That MMA can have disastrous effects on the nervous system has been long reported; however, the mechanism by which this occurs has never been determined. Published on June 15th 2015, research performed on the effects of methylmalonic acid on neurons isolated from fetal rats in an in vitro setting using a control group of neurons treated with an alternate acid of similar pH. These tests have suggested that methylmalonic acid causes decreases in cellular size and increase in the rate of cellular apoptosis in a concentration dependent manner with more extreme effects being seen at higher concentrations. Furthermore, micro-array analysis of these treated neurons have also suggested that on a epigenetic-level methylmalonic acid alters the transcription rate of 564 genes, notably including those involved in the apoptosis, p53, and MAPK signaling pathways.

No sexual predilection is observed because the deficiency of glycogen synthetase activity is inherited as an autosomal recessive trait.

The overall frequency of glycogen-storage disease is approximately 1 case per 20,000–25,000 people. Glycogen-storage disease type 0 is a rare form, representing less than 1% of all cases. The identification of asymptomatic and oligosymptomatic siblings in several glycogen-storage disease type 0 families has suggested that glycogen-storage disease type 0 is underdiagnosed.

The addition of SPCD to newborn screening panels has offered insight into the incidence of the disorder around the world. In Taiwan, the incidence of SPCD in newborns was estimated to be approximately 1:67,000, while maternal cases were identified at a higher frequency of approximately 1:33,000. The increased incidence of SPCD in mothers compared to newborns is not completely understood. Estimates of SPCD in Japan have shown a similar incidence of 1:40,000. Worldwide, SPCD has the highest incidence in the relatively genetically isolated Faroe Islands, where an extensive screening program was instituted after the sudden death of two teenagers. The incidence in the Faroe Islands is approximately 1:200.

The prognosis will vary depending on the severity of the condition and the individual's response to treatment. Prognosis is typically better for those with cobalamin-responsive variants and not promising in those suffering from noncobalamin-responsive variants, typically the milder variants have a higher frequency of appearance in the population than the more severe ones. Even with dietary modification and continued medical care, it may not be possible to prevent neurological damage in those with a nonresponsive acidemia. Without proper treatment or diagnosis, it not uncommon for the first acidemic attack to be fatal.

Despite these challenges, since it was first identified in 1967, treatment and understanding of the condition has improved to the point where it is not unheard of for even those with unresponsive forms of methylmalonic acidemia to be able to reach adulthood and even carry and deliver children safely.

Infant mortality is high for patients diagnosed with early onset; mortality can occur within less than 2 months, while children diagnosed with late-onset syndrome seem to have higher rates of survival. Patients suffering from a complete lesion of mut0 have not only the poorest outcome of those suffering from methylaonyl-CoA mutase deficiency, but also of all individuals suffering from any form of methylmalonic acidemia.

Overall, according to a study in British Columbia, approximately 2.3 children per 100,000 births (1 in 43,000) have some form of glycogen storage disease. In the United States, they are estimated to occur in 1 per 20,000–25,000 births. Dutch incidence rate is estimated to be 1 per 40,000 births.

Carnitine deficiency has been extensively studied, although most commonly as a secondary finding to other metabolic conditions. The first case of SPCD was reported in the 1980s, in a child with fasting hypoketotic hypoglycemia that resolved after treatment with carnitine supplementation. Later cases were reported with cardiomyopathy and muscle weakness. Newborn screening expanded the potential phenotypes associated with SPCD, to include otherwise asymptomatic adults.

A Glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by enzyme deficiencies affecting either glycogen synthesis, glycogen breakdown or glycolysis (glucose breakdown), typically within muscles and/or liver cells.

GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism (genetically defective enzymes) involved in these processes. In livestock, acquired GSD is caused by intoxication with the alkaloid castanospermine.

Orotic aciduria is a disease yielding an excessive excretion of orotic acid in urine. It causes a characteristic form of anemia and may be associated with mental and physical retardation.

Orotic acid is an intermediate product in pyrimidine synthesis pathway, a subsequent product of which plays a role in conversion between dihydrofolate and tetrahydrofolate. Orotic aciduria is associated with megaloblastic anemia due to decreased pyrimidine synthesis, which leads to decreased nucleotide-lipid cofactors needed for erythrocyte membrane synthesis in the bone marrow.

In addition to the characteristic excessive orotic acid in the urine, patients typically have megaloblastic anemia (UMP synthase deficiency) which cannot be cured by administration of vitamin B12 or folic acid.

It also can cause inhibition of RNA and DNA synthesis and failure to thrive.

At present, no specific enzyme deficiency nor genetic mutation has been implicated as the cause of hypertryptophanemia. Several known factors regarding tryptophan metabolism and kynurenines, however, may explain the presence of behavioral abnormalities seen with the disorder.

Tryptophan is an essential amino acid, and is required for protein synthesis. Aside from this crucial role, the remainder of tryptophan is primarily metabolized along the kynurenine pathway in most tissues, including those of the brain and central nervous system.

As the main defect behind hypertryptophanemia is suspected to alter and disrupt the metabolic pathway from tryptophan to kynurenine, a possible correlation between hypertryptophanemia and the known effects of kynurenines on neuronal function, physiology and behavior may be of interest.

One of these kynurenines, aptly named kynurenic acid, serves as a neuroprotectant through its function as an antagonist at both nicotinic and glutamate receptors (responsive to the neurotransmitters nicotine and glutamate, respectively). This action is in opposition to the agonist quinolinic acid, another kynurenine, noted for its potential as a neurotoxin. Quinolinic acid activity has been associated with neurodegenerative disorders such as Huntington's disease, the neuroprective abilities of kynurenic acid forming a counterbalance against this process, and the related excitotoxicity and similar damaging effects on neurons.

Indoleic acid excretion is another indicator of hypertryptophanemia. Indirectly related to kynurenine metabolism, indole modifies neural function and human behavior by interacting with voltage-dependent sodium channels (integral membrane proteins that form ion channels, allowing vital synaptic action potentials).

Methylmalonyl-CoA mutase is a mitochondrial homodimer apoenzyme (EC. 5. 4.99.2) that focuses on the catalysis of methylmalonyl CoA to succinyl CoA. The enzyme is bound to adenosylcobalamin, a hormonal derivative of vitamin B12 in order to function. Methylmalonyl-CoA mutase deficiency is caused by genetic defect in the MUT gene responsible for encoding the enzyme. Deficiency in this enzyme accounts for 60% of the cases of methylmalonic acidemia.

Hypertryptophanemia, also called familial hypertryptophanemia, is a rare autosomal recessive metabolic disorder that results in a massive buildup of the amino acid tryptophan in the blood, with associated symptoms and tryptophanuria ("-uria" denotes "in the urine").

Elevated levels of tryptophan are also seen in Hartnup disease, a disorder of amino acid transport. However, the increase of tryptophan in that disorder is negligible when compared to that of hypertryptophanemia.

Arakawa's syndrome II is an autosomal dominant metabolic disorder that causes a deficiency of the enzyme tetrahydrofolate-methyltransferase; affected individuals cannot properly metabolize methylcobalamin, a type of Vitamin B.

It is also called Methionine synthase deficiency, Tetrahydrofolate-methyltransferase deficiency syndrome, and N5-methylhomocysteine transferase deficiency.

Since the essential pathology is due to the inability to absorb vitamin B from the bowels, the solution is therefore injection of IV vitamin B. Timing is essential, as some of the side effects of vitamin B deficiency are reversible (such as RBC indices, peripheral RBC smear findings such as hypersegmented neutrophils, or even high levels of methylmalonyl CoA), but some side effects are irreversible as they are of a neurological source (such as tabes dorsalis, and peripheral neuropathy). High suspicion should be exercised when a neonate, or a pediatric patient presents with anemia, proteinuria, sufficient vitamin B dietary intake, and no signs of pernicious anemia.

Arakawa's syndrome II is inherited in an autosomal dominant manner. This means the defective gene responsible for disorder is located on an autosome, and one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who has the disorder.

Abetalipoproteinemia affects the absorption of dietary fats, cholesterol, and certain vitamins. People affected by this disorder are not able to make certain lipoproteins, which are molecules that consist of proteins combined with cholesterol and particular fats called triglycerides. This leads to a multiple vitamin deficiency, affecting the fat-soluble vitamin A, vitamin D, vitamin E, and vitamin K. However, many of the observed effects are due to vitamin E deficiency in particular.

The signs and symptoms of abetalipoproteinemia appear in the first few months of life (because pancreatic lipase is not active in this period). They can include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; abnormal spiny red blood cells (acanthocytosis); and fatty, foul-smelling stools (steatorrhea). The stool may contain large chunks of fat and/or blood. Other features of this disorder may develop later in childhood and often impair the function of the nervous system. They can include poor muscle coordination, difficulty with balance and movement (ataxia), and progressive degeneration of the retina (the light-sensitive layer in the posterior eye) that can progress to near-blindness (due to deficiency of vitamin A, retinol). Adults in their thirties or forties may have increasing difficulty with balance and walking. Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which typically results in eye problems with degeneration of the spinocerebellar and dorsal column tracts.

A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems (especially the nervous system, muscles, and intestines) in affected infants. The most common subtype is CDG-Ia (also referred to as PMM2-CDG) where the genetic defect leads to the loss of phosphomannomutase 2, the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate.

Abetalipoproteinemia is a disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.

It is a rare autosomal recessive disorder.

This is a rare disease with prevalence about 1 in 200,000 to 1 in 600,000. Studies showed that mutations in "CUBN" or "AMN" clustered particularly in the Scandinavian countries and the Eastern Mediterranean regions. Founder effect, higher clinical awareness to IGS, and

frequent consanguineous marriages all play a role in the higher prevalence of IGS among these populations

No treatment is available for most of these disorders. Mannose supplementation relieves the symptoms in PMI-CDG (CDG-Ib) for the most part, even though the hepatic fibrosis may persist. Fucose supplementation has had a partial effect on some SLC35C1-CDG (CDG-IIc or LAD-II) patients.

Analbuminaemia or analbuminemia is a genetically inherited metabolic defect characterised by an impaired synthesis of serum albumin. Although albumin is the most common serum protein, analbuminaemia is a benign condition.

Morquio syndrome (referred to as mucopolysaccharidosis IV, MPS IV, Morquio-Brailsford syndrome, or Morquio) is a rare metabolic disorder in which the body cannot process certain types of mucopolysaccharides. This birth defect, which is autosomal recessive, is thus a lysosomal storage disorder that is usually inherited. In the US, the incidence rate for Morquio is estimated at between 1 in 200,000 and 1 in 300,000 live births.

The build-up or elimination of mucopolysaccharides, rather than processing by their usual biochemical pathways, causes various symptoms. These involve accumulation of keratan sulfate.

A deficiency of vitamin B alone is relatively uncommon and often occurs in association with other vitamins of the B complex. The elderly and alcoholics have an increased risk of vitamin B deficiency, as well as other micronutrient deficiencies. Evidence exists for decreased levels of vitamin B in women with type 1 diabetes and in patients with systemic inflammation, liver disease, rheumatoid arthritis, and those infected with HIV. Use of oral contraceptives and treatment with certain anticonvulsants, isoniazid, cycloserine, penicillamine, and hydrocortisone negatively impact vitamin B status. Hemodialysis reduces vitamin B plasma levels.