Tandem Mass Spectrometry Disease Testing

Detectable disorders include metabolic disorders, hematologic disorders, and endocrinopathies. These three groups of disorders account for approximately 3,000 new cases of potentially fatal or debilitating disease each year for which outcomes are improved with early identification and treatment through newborn screening systems.

57 Diseases

Compiled by: Connor Gerhart

Disease: Argininemia
Metabolite: Cit and Arg
Incidence: 1 in 300,000- 1 in 1,000,000
Symptoms: Muscle stiffness, developmental delay and mental retardation.
Treatment: A low protein diet to prevent arginine and ammonia build up and there are medications that help the body get rid of excess arginine and ammonia
Age of Onset: 2 months- 4 years old
Animal Equivalents: Afects the final stage in the urea cycle in the liver so therefore all mammals are potential victims of Argininemia…(ureatelic animals(animals with the urea cycle)
Metabolite Concentration
Level Range:
Arginine and citrulline elevated. Arg - 152-1756uM
Prognosis: Good prognosis if disorder is treated prospectively from birth, progressive neurological manifestations if untreated
Metabolite + Missing or Ineffective
Enzyme —> Result:
Arginine + arginase enzyme —> ammonium, arginine, citrulline, lysine, and ornithine levels rise


(Arginine)

 
Disease: Argininosuccinic Aciduria (ASA)
Metabolite: Cit
Incidence: 1 in 70,000
Symptoms: Lack of appetite, vomiting, listlessness, seizures, and coma
Treatment: Treatment may include a high-caloric, protein-restrictive diet, arginine supplementation, administration of sodium benzoate and sodium phenylacetate. It may be necessary to prescribe dialysis in some cases.
Age of Onset: Disease is present at birth but symptoms aren’t present until days or weeks after birth
Animal Equivalents: Potentially all Mammals
Metabolite Concentration
Level Range:
Patient has condition if Cit <51 μmol/L
Prognosis: Natural History without Treatment: Mental and physical retardation due to hyperammonemia, cylic vomiting, seizures, cerebal edema and trichorrhexis nodosa. Coma and death possible.

Natural History with Treatment: Normal mental and physical development is possible if treatment is initiated before hyperammonemic crisis.
Metabolite + Missing or
Ineffective Enzyme —> Result:
Argininosuccinate+ Argininosuccinase —> ammonia, citrulline, glutamine, and urine argininosuccinic acid buildup


(Arginine)

 
Disease: Carbamoyl Phosphate Synthetase I Deficiency (CPS1)
Metabolite: Nitric Oxide (NO)
Incidence: 1 in 800,000
Symptoms: Lethargic, unwilling to eat, loss of breathing rate control, high body temperature, seizures (and possible coma), and possible developmental delay and intellectual disability.
Treatment: Valine, leucine, isoleucine, methionine and phenylalanine supplements
Age of Onset: Days from Birth
Animal Equivalents: Human, Rat, and Rabbit
Metabolite Concentration
Level Range:
Patient has condition if Nitric Oxide 14.0 micromol/L higher than normal 8.5 micromol/L lower than normal
Prognosis: 100% mortality if untreated, there is a direct correlation between the duration of hyper-ammonemic coma and morbidity (mental retardation, developmental delays, cortical atrophy), and good prognosis if disorder is treated prospectively from birth
Metabolite + Missing or Ineffective
Enzyme —> Result:
NH=O+
 
Disease: Citrullinemia (Type I and Type II)
Metabolite: Cit
Incidence: 1 in 100,000
Symptoms: Increased blood ammonia level (type I), Poor appetite (type I), Listlessness (type I), Vomiting (type I), Seizures (type II), Lack of argininosuccinate in blood (type I), Increased blood levels of citrulline (type I), Increased levels of ammonia in body tissues (type I), Increased citrulline levels (type I and II), Confusion (type II), Memory loss (type II), Restlessness (type II), Abnormal behaviors (type II), Irritability (type II), Hyperactivity (type II), Aggression (type II), Impaired vision (late onset form), Severe headache (late onset form), Balance problems (late onset form), Incoordination (late onset form) , Reduced energy (late onset form)
Treatment: Having a low-protein diet and/or special medical foods and formula is necessary to keeping the ammonia levels down. There are medications that are taken by mouth or by tube feeding to prevent high ammonia levels. There are also medications to help remove existing ammonia in the body. Dialysis is an example of a medication that helps remove ammonia from the blood. Also, an amino acid called arginine is often given by mouth to help prevent ammonia build-up.
Age of Onset: Less than 30 days old
Metabolite Concentration
Level Range:
Patient has condition if Cit >51 μmol/L
Prognosis: Timely diagnosis and treatment usually results in a good prognosis with normal growth and learning abilities - treatment is lifelong. In some severe cases, high ammonia levels can cause complications even with treatment.
Metabolite + Missing or Ineffective
Enzyme —> Result:
Citrulline + argininosuccinic acid synthetase › Citrulline and ammonia levels increase
 
Disease: Homocystinuria (Cystathione Synthase Deficiency)
Metabolite: Met
Incidence: 1 in 82,000
Symptoms: Symptoms include mental retardation, seizures, psychiatric disturbances, delays in reaching developmental milestones (e.g., crawling, walking, sitting), displacement of the lens of the eye (ectopia lentis), abnormal thinning and weakness of the bones (osteoporosis and scoliosis ), and/or the formation of blood clots (thrombi) in various veins and arteries that may lead to life-threatening complications.
Treatment: Homocystinuria is treated initially by changing the baby to a formula that does not contain methionine. Treatment may also include a methionine-restricted and cystine-supplemented diet, as well as large doses of Vitamin B6.
Metabolite Concentration Level Range: Patient has condition if Met < 96
Age of Onset: 3-4 years old
Prognosis: Although no cure exists for homocystinuria, vitamin B6 therapy can help about half of people affected by the condition. If the diagnosis is made while a patient is young, starting a low methionine diet quickly can prevent some mental retardation and other complications of the disease. For this reason, some states screen for homocystinuria in all newborns.Patients with persistent rises in blood homocysteine levels are at increased risk for blood clots. Clots can cause significant medical problems and shorten lifespan.
 
Disease: Hypermethioninemia
Metabolite: Met
Incidence: 1 in 60,000
Symptoms: There are usually no visible symptoms
Treatment: Prescribe intense methionine supplements; increase the levels of Vitamin B6 in diet, while decreasing the levels of protein in one’s diet.
Age of Onset: The metabolic disorder is present at birth but symptoms usually arrive later in childhood.
Metabolite Concentration
Level Range:
Patient has condition if Condition when Met >960
Prognosis: Excellent with initiative of treatment shortly after birth
 
Disease: Hyperammonemia (Hyperornithinemia, Homocitrullinuria Syndrome)
Metabolite: Orn
Incidence: Unknown (Only 50 Cases Reported Internationally)
Symptoms: Developmental delay, seizures, retarded growth, learning disability , and even neonatal death
Treatment: Ornithine and arginine supplementation in patient’s daily diet proved to lower ammonia levels in the body
Age of Onset: At Birth
Metabolite Concentration
Level Range:
Patient has condition if Orn < 345
Prognosis: 100% mortality if untreated, there is a direct correlation between the duration of hyper-ammonemic coma and morbidity (mental retardation, developmental delays, cortical atrophy), and good prognosis if disorder is treated prospectively from birth
 
Disease: Ketotic Hyperglycinemia
Metabolite: Gly
Incidence: Unknown
Symptoms: Ketoacidosis, low blood sugar, intense hunger, headaches, loss or weakening of the body’s basic motor functions, convulsions and loss of focus, as well as ketosis (a state in metabolism wherein the liver converts fat into fatty acids and ketone bodies that are normally used by the body as an alternative energy source. Also the level of ketone itself may slowly decarboxylate into acetone, which may be toxic to the body.
Treatment: Extended fasts should be avoided. The child should be given a bedtime snack of carbohydrates and should be awakened and fed after the usual duration of sleep. If the child is underweight, a daily nutritional supplement may be recommended. If a spell begins, carbohydrates and fluids should be given promptly. If vomiting prevents this, the child should be taken to the local emergency department for a few hours of intravenous saline and dextrose.
Age of Onset: Within hours of birth
Metabolite Concentration
Level Range:
60 mg per deciliter or less is highly suspicious of hypoglycemia
Prognosis: 100% mortality if untreated but if treatment initiation is shortly after birth, patient exhibits minimum symptoms with probable chance of developing normal
 
Disease: Nonketotic Hyperglycinemia (NKH)
Metabolite: Gly
Incidence: 1 in 55,000
Symptoms: Neurological symptoms are muscular hypotonia, seizures, respiratory distress, and lethargy due to elevated levels of glycine in the cerebrospinal fluid (CSF)
Treatment: Treatment is difficult because the removal of glycine levels in the cerebrospinal fluid by itself is not to avoid symptoms. However, doses of diazepam and dextromethorphan have proved to be beneficial through minimizing the intensity and frequency of the symptoms
Age of Onset: Within hours of birth
Metabolite Concentration
Level Range:
Patient has condition if Gly < 1200 μmol/L….. The definition of hypoglycemia depends on the age of the child. <55 mg/dl in children <35-45 mg/dl in neonates. The diagnosis of nonketotic hyperglycinemia is considered to depend upon the presence of increased cerebrospinal fluid glycine and an increased cerebrospinal fluid to plasma glycine ratio.
Prognosis: Unknown
 
Disease: Hyperornithinemia with Gyral Atrophy (HOGA)
Metabolite: Orn
Incidence: Unknown
Symptoms: Decreased night vision, complete blindness around 50 years of age, mild muscle weakness, but patients is usually overall develop normally
Treatment: A few gyrate atrophy patients will respond to pharmacologic doses of vitamin B6 (pyridoxine) with increase in residual enzyme activity, partial reduction in plasma Ornithine and stabilization of vision. The slow progression of the degenerative changes in vision and the difficulty in measuring small changes in ocular function make evaluation of any therapy difficult. Additional approaches to therapy may be efficacious, including dietary reduction in Ornithine and administration of creatine
Age of Onset: Within days of birth
Metabolite Concentration
Level Range:
Patient has condition if Orn < 345 μmol/L
Prognosis: Unknown
 
Disease: Maple Syrup Urine Disease (MSUD)
Metabolite: Leu, Leu/Ala, Val
Incidence: 1 in 185,000
Symptoms: Loss of appetite, vomiting, poor weight gain, increasing lethargy (difficult to wake up), characteristic burned sugar smell to urine, changes in muscle tone, muscle spasms, and seizures
Treatment: The main treatment for maple syrup urine disease is restriction of dietary forms of the three amino acids leucine, isoleucine, and valine. These restrictions must be lifelong. There are several commercial formulas and foods for individuals with MSUD.
Age of Onset: Infants 4-7 days old
Metabolite Concentration
Level Range:
Patient has condition if Val < 273 μmol/L, Leu < 320 μmol/L
Prognosis: This disease can be life threatening if untreated. Even with dietary treatment, stressful situations and illness can still cause high levels of certain amino acids. Death may occur during these episodes. With strict dietary treatment, children have grown into healthy adulthood.
 
Disease: Ornithine Transcarbamylase Deficiency (OTC)
Metabolite: Orn
Incidence: 1 in 80,000
Symptoms: Anorexia, Irritability, Heavy or rapid breathing, Lethargy, Vomiting, Disorientation, Somnolence, Asterixis (rare), Combativeness, Obtundation, Coma, Cerebral edema or even Death (if treatment is not forthcoming or effective)
Treatment: High Carbohydrate and Protein restricted diet, arginine supplements, and Sodium phenylacetate and sodium benzoate
Age of Onset: Earliest as disorder present at birth
Prognosis: Timely diagnosis and treatment usually results in a good prognosis with normal growth and learning abilities - treatment is lifelong. In some severe cases, high ammonia levels can cause complications even with treatment.
 
Disease: 5-Oxoprolinuria (Pyroglutamic Aciduria)
Metabolite: 5-Oxopro
Incidence: Unknown
Symptoms: Metabolic acidosis, hemolytic anemia, jaundice and urinary excretion of large amounts of 5-oxoproline in body. Neurological symptoms such as ataxia, spasticity and/or seizures may result from chronic metabolic acidosis, if not treated.
Treatment: Early diagnosis and prompt treatment is essential for an improved prognosis. Individuals with GSD require prompt correction of any metabolic acidosis and/or hyperbilirubinemia to help prevent brain damage. Oral maintenance doses of sodium bicarbonate or citrate may help to correct chronic acidosis. Anemia may require transfusions and any electrolyte imbalances should be corrected. Patients with generalized GSD may have heightened sensitivity to oxidative stress, and large doses of vitamin E and vitamin C may be indicated Aggressive medical management is necessary during any intercurrent illness.
Age of Onset: At Birth
Prognosis: Unknown
 
Disease: Phenylketonuria (PKU)
Metabolite: Phe, Phe/Tyr
Incidence: 1 per 13,500 to 1 per 19,000
Symptoms: Left untreated, this condition can cause problems with brain development, leading to progressive mental retardation, brain damage, and seizures.
Treatment: However, PKU is one of the few genetic diseases that can be controlled by diet. A diet low in phenylalanine and high in tyrosine can be a very effective treatment. There is no cure. Damage done is irreversible so early detection is crucial.
Age of Onset: Less than 1 year old
Metabolite Concentration
Level Range:
Patient has condition if Phe < 132 μmol/L
Prognosis: Excellent with initiation of treatment shortly after birth
 
Disease: Tyrosinemia (Type II and Type III)
Metabolite: Tyr/Met
Incidence: 1 in 100,000
Symptoms:

Acute Form - poor appetite and failure to grow normally, vomiting, diarrhea, bloody stools, a cabbage-like odor, jaundice (yellow skin and whites of eyes), swollen liver, irritability, and lethargy (overwhelming tiredness).
Chronic Form - Cirrhosis of the liver; pain, numbness, and tingling in parts of the body (polyneuropathy), kidney problems, and episodes of intense abdominal pain.

Treatment: Restrict the amount of tyrosine and phenylalanine in the baby's food. Nitisinone reduces the toxic effects of tyrosine in the body. The medication, when used along with the dietary restrictions, has been successful in reducing the symptoms of tyrosinemia type I. The last method of treatment is a liver transplant. Now, thanks to nitisinone, surgery is reserved for severe cases of liver damage or cancer. However transplantation carries many risks with it, including the rejection of the new liver by the body.
Age of Onset: Less than 1 year of age
Metabolite Concentration
Level Range:
Patient has condition if Tyr >336 μM tyrosine (or >9.1 mg/dL)
Prognosis: When treatment is started early, severe liver, kidney, and neurologic symptoms can be prevented. Children who are treated usually have normal growth and intelligence. If treatment is not started right away, children may have some liver or kidney damage. Rickets may already be present and need to be treated. Delays in growth and development may also be present. The effects of delayed treatment vary from child to child.