pattismith
Senior Member
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A very interesting paper (june 2015) that may be a guide for testing CFS/ME patients as well (keep in mind that congenital or post natal onset always leads to more severe clinical features than later in life onset, if we consider the metabolic diseases in this list that are susceptible to adult onset)
"ABSTRACT
....This paper provides an overview of these metabolic disorders in the context of ASD and discusses their characteristics, diagnostic testing, and treatment with concentration on mitochondrial disorders. To this end, this paper aims to help optimize the diagnosis and treatment of children with ASD and epilepsy."
....
Table 1. Metabolic disorders associated with epilepsy and autism spectrum disorder.
Disorder / Clinical features / Diagnostic testing
I-Disorders of energy metabolism
I.1-Mitochondrial diseases
Developmental regression, gross motor delay, fatigability, ataxia, and gastrointestinal abnormalities
• Fasting serum lactate, pyruvate, acylcarnitine, amino acids, and urine organic acids
I.2-Creatine metabolism disorders
Developmental regression, mental retardation, dyskinesia, and family history of x-linked mental retardation
• Magnetic resonance spectroscopy
• Urine and serum creatine and guanidinoacetic acid
II-Disorders of cholesterol metabolism
Smith–Lemli–Opitz syndrome Low birth weight, failure to thrive, poor feeding, eczema, and congenital structural abnormalities of the heart, gastrointestinal tract, genitalia, kidney, limbs, face, and brain
• Blood 7-dehydrocholesterol and cholesterol
• DHCR7 sequencing
III-Disorders of cofactor (vitamin) metabolism
III.1-Cerebral folate deficiency
Ataxia, pyramidal signs, acquired microcephaly, dyskinesias, and visual and hearing loss
• Folate receptor alpha autoantibody
• Cerebrospinal fluid 5-methyltetrahydrofolate
III.2-Pyridoxine-dependent and pyridoxine-responsive seizures
Mental retardation, breath-holding, aerophagia, and self-injurious behavior
• Pyridoxine trial
• Plasma and cerebrospinal fluid pipecolic acid
• Urine α-aminoadipic semialdehyde
• ALDH7A1 sequencing
III.3-Biotinidase deficiency
Developmental delays, seborrheic dermatitis, alopecia, feeding difficulties, vomiting, diarrhea, brain atrophy, and ataxia
• Biotinidase activity
• BTD gene sequencing
III.4-Carnitine biosynthesis deficiency
Nondysmorphic male–male siblings with autism spectrum disorder
• Plasma and/or urine 6-N-trimethyllysine, 3-hydroxy-6-N-trimethyllysine, and γ-butyrobetaine.
IV-Disorders of γ-aminobutyric acid metabolism
Succinic semialdehyde dehydrogenase deficiency
Global developmental delay, myoclonus, hallucinations, ataxia, choreoathetosis, and dystonia
• Urine gamma-hydroxybutyric acid
V-Disorders of pyrimidine and purine metabolism
V.1-Adenylosuccinate lyase deficiency
Global developmental delay, microcephaly, distinct facies, growth retardation, mental retardation, cerebellar vermis hypoplasia, brain atrophy, excessive laughter, and extreme happiness
• Urine and/or cerebrospinal fluid succinyladenosine
V.2-Nucleotidase-associated PDD Hyperactivity,
compulsiveness, speech abnormalities, ataxia, abnormal gait, and frequent infections
• Urine uridine
V.3-Hyperuricosuric
autism Altered sensory awareness, ataxia, and fine motor deficits
• 24-hour urine urate
V.4-Phosphoribosylpyrophosphate synthetase deficiency
Developmental delay and ataxia • Urine uric and orotic acids
• Complete blood count
VI-Disorders of amino acid metabolism
VI.1-Phenylketonuria
Global developmental delay, mental retardation, microcephaly, spasticity, ataxia, poor growth, poor skin pigmentation, and aggressive behavior
• Serum phenylalanine
VI.2-Branched-chain ketoacid dehydrogenase kinase deficiency
Intellectual disability and consanguinity
• Plasma and cerebrospinal fluid branched-chain amino acids
VI.3-Altered tryptophan metabolism
No specific features besides autism spectrum disorder
• Reduced cellular generation of nicotinamide adenine dinucleotide
VII-Urea cycle disorders
Urea cycle disorder
Protein intolerance, temperature instability, ataxia, episodic somnolence and lethargy, cyclic vomiting, and psychosis
• Plasma ammonia and amino acids
• Urinary orotic acid
http://www.sciencedirect.com/science/article/pii/S1525505014004120#t0005
"ABSTRACT
....This paper provides an overview of these metabolic disorders in the context of ASD and discusses their characteristics, diagnostic testing, and treatment with concentration on mitochondrial disorders. To this end, this paper aims to help optimize the diagnosis and treatment of children with ASD and epilepsy."
....
Table 1. Metabolic disorders associated with epilepsy and autism spectrum disorder.
Disorder / Clinical features / Diagnostic testing
I-Disorders of energy metabolism
I.1-Mitochondrial diseases
Developmental regression, gross motor delay, fatigability, ataxia, and gastrointestinal abnormalities
• Fasting serum lactate, pyruvate, acylcarnitine, amino acids, and urine organic acids
I.2-Creatine metabolism disorders
Developmental regression, mental retardation, dyskinesia, and family history of x-linked mental retardation
• Magnetic resonance spectroscopy
• Urine and serum creatine and guanidinoacetic acid
II-Disorders of cholesterol metabolism
Smith–Lemli–Opitz syndrome Low birth weight, failure to thrive, poor feeding, eczema, and congenital structural abnormalities of the heart, gastrointestinal tract, genitalia, kidney, limbs, face, and brain
• Blood 7-dehydrocholesterol and cholesterol
• DHCR7 sequencing
III-Disorders of cofactor (vitamin) metabolism
III.1-Cerebral folate deficiency
Ataxia, pyramidal signs, acquired microcephaly, dyskinesias, and visual and hearing loss
• Folate receptor alpha autoantibody
• Cerebrospinal fluid 5-methyltetrahydrofolate
III.2-Pyridoxine-dependent and pyridoxine-responsive seizures
Mental retardation, breath-holding, aerophagia, and self-injurious behavior
• Pyridoxine trial
• Plasma and cerebrospinal fluid pipecolic acid
• Urine α-aminoadipic semialdehyde
• ALDH7A1 sequencing
III.3-Biotinidase deficiency
Developmental delays, seborrheic dermatitis, alopecia, feeding difficulties, vomiting, diarrhea, brain atrophy, and ataxia
• Biotinidase activity
• BTD gene sequencing
III.4-Carnitine biosynthesis deficiency
Nondysmorphic male–male siblings with autism spectrum disorder
• Plasma and/or urine 6-N-trimethyllysine, 3-hydroxy-6-N-trimethyllysine, and γ-butyrobetaine.
IV-Disorders of γ-aminobutyric acid metabolism
Succinic semialdehyde dehydrogenase deficiency
Global developmental delay, myoclonus, hallucinations, ataxia, choreoathetosis, and dystonia
• Urine gamma-hydroxybutyric acid
V-Disorders of pyrimidine and purine metabolism
V.1-Adenylosuccinate lyase deficiency
Global developmental delay, microcephaly, distinct facies, growth retardation, mental retardation, cerebellar vermis hypoplasia, brain atrophy, excessive laughter, and extreme happiness
• Urine and/or cerebrospinal fluid succinyladenosine
V.2-Nucleotidase-associated PDD Hyperactivity,
compulsiveness, speech abnormalities, ataxia, abnormal gait, and frequent infections
• Urine uridine
V.3-Hyperuricosuric
autism Altered sensory awareness, ataxia, and fine motor deficits
• 24-hour urine urate
V.4-Phosphoribosylpyrophosphate synthetase deficiency
Developmental delay and ataxia • Urine uric and orotic acids
• Complete blood count
VI-Disorders of amino acid metabolism
VI.1-Phenylketonuria
Global developmental delay, mental retardation, microcephaly, spasticity, ataxia, poor growth, poor skin pigmentation, and aggressive behavior
• Serum phenylalanine
VI.2-Branched-chain ketoacid dehydrogenase kinase deficiency
Intellectual disability and consanguinity
• Plasma and cerebrospinal fluid branched-chain amino acids
VI.3-Altered tryptophan metabolism
No specific features besides autism spectrum disorder
• Reduced cellular generation of nicotinamide adenine dinucleotide
VII-Urea cycle disorders
Urea cycle disorder
Protein intolerance, temperature instability, ataxia, episodic somnolence and lethargy, cyclic vomiting, and psychosis
• Plasma ammonia and amino acids
• Urinary orotic acid
http://www.sciencedirect.com/science/article/pii/S1525505014004120#t0005