Calcium pyrophosphate arthropathy (chondrocalcinosis-2; 118600*)

Increased nucleoside triphosphate pyrophosphohydrolase

Biochemical profile: Calcium pyrophosphate dihydrate crystals in joints

Clinical features: Recurrent episodes of monoarticular or multiarticular arthritis

Treatment: No clear treatment

Lesch-Nyhan syndrome (300322*)

1. Classic form

2. Variant form

Hypoxanthine-guanine phosphoribosyltransferase

Biochemical profile: Hyperuricemia, hyperuricosuria

Clinical features: Orange sandy crystals in diapers, growth failure, uric acid nephropathy and arthropathy, motor delay, hypotonia, self-injurious behavior, spasticity, hyperreflexia, extrapyramidal signs with choreoathetosis, dysarthria, dysphagia, developmental disabilities, megaloblastic anemia

In variant form, no self-injurious behavior

Treatment:

Increased activity of phosphoribosylpyrophosphate synthetase (311850*)

Phosphoribosylpyrophosphate synthetase

Biochemical profile: Hyperuricemia

Clinical features: Megaloblastic bone marrow, ataxia, hypotonia, hypertonia, psychomotor delay, polyneuropathy, cardiomyopathy, heart failure, uric acid nephropathy and arthropathy, diabetes mellitus, intracerebral calcification

Treatment:

Phosphoribosylpyrophosphate synthetase I deficiency (311850*)

Phosphoribosylpyrophosphate synthetase

Biochemical profile: Increased urinary orotate, hypouricemia

Clinical features: Developmental disabilities, seizures with hypsarrhythmia, megaloblastic bone marrow

Treatment: Adrenocorticotropic hormone

Hereditary xanthinuria

Biochemical profile: Xanthinuria, hypouricemia, hypouricosuria

Clinical features: Xanthine stones, nephropathy, myopathy

Treatment: High fluid intake; low-purine diet

Type I (278300*)

Xanthine dehydrogenase

Type II (603592*)

Xanthine dehydrogenase and aldehyde oxidase

Adenine phosphoribosyltransferase deficiency (102600*)

Adenine phosphoribosyltransferase

Biochemical profile: Urinary 2,8-dihydroxyadenine

Clinical features: Urolithiasis, nephropathy, round yellow-brown urine crystals

Treatment: High fluid intake, low-purine diet, avoidance of dietary alkalis, renal transplantation

Type I

No enzyme activity

Type II

Residual enzyme activity

(102700*)

Adenosine deaminase

Biochemical profile: Elevated serum adenosine and 2′-deoxyadenosine

Clinical features: Growth failure, skeletal changes, recurrent infections, severe combined immunodeficiency, B-cell lymphoma, hemolytic anemia, idiopathic thrombocytopenia, hepatosplenomegaly, mesangial sclerosis

Treatment: Supportive care, enzyme replacement, bone marrow or stem cell transplantation, experimental gene therapy

Increased adenosine deaminase (102730*)

Adenosine deaminase

Biochemical profile: Mild hyperuricemia

Clinical features: Hemolytic anemia with anisopoikilocytosis and stomatocytosis

Treatment: Deoxycoformycin

Purine nucleoside phosphorylase deficiency (164050*)

Purine nucleoside phosphorylase

Biochemical profile: Hypouricemia; hypouricosuria; high serum inosine and guanine; high urinary inosine, 2′-deoxyinosine, and 2′-deodyguanosine

Clinical features: Growth failure, cellular immunodeficiency, recurrent infections, hepatosplenomegaly, cerebral vasculitis, spastic diplegia, tetraparesis, ataxia, tremors, hypotonia, hypertonia, developmental disabilities, autoimmune hemolytic anemia, idiopathic thrombocytopenia, lymphoma, lymphosarcoma

Treatment: Supportive care, stem cell transplantation

Myoadenylate deaminase deficiency (adenosine monophosphate deaminase I; 102770*)

Myoadenylate deaminase

Biochemical profile: No specific change

Clinical features: Neonatal weakness and hypotonia; exercise-induced weakness or cramping; after exercise, decreased purine release and low increase in serum ammonia (relative to lactate)

Treatment: Ribose or xylitol

Adenylate kinase deficiency (103000*)

Adenylate kinase

Biochemical profile: No specific change

Clinical features: Hemolytic anemia

Treatment: Supportive care

Adenylosuccinase deficiency (103050*)

1. Type I (severe form)

2. Type II (mild form)

Adenylosuccinate lyase

Biochemical profile: Elevated succinyladenosine and succinylaminoimidazole carboxamide ribotides in body fluids

Clinical features: Autism, severe psychomotor delay, seizures, growth delay, muscle wasting

Treatment: Supportive care, adenine, and ribose