Inherited and other metabolic disorders

Hurler syndrome

Hurler syndrome, also called Hurler's disease, is the most severe form of mucopolysaccharidosis type I, an inherited disorder causing developmental decline and death in childhood if untreated.

Hyaluronidase deficiency (MPS IX, Natowicz syndrome) is an ultra-rare autosomal recessive lysosomal storage disease caused by HYAL1 deficiency, with hyaluronan storage, periarticular masses, and joint disease; only four patients reported.

Hydroxykynureninuria

Hydroxykynureninuria, also known as xanthurenic aciduria or kynureninase deficiency, is a very rare inherited disorder of tryptophan metabolism with large urinary losses of xanthurenic acid, kynurenine, and 3-hydroxykynurenine.

Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency

Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (CA5AD, CA-VA deficiency) is a rare autosomal recessive CA5A disorder causing neonatal hyperammonemia, lactic acidosis, and ketonuria, treated with carglumic acid.

Hypercholesterolaemia

Hypercholesterolemia, also spelled hypercholesterolaemia, is the condition of abnormally high cholesterol in the blood and the most common form of dyslipidaemia, a major modifiable risk factor for heart attack and stroke.

Hyperinsulinism-hyperammonemia syndrome

Hyperinsulinism-hyperammonemia (HI/HA, GDH-HI) syndrome: a dominant GLUD1 gain-of-function disorder causing leucine-sensitive hypoglycemia, chronic hyperammonemia, epilepsy, and diazoxide-responsive congenital hyperinsulinism.

Hyperlipidemia

Hyperlipidemia (hypercholesterolemia, lipid disorder) is abnormally high blood lipids or lipoproteins. High LDL and triglycerides drive atherosclerosis; detected by lipid profile, treated with statins, ezetimibe, PCSK9 inhibitors.

Hypermethioninemia due to glycine N-methyltransferase deficiency

Hypermethioninemia due to glycine N-methyltransferase deficiency (GNMT deficiency, OMIM 606664) is a rare autosomal recessive disorder causing permanent marked hypermethioninemia with high AdoMet, normal AdoHcy, and mild liver enzyme elevations.

Hyperphenylalaninemia due to tetrahydrobiopterin deficiency

Hyperphenylalaninemia due to tetrahydrobiopterin deficiency (BH4 deficiency, atypical/malignant PKU): rare autosomal recessive disorders of GCH1, PTS, QDPR, or PCBD1 causing elevated phenylalanine plus dopamine and serotonin deficiency, treated with BH4, L-dopa, and 5-hydroxytryptophan.

Hyperplasia

Hyperplasia is an increase in the number of cells in an organ or tissue, making it larger; the cells look normal and are not cancer, though some forms may become cancer.

Hyperprolinemia type 1

Hyperprolinemia type 1 (HPI, proline oxidase deficiency, OMIM 239500) is a rare autosomal recessive PRODH disorder at 22q11.21 causing high blood proline without urinary P5C; often asymptomatic, occasionally seizures, schizophrenia, or nephropathy.

Hyperprolinemia type 2

Hyperprolinemia type 2 (HPII, ALDH4A1 hyperprolinemia, delta-1-pyrroline-5-carboxylate dehydrogenase deficiency) is an autosomal recessive proline metabolism disorder causing proline 10-15x normal with elevated P5C, sometimes seizures and intellectual disability, often benign.

Hypertriglyceridemia

Hypertriglyceridemia (HTG): fasting triglycerides above 150 mg/dL. Classified mild to very severe; causes ASCVD risk and pancreatitis at ≥500–1000 mg/dL. Treated with lifestyle, fibrates, omega-3s, statins, and new APOC3 agents like olezarsen.

Hypertryptophanemia

Hypertryptophanemia, also called familial hypertryptophanemia (OMIM 600627), is a rare autosomal recessive inborn error of tryptophan metabolism caused by TDO2 deficiency, producing congenital hypertryptophanemia, hyperserotonemia, and tryptophanuria, usually without symptoms.

Hyperuricemia

Hyperuricemia is abnormally high blood uric acid (serum urate above 6.8 mg/dL), caused by overproduction or underexcretion of urate after humans lost uricase. It causes gout and kidney stones; treated with allopurinol, febuxostat, uricosurics, or uricases.

Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome

HUPRA syndrome (hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome), also called HUPRAS, is an ultra-rare autosomal recessive mitochondrial disease caused by SARS2 mutations, presenting in infancy with renal failure, metabolic alkalosis, and pulmonary hypertension.

Hypolipoproteinaemia

Hypolipoproteinaemia (ICD-11 5C81), abnormally low plasma lipoproteins; primary forms include abetalipoproteinemia (MTTP), familial hypobetalipoproteinemia (APOB), chylomicron retention disease (SAR1B), PCSK9 and ANGPTL3 defects; also secondary causes.

Hypotonia-cystinuria syndrome

Hypotonia-cystinuria syndrome (HCS, OMIM 606407) is a rare autosomal recessive 2p21 contiguous gene deletion of SLC3A1 and PREPL causing neonatal hypotonia, cystinuria type 1, kidney stones, growth hormone deficiency, and hyperphagia in late childhood.

Hypoxanthine guanine phosphoribosyltransferase partial deficiency

Hypoxanthine guanine phosphoribosyltransferase partial deficiency (Kelley-Seegmiller syndrome, Lesch-Nyhan variant, OMIM 300323) is an X-linked HPRT1 disorder causing uric acid overproduction, gout, and variable neurological signs without self-injury.

Inborn errors of carbohydrate metabolism

Inborn errors of carbohydrate metabolism are inherited enzyme defects disrupting galactose, glycogen, fructose, and pyruvate metabolism, including galactosemia, von Gierke disease, and hereditary fructose intolerance, diagnosed by enzymatic and molecular testing and treated mainly by diet.

Inborn errors of energy metabolism

Inborn errors of energy metabolism (ICD-11 5C53) are inherited defects impairing cellular energy production or use, covering fatty acid oxidation, mitochondrial, glycogen, and creatine disorders, presenting with hypoglycemia, lactic acidosis, hypotonia, and myopathy.

Inborn errors of lipid metabolism

Inborn errors of lipid metabolism (ICD-11 5C52) are heritable genetic disorders of lipid transport, oxidation, synthesis, and storage, including fatty acid oxidation defects, complex lipid biosynthesis disorders, sphingolipidoses, and lipoprotein disorders.

Infantile neurovisceral acid sphingomyelinase deficiency

Infantile neurovisceral acid sphingomyelinase deficiency (Niemann-Pick disease type A, NPD-A): severe autosomal recessive SMPD1 lysosomal storage disease of infancy with hepatosplenomegaly, neurodegeneration, and death by about age 3.

Iron overload diseases

Iron overload diseases are conditions in which excess iron accumulates in body tissues, damaging the liver, pancreas, and heart, usually through hereditary hemochromatosis or repeated transfusions.

Isolated glycerol kinase deficiency

Isolated glycerol kinase deficiency (GKD, hyperglycerolemia, OMIM 307030) is a rare X-linked recessive GK-gene disorder causing hyperglycerolemia, glyceroluria, and pseudohypertriglyceridemia, from asymptomatic adults to childhood metabolic crises.

Isolated sedoheptulokinase deficiency

Isolated sedoheptulokinase deficiency (SHPK deficiency, OMIM 617213) is an autosomal recessive pentose phosphate pathway disorder causing elevated urinary sedoheptulose and erythritol; its clinical relevance is unclear, with only two isolated cases reported.

Keppen-Lubinsky syndrome

Keppen-Lubinsky syndrome (KPLBS, OMIM 614098), a rare autosomal dominant KCNJ6/GIRK2 channelopathy causing generalized lipodystrophy, progeroid features, severe intellectual disability, and facial dysmorphism; de novo selectivity-filter mutations, fewer than 1 in 1,000,000 prevalence.

L-Arginine:glycine amidinotransferase deficiency

AGAT deficiency (GATM, OMIM 612718), an ultrarare autosomal recessive creatine biosynthesis disorder with under 20 reported cases, causing developmental delay, intellectual disability, myopathy, low guanidinoacetate, and treatable with creatine monohydrate.

L-ferritin deficiency

L-ferritin deficiency (ORPHA:440731, OMIM 615604) is a rare FTL-gene iron-metabolism disorder with undetectable serum L-ferritin but normal iron parameters, causing seizures, atypical restless legs, and hair loss.