Diagnosis of Molybdenum cofactor deficiency includes early seizures, low blood levels of uric acid, and high levels of sulphite, xanthine, and uric acid in urine. Additionally, the disease produces characteristic MRI images that can aid in diagnosis.

Another common symptom of copper deficiency is peripheral neuropathy, which is numbness or tingling that can start in the extremities and can sometimes progress radially inward towards the torso. In an Advances in Clinical Neuroscience & Rehabilitation (ACNR) published case report, a 69-year-old patient had progressively worsened neurological symptoms. These symptoms included diminished upper limb reflexes with abnormal lower limb reflexes, sensation to light touch and pin prick was diminished above the waist, vibration sensation was lost in the sternum, and markedly reduced proprioception or sensation about the self’s orientation. Many people suffering from the neurological effects of copper deficiency complain about very similar or identical symptoms as the patient. This numbness and tingling poses danger for the elderly because it increases their risk of falling and injuring themselves. Peripheral neuropathy can become very disabling leaving some patients dependent on wheel chairs or walking canes for mobility if there is lack of correct diagnosis. Rarely can copper deficiency cause major disabling symptoms. The deficiency will have to be present for an extensive amount of time until such disabling conditions manifest.

When caused by a mutation in the MOCS1 gene it is the type A variant. It can also be caused by a mutation in the MOCS2 gene or the GEPH gene. As of 2010, there had been approximately 132 reported cases.

It should not be confused with molybdenum deficiency.

Some patients suffering from copper deficiency have shown signs of vision and color loss. The vision is usually lost in the peripheral views of the eye. The bilateral vision loss is usually very gradual. An optical coherence tomography (OCT) shows some nerve fiber layer loss in most patients, suggesting the vision loss and color vision loss was secondary to optic neuropathy or neurodegeneration.

Short-chain acyl-coenzyme A dehydrogenase deficiency affected infants will have vomiting, low blood sugar, a lack of energy (lethargy), poor feeding, and failure to gain weight and grow. Additional features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delays, and microcephaly. The symptoms of short-chain acyl-CoA dehydrogenase deficiency may be triggered during illnesses such as viral infections. In some cases, signs and symptoms may not appear until adulthood, when some individuals may develop muscle weakness, while other individuals mild symptoms may never be diagnosed.

Babies with this disorder are usually healthy at birth. The signs and symptoms may not appear until later in infancy or childhood and can include poor feeding and growth (failure to thrive), a weakened and enlarged heart (dilated cardiomyopathy), seizures, and low numbers of red blood cells (anemia). Another feature of this disorder may be very low blood levels of carnitine (a natural substance that helps convert certain foods into energy).

Isobutyryl-CoA dehydrogenase deficiency may be worsened by long periods without food (fasting) or infections that increase the body's demand for energy. Some individuals with gene mutations that can cause isobutyryl-CoA dehydrogenase deficiency may never experience any signs and symptoms of the disorder.

Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, lethargy, hypoglycemia, hypotonia, liver problems, and abnormally high levels of hyperinsulinism. Insulin controls the amount of sugar that moves from the blood into cells for conversion to energy. Individuals with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden unexpected death.

Problems related to 3-hydroxyacyl-coenzyme A dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

SBCADD is included as a secondary target condition in most newborn screening programs, as the key analyte is the same as is used to identify isovaleric acidemia. Most cases have been Hmong individuals, who are asymptomatic. There are isolated case reports where individuals have been identified with SBCADD in addition to developmental delay and epilepsy. It is currently unclear what the complete clinical presentation of SBCADD looks like. There is some concern that these cases with additional symptoms may reflect an ascertainment bias rather than being a true representation of the clinical spectrum of the disease. Currently, there is no accepted treatment, as most affected individuals do not require any. Some recommend avoidance of valproic acid, as it can be a substrate for 2-methylbutyryl-CoA dehydrogenase.

D-Bifunctional protein deficiency (officially called 17β-hydroxysteroid dehydrogenase IV deficiency) is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs, such as alcohol. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome.

Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment. Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life.

Short-chain acyl-coenzyme A dehydrogenase deficiency (SCADD), also called ACADS deficiency and SCAD deficiency, is an autosomal recessive fatty acid oxidation disorder which affects enzymes required to break down a certain group of fats called short chain fatty acids.

Isobutyryl-coenzyme A dehydrogenase deficiency, commonly known as IBD deficiency, is a rare metabolic disorder in which the body is unable to process certain amino acids properly.

People with this disorder have inadequate levels of an enzyme that helps break down the amino acid valine, resulting in a buildup of valine in the urine, a symptom called valinuria.

Saccharopinuria (an excess of saccharopine in the urine), also called saccharopinemia, saccharopine dehydrogenase deficiency or alpha-aminoadipic semialdehyde synthase deficiency, is a variant form of hyperlysinemia. It is caused by a partial deficiency of the enzyme saccharopine dehydrogenase, which plays a secondary role in the lysine metabolic pathway. Inheritance is thought to be autosomal recessive, but this cannot be established as individuals affected by saccharopinuria typically have only a 40% reduction in functional enzyme.

PDCD is generally presented in one of two forms. The metabolic form appears as lactic acidosis. The neurological form of PDCD contributes to hypotonia, poor feeding, lethargy and structural abnormalities in the brain. Patients may develop seizures and/or neuropathological spasms. These presentations of the disease usually progress to mental retardation, microcephaly, blindness and spasticity.

Females with residual pyruvate dehydrogenase activity will have no uncontrollable systemic lactic acidosis and few, if any, neurological symptoms. Conversely, females with little to no enzyme activity will have major structural brain abnormalities and atrophy. Males with mutations that abolish, or almost abolish, enzyme activity presumably die in utero because brain cells are not able to generate enough ATP to be functionally viable. It is expected that most cases will be of mild severity and have a clinical presentation involving lactic acidosis.

Prenatal onset may present with non-specific signs such as low Apgar scores and small for gestational age. Metabolic disturbances may also be considered with poor feeding and lethargy out of proportion to a mild viral illness, and especially after bacterial infection has been ruled out. PDH activity may be enhanced by exercise, phenylbutyrate and dichloroacetate.

The clinical presentation of congenital PDH deficiency is typically characterized by heterogenous neurological features that usually appear within the first year of life. In addition, patients usually show severe hyperventillation due to profound metabolic acidosis mostly related to lactic acidosis. Metabolic acidosis in these patients is usually refractory to correction with bicarbonate.

Typically, initial signs and symptoms of this disorder occur during infancy and include low blood sugar (hypoglycemia), lack of energy (lethargy), and muscle weakness. There is also a high risk of complications such as liver abnormalities and life-threatening heart problems. Symptoms that begin later in childhood, adolescence, or adulthood tend to be milder and usually do not involve heart problems. Episodes of very long-chain acyl-coenzyme A dehydrogenase deficiency can be triggered by periods of fasting, illness, and exercise.

It is common for babies and children with the early and childhood types of VLCADD to have episodes of illness called metabolic crises. Some of the first symptoms of a metabolic crisis are: extreme sleepiness, behavior changes, irritable mood, poor appetite.

Some of these other symptoms of VLCADD in infants may also follow: fever, nausea, diarrhea, vomiting, hypoglycemia.

3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADH deficiency) is a rare condition that prevents the body from converting certain fats to energy, particularly during fasting. Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to metabolize fats and convert them to energy. People with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency have inadequate levels of an enzyme required for a step that metabolizes groups of fats called medium chain fatty acids and short chain fatty acids; for this reason this disorder is sometimes called medium- and short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (M/SCHAD) deficiency.

2-Methylbutyryl-CoA dehydrogenase deficiency, also called 2-Methylbutyryl glycinuria or short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD), is an autosomal recessive metabolic disorder. It causes the body to be unable to process the amino acid isoleucine properly. Initial case reports identified individuals with developmental delay and epilepsy, however most cases identified through newborn screening have been asymptomatic.

In addition to the symptoms associated with immunodeficiency, such as depletion of T-cells, decline of lymphocyte activity, and an abrupt proliferation of both benign and opportunistic infections — PNP-deficiency is often characterized by the development of autoimmune disorders. lupus erythematosus, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura have been reported with PNP-deficiency.

Neurological symptoms, such as developmental decline, hypotonia, and mental retardation have also been reported.

6-Pyruvoyltetrahydropterin synthase deficiency is an autosomal recessive disorder that causes malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency.

It belongs to the rare diseases. It is a recessive disorder that is accompanied by hyperphenylalaninemia. Commonly reported symptoms are initial truncal hypotonia, subsequent appendicular hypertonia, bradykinesia, cogwheel rigidity, generalized dystonia, and marked diurnal fluctuation. Other reported clinical features include difficulty in swallowing, oculogyric crises, somnolence, irritability, hyperthermia, and seizures. Chorea, athetosis, hypersalivation, rash with eczema, and sudden death have also been reported. Patients with mild phenotypes may deteriorate if given folate antagonists such as methotrexate, which can interfere with a salvage pathway through which dihydrobiopterin is converted into tetrahydrobiopterin via dihydrofolate reductase. Treatment options include substitution with neurotransmitter precursors (levodopa, 5-hydroxytryptophan), monoamine oxidase inhibitors, and tetrahydrobiopterin. Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

If a metabolic crisis is not treated, a child with VLCADD can develop: breathing problems, seizures, coma, sometimes leading to death.

The term fatty acid oxidation disorder (FAOD) is sometimes used, especially when there is an emphasis on the oxidation of the fatty acid.

In addition to the fetal complications, they can also cause complications for the mother during pregnancy.

Examples include:

- trifunctional protein deficiency

- MCADD, LCHADD, and VLCADD

Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This rare form of the disorder may appear benign at times, but often involves seizures, convulsions, and intellectual disability.

Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of lactic acid in the blood, such as lactic acidemia, are likely to have elevated proline levels, because lactic acid inhibits the breakdown of proline.

The signs/symptoms of this condition are consistent with the following:

- Intellectual disability,

- Muscular hypotonia

- Encephalitis

- Seizures

- Aphasia

Signs and symptoms of this disorder include weak muscle tone (hypotonia), sagging facial features, seizures, intellectual disability, and developmental delay. The patients have brittle hair and metaphyseal widening. In rare cases, symptoms begin later in childhood and are less severe. Affected infants may be born prematurely. Symptoms appear during infancy and are largely a result of abnormal intestinal copper absorption with a secondary deficiency in copper-dependent mitochondrial enzymes. Normal or slightly slowed development may proceed for 2 to 3 months, and then there will be severe developmental delay and a loss of early developmental skills. Menkes Disease is also characterized by seizures, failure to thrive, subnormal body temperature, and strikingly peculiar hair, which is kinky, colorless or steel-colored, and easily broken. There can be extensive neurodegeneration in the gray matter of the brain. Arteries in the brain can also be twisted with frayed and split inner walls. This can lead to rupture or blockage of the arteries. Weakened bones (osteoporosis) may result in fractures.

Occipital horn syndrome (sometimes called X-linked cutis laxa or Ehlers-Danlos type 9) is a mild form of Menkes syndrome that begins in early to middle childhood. It is characterized by calcium deposits in a bone at the base of the skull (occipital bone), coarse hair, loose skin, and joints.

It is difficult to determine the prevalence of hyperprolinemia type I, as many people with the condition are asymptomatic.

People with hyperprolinemia type I have proline levels in their blood between 3 and 10 times the normal level. Some individuals with type I exhibit seizures, intellectual disability, or other neurological problems.

Purine nucleoside phosphorylase deficiency, often called PNP-deficiency, is a rare autosomal recessive metabolic disorder which results in immunodeficiency.