Conditions Overview

Amino Acidopathies & Organic Acidemia

Name	Symptoms
Propionic aciduria	Poor feeding, vomiting, weak muscle tone (hypotonia), and lethargy. May progress to more serious medical problems, including heart abnormalities, seizures, coma, and possibly death.
Holocarboxylase synthetase deficiency	Poor feeding, lethargy, behavior changes, weak muscle tone (hypotonia), and severe eczema. Untreated children can develop skin rashes, hair loss (alopecia), vision/hearing loss, failure to thrive, developmental delays, abnormal tensing of the muscles (spasticity), difficulty with balance and coordination (ataxia), seizures, and death.
Methylmalonic aciduria (Cbl C and Cbl D)	Acute neurological deterioration, retinal deterioration, small head size (microcephaly), severe brain abnormalities, severe learning difficulties, behavioral problems and movement, and deviation from normal walking (gait abnormalities).
Methylmalonic Aciduria	Excessive acid in the body (metabolic acidosis), dehydration, excess of ammonia in the blood (hyperammonemia), present of ketone bodies in the urine (ketonuria), vomiting, low levels of blood sugar (hypoglycemia), and failure to thrive.
Methylmalonic aciduria (Cbl A and Cbl B)	Excessive acid in the body (metabolic acidosis), dehydration, excess of ammonia in the blood (hyperammonemia), present of ketone bodies in the urine (ketonuria), vomiting, low levels of blood sugar (hypoglycemia), and failure to thrive.
Malonic aciduria	Developmental delays, weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low levels of blood sugar (hypoglycemia).
Isobutyryl-CoA dehydrogenase deficiency	Weakened and enlarged heart (dilated cardiomyopathy), weak muscle tone (hypotonia), and developmental delays.
2-methylbutyryl-CoA dehydrogenase deficiency	Poor feeding, lethargy, vomiting, and an irritable mood. May progress to serious medical problems such as difficulty breathing, seizures, and coma.
Methylmalonic Semialdehyde Dehydrogenase Deficiency	Developmental delays.
Beta-ketothiolase deficiency	Vomiting, dehydration, difficulty breathing, lethargy, and seizures.
Isovaleric aciduria	Poor feeding, vomiting, seizures, and lethargy. May progress to more serious medical problems, including seizures, coma, and possibly death.
3-Methylcrotonylglycinuria	Poor feeding, recurrent episodes of vomiting and diarrhea, lethargy, and weak muscle tone (hypotonia). If untreated, this disorder can lead to developmental delays, seizures, and coma.
3-Methylglutaconic aciduria (type I - hydratase deficiency)	Speech delay, psychomotor delay, excessive acid in the body (metabolic acidosis), abnormal muscle tone, and one of the most severe forms of cerebral palsy (spactic quadriparesis).
Barth Syndrome	Weakened and enlarged heart (dilated cardiomyopathy), neutropenia, skeletal muscle weakmess, and developmental delays.
3-hydroxy 3-methyl glutaric aciduria	Vomiting, diarrhea, dehydration, lethargy, and weak muscle tone (hypotonia). If untreated, the disorder can lead to breathing problems, convulsions, coma, and death.
Glutaric aciduria type II	Poor feeding, vomitting, and possible death. Severe cases can cause brain malformations, an enlarged liver, Weakened and enlarged heart (dilated cardiomyopathy), malformations of the kidneys, unusual facial features, and genital abnormalities.
Glutaric aciduria type I	Unusually large heads (macrocephaly), spasms, and decreased muscle tone.
Mevalonate kinase deficiency	Developmental delays, progressive difficulty with balance and coordination (ataxia), progressive problems with vision, and failure to thrive. Typically have an unusually small, elongated head
Glyceroluria	Developmental delays.
Phenylketonuria (phenylalanine hydroxylase deficiency)	Permanent intellectual disability, seizures, developmental delays, behavioral problems, and psychiatric disorders
Hyperphenylalaninemia (variant, benign)	Increased risk of developing brain damage.
2-Methyl 3-hydroxy butyric aciduria	Excessive acid in the body (metabolic acidosis), low levels of blood sugar (hypoglycemia), weak muscle tone (hypotonia), seizures, movement problems, retinal degeneration, and hearing loss.
Tyrosinemia type I (hepatorenal tyrosinemia)	Failure to thrive, diarrhea, vomiting, jaundice, cabbage-like odor, and increased tendency to bleed (particularly nosebleeds). May also lead to liver and kidney failure, problems affecting the nervous system, and an increased risk of liver cancer.
Tyrosinemia type II (oculocutaneous tyrosinemia)	Excessive tearing, abnormal sensitivity to light, eye pain and redness, and painful skin lesions on the palms and soles. May also have some degree of intellectual disability.
Tyrosinemia type III (4-hydroxyphenylpyruvate dioxygenase def.)	Intellectual disability, seizures, and periodic loss of balance and coordination (intermittent ataxia).
Transient tyrosinemia of the newborn	Prolonged jaundice, lethargy
Tyrosinemia caused by a liver disease	Liver dysfunction, and prolonged jaundice.
Maple syrup urine disease	Poor feeding, vomiting, lethargy, and developmental delays. If untreated, may lead to seizures, coma, and death.
N-acetylglutamate synthase deficiency	Lethargic, poor feeding, and a poorly controlled breathing rate or body temperature. May also experience seizures, unusual body movements, and go into coma.
Carbamylphosphate synthetase deficiency	Unusual sleepiness, a poorly controlled breathing rate or body temperature, unwillingness to feed, vomiting after feeding, unusual body movements, seizures, and coma.
Ornithine transcarbamylase deficiency	Lethargic, poor feeding, and a poorly controlled breathing rate or body temperature. May also experience seizures, unusual body movements, and go into coma.
Citrullinemia (argninosuccinate synthase deficiency)	Lethargy, poor feeding, vomiting, seizures, and loss of consciousness. Life-threatening in many cases.
Citrullinemia type II (citrin deficiency)	Causing confusion, restlessness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma.
Argininosuccinic acidemia	Lethargic, poor feeding, and a poorly controlled breathing rate or body temperature. May also experience seizures, unusual body movements, and go into coma.
Argininuria	Stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity), developmental delays, intellectual disability, seizures, tremor, and difficulty with balance and coordination (ataxia).
Hypermethioninuria (MAT I/III deficiency)	Intellectual disability, neurological problems, delays in motor skills such as standing or walking, sluggishness, muscle weakness, liver problems, and unusual facial features. Breath, sweat, or urine may have a smell resembling boiled cabbage.
Homocystinuria cystathionine beta-synthase deficiency	Myopia, increased risk of abnormal blood clotting, brittle bones that are prone to fracture (osteoporosis), and other skeletal abnormalities.
Alkaptonuria	Typically develop arthritis, particularly in the spine and large joints, beginning in early adulthood.
Tada syndrome	Dwarfism, mental defect, abnormal sensitivity to light, and deviation from normal walking (gait abnormalities).
Encephalopathy due to hydroxykynureninuria	Psychomotor retardation, nonprogressive brain disease, too much muscle tone (hypertonia), headaches, and stereotyped gestures.
Valinemia	Vomiting, failure to thrive, intellectual disability, and fatigue.
Hyperleucine-isoleucinemia	Seizures, failure to thrive, and intellectual disability.
Dihydrolipoyl dehydrogenase(E3) deficiency	Burnt sugar smell to urine and body, developmental delays, and weak muscle tone (hypotonia) during infancy.
Beta-hydroxyisobutyryl CoA deacylase deficiency	Unusual facial features, and multiple vertebral anomalies.
Histidinuria	Intellectual disability, behavioral problems, and learning disorders.
Hartnup syndrome	Increased sensitivity of the skin to sunlight, difficulty with balance and coordination (ataxia), abnormal tensing of the muscles (spasticity), delayed motor development, trembling, headaches, weak muscle tone (hypotonia), anxiety, emotional instability, delusions, hallucinations, and abnormal amount of amino acids in the urine (aminoaciduria).
Lysinuric protein intolerance	An enlarged liver and spleen (hepatosplenomegaly), short stature, muscle weakness, impaired immune function, and progressively brittle bones that are prone to fracture (osteoporosis). May interfere with lung function and can be life-threatening.
Alpha-ketoadipic aciduria	Psychomotorically retarded.
Saccharopinuria	Intellectual disability, behavioral problems, unusual facial feature, and short stature.
Seizures-intellectual deficit due to hydroxylysinuria	Seizures, and intellectual disability.
Cystathioninuria	Intellectual disability.
Hyperprolinemia type I	Seizures, intellectual disability, and other neurological or psychiatric problems.
Hyperprolinemia type II	Seizures, and intellectual disability.
Hyper hydroxyprolinemia	Intellectual disability.
2-hydroxyglutaric aciduria	Severe seizures, weak muscle tone (hypotonia), and breathing and feeding problems. Usually survive only into infancy or early childhood.
Hawkinsinuria	Failure to thrive, persistent excessive acid in the body (metabolic acidosis), and fine and sparse hair.
Biotinidase deficiency	Seizures, weak muscle tone (hypotonia), breathing problems, and developmental delays. If left untreated, the disorder can lead to hearing loss, eye abnormalities and loss of vision, difficulty with balance and coordination (ataxia), skin rashes, hair loss (alopecia), and a fungal infection called candidiasis.
Fumarate hydratase deficiency	Poor feeding, failure to thrive, weak muscle tone (hypotonia), lethargy, and seizures. Most affected individuals are non-verbal and non-ambulatory, and many die during early childhood.
Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome	Poor feeding, vomiting, lethargy, low temperature, and rapid breathing

Disorders of Sugar Metabolism

Name	Symptoms
Classic galactosemia	Poor feeding, lethargy, failure to thrive, jaundice, liver damage, and bleeding.
Galactokinase deficiency	Cataracts, and liver damage
Galactose epimerase deficiency	Cataracts, developmental delays, intellectual disability, liver disease, and kidney problems.
Transient galactosemia	Abnormal liver functions, and failure to thrive.
D-glyceric aciduria	Brain disease, chronic persistent excessive acid in the body (metabolic acidosis), seizures, severe intellectual disability, small head size (microcephaly), and speech delay.
Fructose-1, 6-Diphosphatase Deficiency	Low levels of blood sugar (hypoglycemia), life-threatening buildup of lactic acid (lactic acidosis), present of ketone bodies in the urine (ketonuria), hyperventilation, convulsions, coma, and mild enlarged liver (hepatomegaly).
Endogenous sucrosuria	Intellectual disability.
Lactose intolerance	Severe diarrhea, severe dehydration, and weight loss.

Disorders of Fatty Acid Metabolism

Name	Symptoms
Short-chain acyl-CoA dehydrogenase deficiency	Vomiting, low levels of blood sugar (hypoglycemia), lethargy, and failure to thrive.
Medium-chain acyl-CoA dehydrogenase deficiency	Vomiting, lethargy, and low levels of blood sugar (hypoglycemia). At risk for serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden death.
Medium/short-chain L-3-OH acyl-CoA DH deficiency	Poor appetite, vomiting, diarrhea, lethargy, weak muscle tone (hypotonia), liver problems, low levels of blood sugar (hypoglycemia), and abnormally high levels of insulin (hyperinsulinism). At risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden death.
Long-chain 3-OH acyl-CoA dehydrogenase deficiency	Feeding difficulties, muscle weakness (hypotonia), low levels of blood sugar (hypoglycemia), muscle pain, and breakdown of muscle tissue. At risk for serious heart problems, breathing difficulties, coma, and sudden death.
Ethylmalonic encephalopathy	Progressively developmental delays, weak muscle tone (hypotonia), seizures, and abnormal movements.
Dicarboxylic aciduria	Low levels of blood sugar (hypoglycemia).

Peroxisomal Diseases

Name	Symptoms
Zellweger syndrome	Weak muscle tone (hypotonia), feeding problems, hearing loss, vision loss, and seizures. Affected individuals have distinctive facial features, including a flattened face, broad nasal bridge, and high forehead, and typically do not survive beyond the first year of life.
Neonatal adrenoleukodystrophy	Weak muscle tone (hypotonia), vision problems, hearing loss, liver dysfunction, developmental delays, and some degree of intellectual disability.
Infantile Refsum disease	Weak muscle tone (hypotonia), vision problems, hearing loss, liver dysfunction, developmental delay, and some degree of intellectual disability.
Zellweger-like syndrome	Distinctive facial features, including a flattened face, broad nasal bridge, and high forehead, profound weak muscle tone (hypotonia), intellectual deficit, and metabolic anomalies.
Primary Hyperoxaluria	Failure to thrive, elevated calcium levels in the body (nephrocalcinosis), decrease number of red blood cells (anemia), and persistent excessive acid in the body (metabolic acidosis).

Disorders of Purine, Pyrimidine Metabolism

Name	Symptoms
Adenosine deaminase deficiency	Pneumonia, chronic diarrhea, widespread skin rashes and developmental delays. Without treatment, these babies usually do not survive past age 2.
Lesch-Nyhan syndrome	Abnormal involuntary muscle movements, such as tensing of various muscles (dystonia), jerking movements (chorea), and flailing of the limbs (ballismus), and self-injury (including biting and head banging).
Kelley-Seegmiller syndrome	Presence of orange crystals in diapers. Urinary infections, and renal obstruction. Gout may appear after puberty.
Adenine phosphoribosyltransferase deficiency	Recurrent kidney stones and urinary tract stones.
Hereditary xanthinuria	Urinary tract infection, presence of red blood cells in the urine (hematuria), kidney stones, acute renal failure, crystals in urine (crystalluria), and urinary tract stones.
Orotic aciduria	Physical and intellectual disability.
Dihydropyrimidine dehydrogenase deficiency	Recurrent seizures (epilepsy), intellectual disability, small head size (microcephaly), increased muscle tone (hypertonia), delayed development of motor skills such as walking, and autistic behaviors that affect communication and social interaction. Vulnerable to severe, potentially life-threatening toxic reactions to certain drugs called fluoropyrimidines that are used to treat cancer.
Dihydropyrimidinase deficiency	Neurologic abnormalities
Beta-ureidopropionase deficiency	Severe neurologic involvement with intellectual disability and seizures

Other IEMs

Name	Symptoms
Hyperglycinuria	Failure to thrive
Sarcosinuria	Intellectual disability, growth failure, enlarged liver (hepatomegaly), abnormal skull shape (craniosynostosis), conjoined fingers, and weakened and enlarged heart (dilated cardiomyopathy).
Imidazole aminoaciduria	Developmental delays.
Formiminoglutamic aciduria	Developmental delays.
Carnosinuria	Intellectual disability, seizures and congenital muscular disease.
Canavan disease	Problems with development, including a delay in motor skills such as turning over, controlling head movement, and sitting without support. Typically also have weak muscle tone (hypotonia), unusually large head size (macrocephaly), abnormal posture, intellectual disability, feeding and swallowing difficulties, seizures, and sleep disturbances.
Glutathione synthetase deficiency	Seizures, generalized slowing down of physical reactions, movements, and speech, intellectual disability, and a loss of coordination (ataxia).
Gamma-glutamyl transpeptidase deficiency	Abnormal breakdown of red blood cells.
Succinic semialdehyde dehydrogenase deficiency	Developmental delays, intellectual disability, and weak muscle tone (hypotonia).
Hyperpipecolatemia	Intellectual disability, weak muscle tone (hypotonia), and abnormalities in the brain structure (Joubert's syndrome).
Neonatal intrahepatic cholestasis caused by citrin deficiency	Liver dysfunction.
Beta-aminoisobutyric aciduria	Neurological impairment.

Lactic Acidemia & Hyperpyruvic Acidemia

Name	Symptoms
Pyruvate dehydrogenase e1-beta deficiency	Delayed development of mental abilities and motor abilities and other neurological problems such as intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination and difficulty walking. Potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat.
Pyruvate dehydrogenase phosphatase deficiency	Exercise intolerance, and mild developmental delays.
Pyruvate carboxylase deficiency	Developmental delays, and life-threatening buildup of lactic acid (lactic acidosis). Increased acidity in the blood can lead to vomiting, abdominal pain, fatigue, muscle weakness, and difficulty breathing.
Pyruvate decarboxylase deficiency	Life-threatening buildup of lactic acid (lactic acidosis), poor feeding, lethargy, developmental delays, weak muscle tone (hypotonia), seizures, difficulty with balance and coordination (ataxia), and tensing of various muscles (dystonia).
Leigh syndrome	Psychomotor regression. Typically results in death within a couple of years, usually due to respiratory failure.
Cytochrome c oxidase deficiency	Muscle weakness, weak muscle tone (hypotonia), severe brain dysfunction, heart disease, liver failure, life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea and an irregular heart rate.
De Toni-Debré-Fanconi syndrome	Polyuria (excessive urination), polydipsia (excessive thirst), enuresis (uncontrollable urination), vomitting, and seizures.

For more information about the conditions, please visit the following websites:

American College of Medical Genetics and Genomics (www.acmg.net)
Genetics Home Reference (ghr.nlm.nih.gov)
Online Mendelian Inheritance in Man (www.omim.org)
Orphanet (www.orpha.net)
PubMed (Pubmed.gov)

Conditions Overview

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