Pancreatic agenesis 1

A disease characterized by isolated hypoplasia or agenesis of the pancreas, pancreatic beta-cell failure resulting in neonatal insulin-dependent diabetes mellitus, and exocrine pancreatic insufficiency.

Adenylosuccinase deficiency

An autosomal recessive disorder characterized by the accumulation in the body fluids of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado). Most children display marked psychomotor delay, often accompanied by epilepsy or autistic features, or both, although some patients may be less profoundly retarded. Occasionally, growth retardation and muscular wasting are also present.

Myopathy due to myoadenylate deaminase deficiency

A metabolic disorder resulting in exercise-related myopathy. It is characterized by exercise-induced muscle aches, cramps, and early fatigue.

Glycogen storage disease 12

A metabolic disorder associated with increased hepatic glycogen and hemolytic anemia. It may lead to myopathy with exercise intolerance and rhabdomyolysis.

P5N deficiency

Autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties.

Mitochondrial DNA depletion syndrome 2

A disorder due to mitochondrial dysfunction characterized by childhood onset of muscle weakness associated with depletion of mtDNA in skeletal muscle. There is wide clinical variability; some patients have onset in infancy and show a rapidly progressive course with early death due to respiratory failure, whereas others have later onset of a slowly progressive myopathy.

Maturity-onset diabetes of the young 14

A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.

Combined oxidative phosphorylation deficiency 24

An autosomal recessive mitochondrial disorder with wide phenotypic variability. Some patients have a milder form affecting only skeletal muscle, whereas others may have a more severe disorder, reminiscent of Alpers syndrome. Alpers syndrome is a progressive neurodegenerative disorder that presents in infancy or early childhood and is characterized by diffuse degeneration of cerebral gray matter.

Beta-ureidopropionase deficiency

An inborn error of metabolism due to a defect in pyrimidine degradation. It is characterized by muscular hypotonia, dystonic movements, scoliosis, microcephaly and severe developmental delay. Patients show strongly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in plasma, cerebrospinal fluid and urine.

Mitochondrial DNA depletion syndrome 8A

A disorder due to mitochondrial dysfunction characterized by various combinations of neonatal hypotonia, neurological deterioration, respiratory distress, lactic acidosis, and renal tubulopathy.

Adenosine monophosphate deaminase deficiency erythrocyte type

A metabolic disorder due to lack of activity of the erythrocyte isoform of AMP deaminase. It is a clinically asymptomatic condition characterized by a 50% increase in steady-state levels of ATP in affected cells. Individuals with complete deficiency of erythrocyte AMP deaminase are healthy and have no hematologic disorders.

Leucine-induced hypoglycemia

Rare cause of hypoglycemia and is described as a condition in which symptomatic hypoglycemia is provoked by high protein feedings. Hypoglycemia is also elicited by administration of oral or intravenous infusions of a single amino acid, leucine.

Anemia, congenital, non-spherocytic hemolytic, 5

An autosomal recessive disorder characterized by hemolytic anemia as the predominant clinical feature, and decreased red cell hexokinase activity.

Anemia, congenital, non-spherocytic hemolytic, 4

An autosomal recessive form of anemia in which there is no abnormal hemoglobin or spherocytosis. It is caused by glucose phosphate isomerase deficiency.

Pyruvate kinase hyperactivity

Autosomal dominant phenotype characterized by increase of red blood cell ATP.

AICA-ribosuria due to ATIC deficiency

A neurologically devastating inborn error of purine biosynthesis. Patients excrete massive amounts of AICA-riboside in the urine and accumulate AICA-ribotide and its derivatives in erythrocytes and fibroblasts. Clinical features include profound intellectual disability, epilepsy, dysmorphic features and congenital blindness. AICAR inheritance is autosomal recessive.

Dihydropyrimidinase deficiency

An autosomal recessive disorder of pyrimidine metabolism characterized by dihydropyrimidinuria. It is associated with a variable clinical phenotype characterized by epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy. Most patients are, however, asymptomatic.

X-linked dyserythropoietic anemia and thrombocytopenia

Disorder characterized by erythrocytes with abnormal size and shape, and paucity of platelets in peripheral blood. The bone marrow contains abundant and abnormally small megakaryocytes.

Adenine phosphoribosyltransferase deficiency

An enzymatic deficiency that can lead to urolithiasis and renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones.

Glycogen storage disease 7

A metabolic disorder characterized by exercise intolerance with associated nausea and vomiting, muscle cramping, exertional myopathy and compensated hemolysis. Short bursts of intense activity are particularly difficult. Severe muscle cramps and myoglobinuria develop after vigorous exercise.

Dihydropyrimidine dehydrogenase deficiency

A metabolic disorder with large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and intellectual disability. It is characterized by persistent urinary excretion of excessive amounts of uracil, thymine and 5-hydroxymethyluracil. Patients suffering from this disease show a severe reaction to the anticancer drug 5-fluorouracil.

Phosphoglycerate kinase 1 deficiency

A condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations, and some affected individuals develop parkinsonian symptoms.

Renal cysts and diabetes syndrome

An autosomal dominant disorder comprising non-diabetic renal disease resulting from abnormal renal development, and diabetes, which in some cases occurs earlier than age 25 years and is thus consistent with a diagnosis of maturity-onset diabetes of the young (MODY5). The renal disease is highly variable and includes renal cysts, glomerular tufts, aberrant nephrogenesis, primitive tubules, irregular collecting systems, oligomeganephronia, enlarged renal pelves, abnormal calyces, small kidney, single kidney, horseshoe kidney, and hyperuricemic nephropathy. Affected individuals may also have abnormalities of the genital tract.

Xanthinuria 2

A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. In addition, XAN2 patients cannot metabolize allopurinol into oxypurinol due to dual deficiency of xanthine dehydrogenase and aldehyde oxidase.

Tubulointerstitial kidney disease, autosomal dominant 1

A form of autosomal dominant tubulointerstitial kidney disease, a genetically heterogeneous disorder characterized by slowly progressive loss of kidney function, bland urinary sediment, hyperuricemia, absent or mildly increased albuminuria, lack of severe hypertension during the early stages, and normal or small kidneys on ultrasound. Renal histology shows variable abnormalities including interstitial fibrosis with tubular atrophy, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. There is significant variability, as well as incomplete penetrance.

Lesch-Nyhan syndrome

Characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, intellectual disability, and compulsive self-mutilation.

Inosine triphosphate pyrophosphohydrolase deficiency

A common inherited condition characterized by the abnormal accumulation of inosine triphosphate in erythrocytes. It might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs.

Mitochondrial DNA depletion syndrome 20, MNGIE type

An autosomal recessive mitochondrial disorder characterized by severe gut dysmotility, muscle weakness and atrophy, neurological abnormalities including epilepsy, migraine, stroke-like episodes, learning difficulties or cognitive decline, and neurogenic bladder. Brain imaging usually shows diffuse leukoencephalopathy and may show cerebellar atrophy. Disease onset can range from infancy to the teenage years.

Glycogen storage disease 13

A metabolic disorder that results in exercise-induced myalgias, generalized muscle weakness and fatigability. It is characterized by increased serum creatine kinase and decreased enolase 3 activity. Dramatically reduced protein levels with focal sarcoplasmic accumulation of glycogen-beta particles are detected on ultrastructural analysis.

Glycogen storage disease 10

A metabolic disorder characterized by myoglobinuria, increased serum creatine kinase levels, decreased phosphoglycerate mutase activity, myalgia, muscle pain, muscle cramps, exercise intolerance.

D-lactic aciduria with gout

An autosomal recessive metabolic disorder characterized by D-lactic aciduria in the presence of normal plasma lactic acid.

Maturity-onset diabetes of the young 6

A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.

Hepatic adenomas familial

Rare benign liver tumors of presumable epithelial origin that develop in an otherwise normal liver. Hepatic adenomas may be single or multiple. They consist of sheets of well-differentiated hepatocytes that contain fat and glycogen and can produce bile. Bile ducts or portal areas are absent. Kupffer cells, if present, are reduced in number and are non-functional. Conditions associated with adenomas are insulin-dependent diabetes mellitus and glycogen storage diseases (types 1 and 3).

Glycogen storage disease 11

A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 1

A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.

Mitochondrial DNA depletion syndrome 3

A disorder due to mitochondrial dysfunction characterized by onset in infancy of progressive liver failure, hypoglycemia, increased lactate in body fluids, and neurologic abnormalities including hypotonia, encephalopathy, peripheral neuropathy. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes and mtDNA depletion.

Mitochondrial DNA depletion syndrome 1, MNGIE type

A multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, cachexia, peripheral neuropathy, and myopathy.

Triosephosphate isomerase deficiency

An autosomal recessive multisystem disorder characterized by congenital hemolytic anemia, progressive neuromuscular dysfunction, susceptibility to bacterial infection, and cardiomyopathy.

Xanthinuria 1

A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. XAN1 is due to isolated xanthine dehydrogenase deficiency. Patients can metabolize allopurinol.

Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-negative due to adenosine deaminase deficiency

An autosomal recessive disorder accounting for about 50% of non-X-linked SCIDs. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. ADA deficiency has been diagnosed in chronically ill teenagers and adults (late or adult onset). Population and newborn screening programs have also identified several healthy individuals with normal immunity who have partial ADA deficiency.

Orotic aciduria 1

A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and intellectual disability. A minority of cases have additional features, particularly congenital malformations and immune deficiencies.

Maturity-onset diabetes of the young 11

A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.

Hyperproinsulinemia

An autosomal dominant condition characterized by elevated levels of serum proinsulin-like material.

Lactate dehydrogenase B deficiency

A condition with no deleterious effects on health. LDHBD is of interest to laboratory medicine mainly because it can cause misdiagnosis in those disorders in which elevation of serum LDH is expected.

Maturity-onset diabetes of the young 8 with exocrine dysfunction

An autosomal dominant form of diabetes characterized by a primary defect in insulin secretion, exocrine pancreatic dysfunction, altered pancreatic morphology, recurrent abdominal pain, and fecal elastase deficiency. Disease onset is at less than 25 years of age.

Maturity-onset diabetes of the young 7

A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.

Type 2 diabetes mellitus

A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.

Maturity-onset diabetes of the young 1

A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.

Hyperinsulinemic hypoglycemia, familial, 2

A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF2 is a common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF2 inheritance can be autosomal dominant or autosomal recessive.