Metabolic diseases - a broad category of disorders

Metabolic diseases are a broad category of disorders that affect the body's ability to properly process and convert nutrients into energy. These diseases can result from enzyme deficiencies, hormone imbalances, or problems with the biochemical pathways involved in metabolism. Below is a list of some of the most common and well-known metabolic diseases, but this is not exhaustive as there are hundreds of known metabolic disorders, including very rare genetic conditions.

Inherited Metabolic Disorders (Inborn Errors of Metabolism)

Phenylketonuria (PKU) - Caused by a deficiency of the enzyme phenylalanine hydroxylase, leading to the accumulation of phenylalanine in the body, which can cause brain damage if untreated.
Maple Syrup Urine Disease (MSUD) - Caused by the body's inability to break down certain amino acids (leucine, isoleucine, and valine), leading to toxic buildup and severe neurological issues.
Gaucher Disease - A lysosomal storage disorder where the body lacks the enzyme glucocerebrosidase, leading to the accumulation of glucocerebroside in various organs.
Tay-Sachs Disease - A rare genetic disorder caused by the absence of the enzyme hexosaminidase A, leading to the buildup of gangliosides in nerve cells.
Fabry Disease - A lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A, leading to the accumulation of globotriaosylceramide in various tissues.
Pompe Disease (Glycogen Storage Disease Type II) - Caused by a deficiency of the enzyme acid alpha-glucosidase, leading to the buildup of glycogen in the muscles and other tissues.
Galactosemia - Caused by a deficiency in the enzyme galactose-1-phosphate uridylyltransferase, leading to the inability to process galactose properly.
Ornithine Transcarbamylase Deficiency (OTC Deficiency) - A urea cycle disorder that leads to the accumulation of ammonia in the body due to the inability to convert ammonia into urea for excretion.
Methylmalonic Acidemia (MMA) - Caused by the body's inability to process certain fats and proteins properly, leading to a toxic buildup of methylmalonic acid.
Homocystinuria - A disorder of methionine metabolism leading to an abnormal accumulation of homocysteine in the blood and urine.
Lesch-Nyhan Syndrome - Caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT), resulting in an overproduction of uric acid.
Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) - A fatty acid oxidation disorder where the body cannot break down medium-chain fatty acids, leading to episodes of hypoglycemia.
Wilson's Disease - A disorder in which copper builds up in the liver, brain, and other organs due to defective copper transport and excretion.
Zellweger Syndrome - A peroxisomal disorder caused by the impaired function of peroxisomes, which leads to the buildup of toxic substances and affects many organs, especially the brain and liver.
Hereditary Fructose Intolerance - Caused by a deficiency of aldolase B, leading to the accumulation of fructose-1-phosphate in the liver.
Cystinosis - A rare genetic condition that causes the amino acid cystine to accumulate in various tissues, especially the kidneys and eyes.
Carnitine Palmitoyltransferase II Deficiency (CPT II Deficiency) - A disorder of fatty acid oxidation, leading to muscle weakness, rhabdomyolysis, and metabolic crises.
Biotinidase Deficiency - A disorder in which the body is unable to recycle the vitamin biotin, leading to neurological and skin symptoms if untreated.

Diabetes and Related Metabolic Diseases

Type 1 Diabetes - An autoimmune disease where the pancreas does not produce insulin, leading to high blood sugar levels.
Type 2 Diabetes - A metabolic disorder where the body becomes resistant to insulin, leading to high blood sugar levels.
Maturity-Onset Diabetes of the Young (MODY) - A form of diabetes caused by a genetic mutation that affects insulin production.
Gestational Diabetes - A type of diabetes that develops during pregnancy and can affect both the mother and baby's health.

Thyroid-Related Metabolic Diseases

Hypothyroidism - A condition where the thyroid gland does not produce enough thyroid hormones, slowing metabolism.
Hyperthyroidism - A condition where the thyroid gland produces too much thyroid hormone, accelerating metabolism.
Hashimoto's Thyroiditis - An autoimmune disease where the immune system attacks the thyroid gland, often leading to hypothyroidism.
Graves' Disease - An autoimmune disorder that causes hyperthyroidism by overstimulating the thyroid.

Lipid and Cholesterol Metabolism Disorders

Familial Hypercholesterolemia - A genetic disorder where the body is unable to remove low-density lipoprotein (LDL) cholesterol, leading to high cholesterol levels and an increased risk of heart disease.
Hyperlipidemia - A condition where there is an abnormally high level of lipids (fats) in the blood.
Tangier Disease - A rare disorder characterized by the absence of high-density lipoprotein (HDL), leading to an increased risk of cardiovascular disease.
Refsum Disease - A disorder of phytanic acid metabolism, leading to the accumulation of this substance and affecting the nervous system.
Smith-Lemli-Opitz Syndrome - A disorder of cholesterol metabolism that affects multiple systems, including brain development and growth.

Glycogen Storage Diseases (GSD)

Glycogen Storage Disease Type I (Von Gierke's Disease) - Caused by a deficiency in glucose-6-phosphatase, leading to severe hypoglycemia.
Glycogen Storage Disease Type II (Pompe Disease) - Caused by a deficiency in acid maltase, affecting muscle function.
Glycogen Storage Disease Type III (Cori's Disease) - Caused by a deficiency in the debranching enzyme, leading to the buildup of abnormal glycogen in the liver and muscles.
Glycogen Storage Disease Type V (McArdle Disease) - Caused by a deficiency in muscle phosphorylase, leading to muscle pain and fatigue during exercise.

Mitochondrial Disorders

Mitochondrial Myopathy - A group of disorders caused by mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function and lead to muscle weakness and other symptoms.
Leigh Syndrome - A severe neurological disorder caused by mitochondrial dysfunction, often leading to developmental regression and respiratory failure.
MELAS Syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) - A mitochondrial disorder affecting multiple systems, including muscles and the brain.
Kearns-Sayre Syndrome - A mitochondrial disorder that affects the eyes, muscles, heart, and other tissues.

Peroxisomal Disorders

Adrenoleukodystrophy (ALD) - A peroxisomal disorder that affects the metabolism of very long-chain fatty acids, leading to neurological deterioration.
Rhizomelic Chondrodysplasia Punctata (RCDP) - A disorder affecting the formation and function of peroxisomes, leading to skeletal abnormalities and developmental delays.

Lysosomal Storage Diseases

Hurler Syndrome (MPS I) - A mucopolysaccharidosis disorder caused by the deficiency of the enzyme alpha-L-iduronidase, leading to the accumulation of glycosaminoglycans.
Hunter Syndrome (MPS II) - Another mucopolysaccharidosis disorder caused by a deficiency in iduronate sulfatase, affecting multiple organs and systems.
Niemann-Pick Disease - A group of inherited metabolic disorders where harmful amounts of lipids accumulate in the brain, liver, and spleen.
Krabbe Disease - A lysosomal storage disease caused by the deficiency of the enzyme galactocerebrosidase, leading to severe neurological damage.

Other Metabolic Disorders

Porphyria - A group of disorders caused by abnormalities in the heme production pathway, leading to episodes of abdominal pain, neurological symptoms, and photosensitivity.
Hyperammonemia - A condition characterized by an excess of ammonia in the blood, often due to defects in the urea cycle.
Citrullinemia - A disorder that affects the urea cycle and leads to the accumulation of ammonia and citrulline in the blood.
Alpha-1 Antitrypsin Deficiency - A disorder affecting the liver and lungs due to the buildup of abnormal alpha-1 antitrypsin protein.
Congenital Adrenal Hyperplasia (CAH) - A group of disorders affecting steroid hormone synthesis in the adrenal glands, leading to hormone imbalances.

Other Notable Conditions

Prader-Willi Syndrome - A genetic disorder that affects many parts of the body, including metabolism, leading to obesity and diabetes.
Bardet-Biedl Syndrome - A rare genetic disorder affecting multiple systems, including metabolism, vision, and kidney function.
Metabolic Syndrome - A cluster of conditions (including insulin resistance, obesity, high blood pressure, and dyslipidemia) that increase the risk of cardiovascular disease and type 2 diabetes.

This list covers some of the major metabolic diseases, but there are many other rare and less well-known metabolic conditions, especially in the category of inborn errors of metabolism. These disorders often require specialized care and lifelong management.

Less well-known metabolic conditions, especially in the category of inborn errors of metabolism.

Inborn errors of metabolism (IEMs) are a group of rare genetic disorders caused by defects in specific enzymes that disrupt normal biochemical processes in the body. These defects can result in the accumulation of toxic substances or the inability to produce essential compounds. While some IEMs are relatively well-known, there are hundreds of rare and less-known metabolic conditions that fall into this category.

Here’s a list of some of the rarer and less well-known inborn errors of metabolism:

Amino Acid Metabolism Disorders

Tyrosinemia Type I - Caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (FAH), leading to toxic accumulation of tyrosine byproducts, affecting the liver, kidneys, and nervous system.
Hyperprolinemia Types I & II - Caused by the accumulation of proline due to enzyme deficiencies in proline degradation pathways, potentially leading to neurological symptoms.
Argininosuccinic Aciduria - A urea cycle disorder caused by a deficiency in argininosuccinate lyase (ASL), leading to the accumulation of ammonia in the blood.
Hypermethioninemia - A rare condition characterized by elevated levels of methionine in the blood, often due to deficiencies in methionine adenosyltransferase or other enzymes in methionine metabolism.
Glutaric Aciduria Type I - A defect in the enzyme glutaryl-CoA dehydrogenase, leading to the accumulation of glutaric acid, causing severe neurological damage.
Isovaleric Acidemia - Caused by a deficiency in isovaleryl-CoA dehydrogenase, resulting in the buildup of isovaleric acid, which can lead to metabolic crises and severe illness.
Citrullinemia Type II - A rare form of citrullinemia that is not associated with the urea cycle but results from a mutation in the SLC25A13 gene affecting the transport of citrulline across the mitochondrial membrane.
Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) Syndrome - A urea cycle disorder caused by mutations in the ORNT1 gene, affecting the transport of ornithine into mitochondria, leading to hyperammonemia and neurological issues.

Organic Acidurias

Propionic Acidemia - Caused by a deficiency in the enzyme propionyl-CoA carboxylase, leading to the toxic buildup of propionic acid and resulting in severe metabolic crises.
Methylmalonic Acidemia (MMA) - Another organic acid disorder where the body cannot break down certain proteins and fats, resulting in the buildup of methylmalonic acid. Several subtypes exist depending on the enzyme affected.
Glutaric Acidemia Type II - A disorder of fatty acid oxidation caused by mutations in electron transfer flavoprotein (ETF) or ETF dehydrogenase, leading to severe multi-organ involvement.
3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency (HMG-CoA Lyase Deficiency) - A rare condition affecting ketone body synthesis, resulting in episodes of metabolic acidosis and hypoglycemia.
Isobutyryl-CoA Dehydrogenase Deficiency - A rare disorder in the breakdown of the amino acid valine, leading to muscle weakness, failure to thrive, and developmental delays.
2-Methylbutyryl-CoA Dehydrogenase Deficiency - A disorder of isoleucine metabolism causing organic acidemia, which can present with developmental delays, hypotonia, and neurological symptoms.

Fatty Acid Oxidation Disorders

Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHAD Deficiency) - A disorder of fatty acid oxidation affecting long-chain fatty acids, which can cause hypoglycemia, liver disease, and cardiomyopathy.
Short-Chain Acyl-CoA Dehydrogenase Deficiency (SCADD) - A milder fatty acid oxidation disorder affecting short-chain fatty acids, sometimes associated with developmental delays and metabolic crises.
Trifunctional Protein Deficiency - A disorder of mitochondrial fatty acid oxidation that can affect the heart, liver, and muscles, leading to cardiomyopathy, hypoglycemia, and muscle weakness.
Carnitine Uptake Deficiency (Primary Carnitine Deficiency) - A disorder affecting the transport of carnitine into cells, resulting in muscle weakness, hypoglycemia, and potentially fatal cardiomyopathy.
Carnitine Acylcarnitine Translocase Deficiency (CACT Deficiency) - A severe disorder of fatty acid oxidation affecting the transport of fatty acids into the mitochondria, leading to neonatal metabolic crises.

Carbohydrate Metabolism Disorders

Phosphoglucomutase 1 Deficiency (PGM1 Deficiency) - A disorder of glycogen metabolism that affects the breakdown of glucose, leading to hypoglycemia, muscle weakness, and potentially liver disease.
Tarui Disease (Glycogen Storage Disease Type VII) - A disorder caused by a deficiency of phosphofructokinase, resulting in exercise intolerance, muscle cramps, and myoglobinuria.
Galactokinase Deficiency - A milder form of galactosemia where a deficiency of the enzyme galactokinase leads to cataracts and other complications, but without severe systemic involvement.
Fructose-1,6-Bisphosphatase Deficiency - A rare disorder of gluconeogenesis, leading to episodes of hypoglycemia and metabolic acidosis during fasting or illness.
Pyruvate Carboxylase Deficiency - A disorder affecting the conversion of pyruvate to oxaloacetate, which disrupts gluconeogenesis and the citric acid cycle, leading to developmental delays and lactic acidosis.

Lysosomal Storage Disorders

Sialidosis - A rare lysosomal storage disorder caused by a deficiency of the enzyme neuraminidase, leading to the accumulation of sialic acid-containing compounds, causing neurological and systemic issues.
Mannosidosis - A deficiency in alpha-mannosidase enzyme leading to the accumulation of mannose-rich oligosaccharides, which can cause skeletal abnormalities, hearing loss, and developmental delays.
Wolman Disease - A rare lysosomal storage disorder caused by a deficiency in lysosomal acid lipase, leading to fat accumulation in the liver, spleen, and other tissues.
Multiple Sulfatase Deficiency (MSD) - A condition affecting the breakdown of several sulfated molecules due to a deficiency in multiple sulfatase enzymes, leading to severe neurological and systemic symptoms.
Aspartylglucosaminuria - A lysosomal storage disorder caused by a deficiency of aspartylglucosaminidase, leading to the accumulation of glycoprotein byproducts in various organs and tissues, causing developmental delays and intellectual disability.
Galactosialidosis - A rare disorder resulting from a combined deficiency of beta-galactosidase and neuraminidase, causing symptoms similar to sialidosis, including developmental delay, skeletal abnormalities, and vision loss.

Peroxisomal Disorders

D-Bifunctional Protein Deficiency - A severe peroxisomal disorder affecting the oxidation of very long-chain fatty acids, leading to developmental delays, seizures, and liver dysfunction.
X-Linked Adrenomyeloneuropathy (AMN) - A milder form of X-linked adrenoleukodystrophy (ALD), primarily affecting the spinal cord and peripheral nerves, leading to progressive stiffness and weakness in the legs.
Adult Refsum Disease - A milder form of Refsum disease that affects the metabolism of phytanic acid, leading to vision loss, hearing loss, and peripheral neuropathy.
Acatalasemia - A rare condition caused by a deficiency in the enzyme catalase, which is involved in breaking down hydrogen peroxide in cells. This disorder can cause tissue damage, especially in the mouth and gums.

Congenital Disorders of Glycosylation (CDG)

PMM2-CDG (CDG-Ia) - The most common form of congenital disorders of glycosylation, caused by a deficiency of phosphomannomutase 2, affecting multiple organ systems, including the brain, liver, and muscles.
MPI-CDG (CDG-Ib) - A rare form of CDG affecting the enzyme mannose phosphate isomerase, leading to gastrointestinal issues and liver disease but typically sparing neurological development.
ALG6-CDG - A type of CDG caused by defects in the ALG6 gene, leading to developmental delays, hypotonia, and coagulation disorders.
Cerebrotendinous Xanthomatosis (CTX) - A lipid storage disorder caused by a deficiency in the enzyme sterol 27-hydroxylase, leading to the abnormal accumulation of cholesterol and cholestanol in various tissues.

Other Rare Metabolic Conditions

Menke’s Disease (Kinky Hair Disease) - A disorder of copper metabolism caused by mutations in the ATP7A gene, leading to severe neurological deterioration, connective tissue abnormalities, and distinctive "kinky" hair.
Biotin-Thiamine-Responsive Basal Ganglia Disease - A disorder affecting the metabolism of biotin and thiamine, causing neurological symptoms such as movement disorders and seizures, often responsive to supplementation.
Dihydropyrimidine Dehydrogenase (DPD) Deficiency - A rare disorder affecting the breakdown of pyrimidines (uracil and thymine), leading to neurological issues and sensitivity to certain chemotherapy drugs.
Congenital Sucrase-Isomaltase Deficiency (CSID) - A condition where the body cannot break down certain sugars (sucrose and starch), leading to gastrointestinal symptoms like diarrhea, bloating, and abdominal pain.
Pyruvate Dehydrogenase Complex Deficiency (PDCD) - A disorder affecting the conversion of pyruvate into acetyl-CoA, causing lactic acidosis, developmental delays, and neurological symptoms.
Glutathione Synthetase Deficiency - A disorder in the synthesis of glutathione, an important antioxidant, leading to hemolytic anemia, metabolic acidosis, and neurological symptoms.
Succinyl-CoA:3-Ketoacid CoA Transferase Deficiency (SCOT Deficiency) - A rare disorder affecting ketone body utilization, leading to recurrent episodes of ketoacidosis.

Neurometabolic Disorders

Leigh Syndrome (Subacute Necrotizing Encephalomyelopathy) - A severe neurodegenerative disorder caused by defects in mitochondrial energy production, leading to progressive neurological deterioration.
Alexander Disease - A rare disorder affecting the brain’s white matter, associated with mutations in the GFAP gene, leading to developmental delay, seizures, and progressive neurological symptoms.

This list encompasses many rare inborn errors of metabolism, but there are numerous other ultra-rare disorders within this category. Diagnosis of these conditions often requires specialized biochemical testing, genetic analysis, and metabolic screening, and early detection is critical for managing symptoms and preventing severe complications.

Ultra-rare metabolic disorders

Ultra-rare metabolic disorders are those that affect only a very small number of individuals worldwide, often fewer than 1 in 1,000,000 people. These conditions can be difficult to diagnose and may only be known to a small number of specialists. Below is a list of ultra-rare metabolic disorders, many of which are in the category of inborn errors of metabolism (IEMs).

1. Ribose-5-Phosphate Isomerase Deficiency

Description: This is one of the rarest metabolic disorders ever reported, with only a handful of cases documented. It results from a deficiency in the enzyme ribose-5-phosphate isomerase, a part of the pentose phosphate pathway, which is important for nucleotide synthesis.
Symptoms: Developmental delay, leukoencephalopathy (white matter disease), and seizures.

2. Malonyl-CoA Decarboxylase Deficiency

Description: This disorder is caused by a deficiency in malonyl-CoA decarboxylase, an enzyme involved in fatty acid synthesis and energy production.
Symptoms: Developmental delays, metabolic acidosis, hypotonia, cardiomyopathy, and seizures.

3. Adenylosuccinate Lyase Deficiency

Description: A defect in the purine synthesis pathway due to a deficiency in adenylosuccinate lyase. This disorder disrupts the production of adenosine and guanosine, essential for energy metabolism.
Symptoms: Developmental delays, seizures, autism spectrum-like behaviors, and intellectual disability.

4. L-2-Hydroxyglutaric Aciduria

Description: This is caused by a deficiency in L-2-hydroxyglutarate dehydrogenase, which leads to the accumulation of L-2-hydroxyglutaric acid, a toxic substance.
Symptoms: Progressive neurological symptoms including ataxia, seizures, developmental delay, and intellectual disability. It may also lead to an increased risk of brain tumors.

5. Hyperlysinemia

Description: A disorder caused by defects in lysine degradation, specifically a deficiency in saccharopine dehydrogenase.
Symptoms: Most cases are asymptomatic or mild, but some patients may present with developmental delay, seizures, or muscle weakness.

6. 2-Methyl-3-Hydroxybutyryl-CoA Dehydrogenase Deficiency

Description: A very rare condition involving defects in the breakdown of branched-chain amino acids.
Symptoms: Metabolic acidosis, developmental delay, hypotonia, and neurological deterioration.

7. Pterin-4a-Carbinolamine Dehydratase (PCD) Deficiency

Description: This is an ultra-rare disorder affecting the metabolism of biopterin, a cofactor necessary for neurotransmitter production.
Symptoms: Hyperphenylalaninemia (elevated phenylalanine levels), but often with no or very mild symptoms, unlike phenylketonuria (PKU).

8. Combined D-2-Hydroxyglutaric Aciduria and L-2-Hydroxyglutaric Aciduria

Description: This disorder involves a deficiency in enzymes responsible for the breakdown of D- and L-2-hydroxyglutaric acids, leading to the accumulation of both toxic metabolites.
Symptoms: Progressive neurological deterioration, developmental delay, and seizures.

9. Acyl-CoA Oxidase 2 Deficiency (ACOX2 Deficiency)

Description: This disorder affects the peroxisomal beta-oxidation of bile acids and branched-chain fatty acids due to a deficiency in acyl-CoA oxidase 2.
Symptoms: Liver dysfunction, developmental delay, and hypotonia.

10. 3-Methylglutaconic Aciduria Type IV (Barth Syndrome)

Description: A mitochondrial disorder affecting lipid metabolism, particularly impacting the synthesis of cardiolipin, an important mitochondrial membrane lipid.
Symptoms: Cardiomyopathy, neutropenia, muscle weakness, growth delay, and exercise intolerance. It primarily affects males and is inherited in an X-linked pattern.

11. Beta-Ketothiolase Deficiency (Acetoacetyl-CoA Thiolase Deficiency)

Description: A disorder of ketone body metabolism and isoleucine degradation due to a deficiency in mitochondrial beta-ketothiolase.
Symptoms: Episodes of metabolic ketoacidosis, vomiting, and dehydration, often triggered by illness or fasting.

12. Mevalonate Kinase Deficiency (MKD)

Description: This condition results from defects in the mevalonate pathway, which is important in cholesterol and isoprenoid biosynthesis. There are two forms: a milder form called Hyper-IgD Syndrome (HIDS) and a more severe form known as Mevalonic Aciduria.
Symptoms: Recurrent fever episodes, developmental delay, skin rashes, and dysmorphic features.

13. Dihydropyrimidinase Deficiency

Description: A disorder of pyrimidine metabolism due to a deficiency in dihydropyrimidinase, which results in the accumulation of dihydropyrimidines.
Symptoms: Developmental delays, seizures, and intellectual disability, though symptoms can vary widely.

14. Molybdenum Cofactor Deficiency

Description: A very rare disorder where the body cannot produce a molecule called molybdenum cofactor, which is essential for the activity of several enzymes (such as sulfite oxidase).
Symptoms: Severe neurological deterioration, feeding difficulties, seizures, and brain damage. Symptoms typically appear shortly after birth.

15. Ethylmalonic Encephalopathy

Description: A disorder affecting mitochondrial energy metabolism, caused by a mutation in the ETHE1 gene.
Symptoms: Chronic diarrhea, developmental delays, progressive neurological deterioration, and vascular issues. The hallmark is the presence of ethylmalonic acid in urine.

16. Succinic Semialdehyde Dehydrogenase Deficiency (SSADH Deficiency)

Description: This is a disorder of gamma-aminobutyric acid (GABA) metabolism caused by a deficiency in succinic semialdehyde dehydrogenase.
Symptoms: Developmental delay, ataxia, hypotonia, seizures, and behavioral issues. It can also be associated with sleep disturbances.

17. Glutathione Synthetase Deficiency

Description: A disorder of glutathione metabolism caused by mutations in the GSS gene, leading to a deficiency in the enzyme glutathione synthetase.
Symptoms: Hemolytic anemia, metabolic acidosis, 5-oxoprolinuria, and central nervous system issues such as seizures or developmental delay.

18. Bruck Syndrome

Description: A condition that affects bone formation due to defects in the genes involved in collagen modification. It's a variant of osteogenesis imperfecta with joint contractures.
Symptoms: Frequent bone fractures, joint stiffness (contractures), and skeletal deformities.

19. Fumarase Deficiency

Description: A very rare metabolic disorder caused by mutations in the FH gene, leading to a deficiency in the enzyme fumarase, which is crucial for the citric acid cycle.
Symptoms: Severe developmental delay, microcephaly, hypotonia, seizures, and encephalopathy. It is sometimes called polygamist’s child syndrome due to its higher prevalence in certain isolated populations.

20. Dienoyl-CoA Reductase Deficiency

Description: A disorder of mitochondrial fatty acid beta-oxidation, particularly affecting the breakdown of polyunsaturated fatty acids.
Symptoms: Progressive muscle weakness, hypotonia, developmental delays, and cardiomyopathy.

21. Phosphoribosylpyrophosphate Synthetase Superactivity (PRPS Superactivity)

Description: A rare purine metabolism disorder caused by mutations leading to increased activity of the enzyme PRPP synthetase, resulting in overproduction of purines.
Symptoms: Gout, uric acid kidney stones, hearing loss, and neurological issues.

22. D-Bifunctional Protein Deficiency

Description: A peroxisomal disorder affecting beta-oxidation of very long-chain fatty acids, due to a defect in the enzyme D-bifunctional protein.
Symptoms: Severe neurological impairment, seizures, hypotonia, and developmental delay. Life expectancy is often limited.

23. GABA-Transaminase Deficiency

Description: A disorder of GABA metabolism that results in the accumulation of GABA in the brain due to a deficiency of GABA transaminase.
Symptoms: Severe developmental delay, seizures, and spasticity. This disorder is ultra-rare and leads to profound neurological symptoms.

These ultra-rare metabolic disorders often require highly specialized biochemical and genetic testing for diagnosis. Early detection and intervention can sometimes alleviate or manage symptoms, though many of these conditions remain challenging to treat effectively.

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right.
Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9