Organic Acidemias Health Article

Signs and symptoms

Symptoms of organic acidemias vary with type and sometimes even within a specific disorder. Isovaleric acidemia (IA) can present itself in two ways: acute severe or chronic intermittent. Roughly half of IA patients have the acute sever disorder and half the chronic intermittent type. In acute severe cases, patients are healthy at birth but show symptoms between one to 14 days later. These symptoms include vomiting, refusal to eat, dehydration, listlessness, and lethargy. Other symptoms can include shaking, twitching, convulsions, and low body temperature (under 97.8°F or 36.6°C), and a foul "sweaty feet" odor. If left untreated, the infant can lapse into a coma and die from severe ketoacidosis, hemorrhage, or infections. In the chronic intermittent type, symptoms usually occur within a year after birth and is usually preceded by upper respiratory infections or an increased consumption of protein-rich foods, such as meat and dairy products. Symptoms include vomiting, lethargy, "sweaty feet" odor, acidosis, and ketonuria. Additional symptoms may include diarrhea, thrombocytopenia, neutropenia, or pancytopenia.

There is a wide range of symptoms for 3-methylcrotonglycemia, which can occur in newborns, infants, and young children. These include irritability, drowsiness, unwillingness to eat, vomiting, and rapid breathing. Other symptoms can include hypoglycemia, alopecia, and involuntary body movements.

Approximately 30% of patients with hydroxymethylglutaric acidemia show symptoms within five days after birth and 60% between three and 24 months. Symptoms vary and can include vomiting, deficient muscle tone, lethargy, seizures, metabolic acidosis, hypoglycemia, and hyperammonemia.

Symptoms of methylmalonic acidemia (MA) due to methylmalonyl-CoA mutase (MCoAM) deficiency include lethargy, failure to thrive, vomiting, dehydration, trouble breathing, deficient muscle tone, and usually present themselves during infancy. MA due to N-methyltetrahydrofolate: homocysteine methyltransferase deficiency and high homocysteine levels usually occurs during the first two months after birth but has been reported in children as old as 14 years. General symptoms are the same as for MA due to MCoAM but can also include fatigue, delirium, dementia, spasms, and disorders of the spinal cord or bone marrow.

Symptoms of glutaric acidemia type I usually appear within two years after birth and generally become apparent when a minor infection is followed by deficient muscle tone, seizures, loss of head control, grimacing, and dystonia of the face, tongue, neck, back, arms, and hands. Glutaric acidemia type II symptoms fall into three categories:

• Infants with congenital anomalies present symptoms within the first 24 hours after birth, with symptoms of deficient muscle tone, severe hypoglycemia, hepatomegaly (enlarged liver), metabolic acidosis, and sometimes a "sweaty feet" odor. In some patients, signs include a high forehead, low-set ears, enlarged kidneys, excessive width between the eyes, a mid-face below normal size, and genital anomalies.
• Infants without congenital anomalies have signs of deficient muscle tone, tachypnea (increased breathing rate), metabolic acidosis, hepatomegaly, and a "sweaty feet" odor.
• Mild or later onset symptoms in children that include vomiting, hypoglycemia, hepatomegaly, and myopathy (a disorder of muscle or muscle tissue).

There are two types of propionic acidemia, one caused by propionyl-CoA carboxylase (PCoAC) deficiency and the other caused by multiple carboxylase (MC) deficiency. Symptoms of both disorders are generally the same and include vomiting, refusal to eat, lethargy, hypotonia, dehydration, and seizures. Other symptoms may include skin rash, ketoacidosis, irritability, metabolic acidosis, and a strong smelling urine commonly described as "tom cats"' urine.

There are five types of organic acidemias of fatty acid oxidation that involve deficiencies of acyl-CoA dehydrogenase enzymes: SCAD, MCAD, LCAD, VLCAD, and LCHAD. General symptoms for all five of these disorders include influenza-or cold-like symptoms, hyperammonemia, metabolic acidosis, hyperglycemia, vomiting, a "sweaty feet" odor, and delay in physical development. In young children, other symptoms can include loss of hair, involuntary or uncoordinated muscle movements (ataxia), and a scaly rash (seborrhea rash.) Symptoms generally appear between two months and two years of age, but can appear as early as two days after birth up to six years of age.

There are two combined carboxylase deficiency organic acidemias: holocarboxylase synthetase deficiency and biotindase deficiency. Symptoms of holocarboxylase deficiency include sleep and breathing difficulties, hypotonia, seizures, alopecia, developmental delay, skin rash, metabolic acidosis, ketolactic acidosis, organic aciduria, and hyperammonemia. Symptoms of biotindase deficiency include seizures, involuntary muscular movements, hypotonia, rapid breathing, developmental delay, hearing loss, and visual problems. Skin rash, alopecia, metabolic acidosis, organic acidemia, and hyper ammonemia can also occur.

Symptoms of beta-ketothiolase deficiency vary. In infants, the most common symptoms include severe metabolic acidosis, ketosis, vomiting, diarrhea (often bloody), and upper respiratory or gastrointestinal infections. Adults with the disorder are usually asymptomatic (showing no outward signs of the disease).