values were observed in multiple boys w/Menkes disease-related early-onset intractable seizures & severe hypotonia (mechanism of low serine in these boys is unknown). ²

~40 genes ⁴

Mitochondrial complex I deficiency (OMIM PS252010 & 500014)

Depends on genetic etiology

Severe DD & seizures

Severe secondary serine deficiency has been observed in persons w/mitochondrial complex 1 deficiency. ²

From: Serine Deficiency Disorders

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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