Огляд порушень обміну амінокислот і органічних кислот

Hyper-beta-alaninemia (237400*)

Beta-alanine-alpha-ketoglutarate aminotransferase

Biochemical profile: Elevated urinary beta-alanine, taurine, GABA, and beta-aminoisobutyrate

Clinical features: Seizures, somnolence, death

Treatment: Pyridoxine

Methylmalonate/malonate semialdehyde dehydrogenase deficiency with 3-amino and 3-hydroxy aciduria (236795*)

Methylmalonate/malonate semialdehyde dehydrogenase

Biochemical profile: Elevated 3-hydroxyisobutyrate 3-aminoisobutyrate, 3-hydroxypropionate beta-alanine, and 2-ethyl-3-hydroxypropionate

Clinical features: None to mild

Treatment: Not determined

Methylmalonic semialdehyde dehydrogenase deficiency with mild methylmalonic acidemia

Methylmalonic semialdehyde dehydrogenase (see also Branched-chain amino acid metabolism)

Biochemical profile: Moderately elevated urine methylmalonate

Clinical features: Developmental delay, seizures

Treatment: No effective treatment

Hyper-beta-aminoisobutyric aciduria (210100*)

D(R)-3-Aminoisobutyrate:pyruvate aminotransferase

Biochemical profile: Elevated beta-aminoisobutyric acid

Clinical features: Benign

Treatment: None needed

Pyridoxine dependency with seizures (266100*)

Not determined

Biochemical profile: Elevated cerebrospinal fluid glutamate

Clinical features: Seizure disorder refractory to conventional anticonvulsants, high-pitched cry, hypothermia, jitteriness, dystonia, hepatomegaly, hypotonia, dyspraxia, developmental delay

Treatment: Pyridoxine

GABA-transaminase deficiency (137150*)

4-Aminobutyrate-alpha-ketoglutarate aminotransferase

Biochemical profile: Elevated plasma and cerebrospinal fluid GABA and beta-alanine, elevated carnosine

Clinical features: Accelerated linear growth, seizures, cerebellar hypoplasia, psychomotor delay, leukodystrophy, burst suppression electroencephalographic pattern

Treatment: No known treatment

4-Hydroxybutyric aciduria (271980*)

Succinic semialdehyde dehydrogenase

Biochemical profile: Elevated urinary 4-hydroxybutyrate and glycine

Clinical features: Psychomotor retardation, speech delay, hypotonia

Treatment: Vigabatrin

Carnosinemia (212200*), homocarnosinosis (236130*), or both

Carnosinase

Biochemical profile: In carnosinemia phenotype, carnosinuria despite meat-free diet, elevated urine anserine after ingestion of food containing imidazole dipeptides, normal cerebrospinal fluid

In homocarnosinosis phenotype, elevated cerebrospinal fluid homocarnosine, normal serum carnosine

Clinical features: Usually benign; reported symptoms probably due to ascertainment bias

Treatment: None needed

Gamma-glutamylcysteine synthetase deficiency (230450*)

Gamma-glutamylcysteine synthetase

Biochemical profile: Aminoaciduria, glutathione deficiency

Clinical features: Hemolysis, spinocerebellar degeneration, peripheral neuropathy, myopathy

Treatment: No clear treatment; avoidance of medications that trigger hemolytic crisis in G6PD deficiency

Pyroglutamic aciduria (5-oxoprolinuria; 266130*, 231900*)

Glutathione synthetase

Biochemical profile: Elevated urinary, plasma, and cerebrospinal fluid 5-oxoproline; increased gamma-glutamylcysteine; decreased glutathione level

Clinical features: Hemolysis, ataxia, seizures, intellectual disability, spasticity, metabolic acidosis

In mild form, no evidence of neurologic damage

Treatment: Sodium bicarbonate or citrate, vitamins E and C, avoidance of medications that trigger hemolytic crisis in G6PD deficiency

Gamma-glutamyltranspeptidase deficiency (glutathionuria; 231950*)

Gamma-glutamyltranspeptidase

Biochemical profile: Elevated plasma and urinary glutathione

Clinical features: Intellectual disability

Treatment: No specific treatment

5-Oxoprolinase deficiency (260005*)

5-Oxoprolinase

Biochemical profile: Elevated urinary 5-oxoproline

Clinical features: Probably benign

Treatment: None needed

Nonketotic hyperglycinemia (605899*)

Glycine cleavage enzyme system

Biochemical profile: Elevated plasma and cerebrospinal fluid glycine

Clinical features: In fetuses, severe hiccups

In neonatal form, severe hiccups, hypotonia, seizures, myoclonus, apnea, death

In infantile and episodic forms, seizures, intellectual disability, episodic delirium, chorea, vertical gaze palsy

In late-onset form, progressive spastic diplegia, optic atrophy, but no cognitive impairment or seizures

Treatment: No effective treatment; in some patients, temporary benefit from sodium benzoate and dextromethorphan

In some patients with specific mutations, benefit from cofactor therapy with pyridoxine (GLDC mutations) or folinic acid (AMT mutations)

P protein

H protein

T protein

L protein

Histidinemia (235800*)

Histidine ammonia-lyase

Biochemical profile: Elevated plasma histidine

Clinical features: Frequently benign; neurologic manifestations in some patients

Treatment: Low-protein diet

For symptomatic patients only, controlled histidine intake

Urocanic aciduria (276880*)

Urocanase

Biochemical profile: Elevated urine urocanic acid

Clinical features: Possible mild intellectual disability, mild ataxia, nystagmus, and tremor

Treatment: None needed

Hyperlysinemia (238700*)

Lysine:alpha-ketoglutarate reductase

Biochemical profile: Hyperlysinemia

Clinical features: Muscle weakness, seizures, mild anemia, intellectual disability, joint and muscular laxity, ectopia lentis; sometimes benign

Treatment: Limited lysine intake

2-Ketoadipic acidemia (245130*)

2-Ketoadipic dehydrogenase

Biochemical profile: Elevated urine 2-ketoadipate, 2-aminoadipate, and 2-hydroxyadipate

Clinical features: Benign

Treatment: None needed

Glutaric acidemia type I (231670*)

Glutaryl CoA dehydrogenase

Biochemical profile: Elevated urinary glutaric acid and 2-hydroxyglytaric acid

Clinical features: Dystonia, dyskinesia, degeneration of the caudate and putamen, frontotemporal atrophy, arachnoid cysts

Treatment: Aggressive treatment of intercurrent illness, carnitine

Protein, lysine, and tryptophan restriction

Saccharopinuria (268700*)

Alpha-aminoadipic semialdehyde-glutamate reductase

Biochemical profile: Elevated urine lysine, citrulline, histidine, and saccharopine

Clinical features: Intellectual disability, spastic diplegia, short stature, electroencephalographic abnormality

Treatment: No clear treatment

Hyperprolinemia, type I (239500*)

Proline oxidase (proline dehydrogenase)

Biochemical profile: Elevated plasma proline and urinary proline, hydroxyproline, and glycine

Clinical features: Usually benign; hereditary nephritis, nerve deafness

Treatment: None needed

Hyperprolinemia, type II (239510*)

Delta1-pyrroline-5-carboxylate dehydrogenase

Biochemical profile: Elevated plasma proline and pyrroline-5-carboxylate (P5C); elevated urinary P5C, delta1-pyrroline-5-carboxylate, proline, hydroxyproline, and glycine

Clinical features: During childhood, seizures, intellectual disability

During adulthood, benign

Treatment: None needed

Delta1-pyrroline-5-carboxylate synthetase deficiency (138250*)

Delta1-pyrroline-5-carboxylate synthetase

Biochemical profile: Low plasma proline, citrulline, arginine, and ornithine

Clinical features: Hyperammonemia, cataracts, intellectual disability, joint laxity

Treatment: Avoidance of fasting

Hyperhydroxyprolinemia (237000*)

4-Hydroxyproline oxidase

Biochemical profile: Hydroxyprolinemia

Clinical features: Disease association not proven

Treatment: None needed

Prolidase deficiency (170100*)

Prolidase

Biochemical profile: Amino acid profile normal in unhydrolyzed urine, but excessive proline and hydroxyproline in acid-hydrolyzed urine

Clinical features: Skin ulcers, frequent infections, dysmorphic features, immunodeficiency, intellectual disability, chronic lung disease

Treatment: Proline supplement, Mn++ and ascorbic acid, essential amino acids, blood transfusion (packed red blood cells), topical proline and glycine ointment

Sarcosinemia (268900*)

Sarcosine dehydrogenase

Biochemical profile: Elevated plasma sarcosine

Clinical features: Benign; intellectual disability reported

Treatment: None needed

D-glyceric aciduria (220120*)

D-glycerate kinase

Biochemical profile: Elevated urinary D-glyceric acid

Clinical features: Chronic acidosis, hypotonia, seizures, intellectual disability

Treatment: Bicarbonate or citrate for acidosis

Hartnup disease (234500*)

System B(0) neutral amino acid transporter

Biochemical profile: Neutral aminoaciduria

Clinical features: Atrophic glossitis, photodermatitis, intermittent ataxia, hypertonia, seizures, psychosis

Treatment: Nicotinamide

Cystinuria (220100*)

Renal dibasic amino acid transporter

Biochemical profile: Elevated urinary cystine, lysine, arginine, and ornithine

Clinical features: Nephrolithiasis, increased risk of impaired cerebral function

Treatment: Maintenance of fluid intake, bicarbonate or citrate, penicillamine or mercaptopropionylglycine

Type I

Heavy subunit

Types II and III

Light subunit

Iminoglycinuria (242600*)

Renal transporter of proline, hydroxyproline, and glycine

Biochemical profile: Elevated urinary proline, hydroxyproline, and glycine but normal plasma levels

Clinical features: Probably benign

Treatment: None needed

Guanidinoacetate methyltransferase deficiency (601240*)

Guanidinoacetate methyltransferase

Biochemical profile: Elevated guanidinoacetate, decreased creatine and phosphocreatine

Clinical features: Developmental delay, hypotonia, extrapyramidal movements, seizures, autistic behavior

Treatment: Creatine supplementation

Cystinosis

See table Lysosomal Transport Defects

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