Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. It is a classical type of organic acidemia. The result of this condition is the inability to properly digest specific fats and proteins, which in turn leads to a buildup of a toxic level of methylmalonic acid in the blood.
CADASIL or CADASIL syndrome, involving cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is the most common form of hereditary stroke disorder, and is thought to be caused by mutations of the Notch 3 gene on chromosome 19. The disease belongs to a family of disorders called the leukodystrophies. The most common clinical manifestations are migraine headaches and transient ischemic attacks or strokes, which usually occur between 40 and 50 years of age, although MRI is able to detect signs of the disease years prior to clinical manifestation of disease.
Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine and earwax, particularly prior to diagnosis and during times of acute illness. It was described by John Menkes in the 1950s.
Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body. Nonsyndromic deafness constitutes 75% of all hearing loss cases, and an estimated 100 genes are thought to be linked to this condition. About 80% are linked to autosomal recessive inheritance, 15% to autosomal dominant inheritance, 1-3% through the X chromosome, and 0.5-1% are associated with mitochondrial inheritance.
Myoclonic epilepsy refers to a family of epilepsies that present with myoclonus. When myoclonic jerks are occasionally associated with abnormal brain wave activity, it can be categorized as myoclonic seizure. If the abnormal brain wave activity is persistent and results from ongoing seizures, then a diagnosis of myoclonic epilepsy may be considered.
Glycine encephalopathy is a rare autosomal recessive disorder of glycine metabolism. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. The disease is caused by defects in the glycine cleavage system, an enzyme responsible for glycine catabolism. There are several forms of the disease, with varying severity of symptoms and time of onset. The symptoms are exclusively neurological in nature, and clinically this disorder is characterized by abnormally high levels of the amino acid glycine in bodily fluids and tissues, especially the cerebrospinal fluid.
Autosomal recessive multiple epiphyseal dysplasia (ARMED), also called epiphyseal dysplasia, multiple, 4 (EDM4), multiple epiphyseal dysplasia with clubfoot or –with bilayered patellae, is an autosomal recessive congenital disorder affecting cartilage and bone development. The disorder has relatively mild signs and symptoms, including joint pain, scoliosis, and malformations of the hands, feet, and knees.
Pallister–Hall syndrome (PHS) is a rare genetic disorder that affects various body systems. The main features are a non-cancerous mass on the hypothalamus and extra digits (polydactylism). The prevalence of Pallister-Hall Syndrome is unknown; about 100 cases have been reported in publication.
Cutis laxa or pachydermatocele is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds.
Congenital muscular dystrophies are autosomal recessively-inherited muscle diseases. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges from myopathic to overtly dystrophic due to the age at which the biopsy takes place.
Lysyl hydroxylases are alpha-ketoglutarate-dependent hydroxylases enzymes that catalyze the hydroxylation of lysine to hydroxylysine. Lysyl hydroxylases require iron and vitamin C as cofactors for their oxidation activity. It takes place following collagen synthesis in the cisternae (lumen) of the rough endoplasmic reticulum (ER). There are three lysyl hydroxylases (LH1-3) encoded in the human genome, namely: PLOD1, PLOD2 and PLOD3. From PLOD2 two splice variant can be expressed, where LH2b differs from LH2a by incorporating the small exon 13A. LH1 and LH3 hydroxylate lysyl residues in the collagen triple helix, whereas LH2b hydroxylates lysyl residues in the telopeptides of collagen. In addition to its hydroxylation activity, LH3 has glycosylation activity that produces either monosaccharide (Gal) or disaccharide (Glc-Gal) attached to collagen hydroxylysines.
Amelia is the birth defect of lacking one or more limbs. The term may be modified to indicate the number of legs or arms missing at birth, such as tetra-amelia for the absence of all four limbs. The term is from Greek ἀ- 'lack of' plus μέλος 'limb'.
Juvenile polyposis syndrome is an autosomal dominant genetic condition characterized by the appearance of multiple juvenile polyps in the gastrointestinal tract. Polyps are abnormal growths arising from a mucous membrane. These usually begin appearing before age 20, but the term juvenile refers to the type of polyp, not to the age of the affected person. While the majority of the polyps found in juvenile polyposis syndrome are non-neoplastic, hamartomatous, self-limiting and benign, there is an increased risk of adenocarcinoma.
Ganglioside-induced differentiation-associated protein 1 is a type of protein that in humans is encoded by the GDAP1 gene.
X-linked spinal muscular atrophy type 2, also known as arthrogryposis multiplex congenita X-linked type 1 (AMCX1), is a rare neurological disorder involving death of motor neurons in the anterior horn of spinal cord resulting in generalised muscle wasting (atrophy). The disease is caused by a mutation in UBA1 gene and is passed in an X-linked recessive manner by carrier mothers to affected sons.
Neurodegeneration with brain iron accumulation is a heterogenous group of inherited neurodegenerative diseases, still under research, in which iron accumulates in the basal ganglia, either resulting in progressive dystonia, parkinsonism, spasticity, optic atrophy, retinal degeneration, neuropsychiatric, or diverse neurologic abnormalities. Some of the NBIA disorders have also been associated with several genes in synapse and lipid metabolism related pathways. NBIA is not one disease but an entire group of disorders, characterized by an accumulation of brain iron, sometimes in the presence of axonal spheroids in the central nervous system.
Genitopatellar syndrome is a rare disorder consisting of congenital flexion contractures of the lower extremities, abnormal or missing patellae, and urogenital anomalies. Additional symptoms include microcephaly, severe psychomotor disability. In 2012, it was shown that mutations in the gene KAT6B cause the syndrome. Genitopatellar syndrome (GTPTS) can be caused by heterozygous mutation in the KAT6B gene on chromosome 10q22. The Say-Barber-Biesecker variant of Ohdo syndrome, which has many overlapping features with GTPTS, can also be caused by heterozygous mutation in the KAT6B gene.
Microlissencephaly (MLIS) is a rare congenital brain disorder that combines severe microcephaly with lissencephaly. Microlissencephaly is a heterogeneous disorder, i.e. it has many different causes and a variable clinical course. Microlissencephaly is a malformation of cortical development (MCD) that occurs due to failure of neuronal migration between the third and fifth month of gestation as well as stem cell population abnormalities. Numerous genes have been found to be associated with microlissencephaly, however, the pathophysiology is still not completely understood.
MUTYH-associated polyposis is an autosomal recessive polyposis syndrome. The disorder is caused by mutations in both alleles of the DNA repair gene, MUTYH. The MUTYH gene encodes a base excision repair protein, which corrects oxidative damage to DNA. Affected individuals have an increased risk of colorectal cancer, precancerous colon polyps (adenomas) and an increased risk of several additional cancers. About 1–2 percent of the population possess a mutated copy of the MUTYH gene, and less than 1 percent of people have the MUTYH-associated polyposis syndrome. The presence of 10 or more colon adenomas should prompt consideration of MUTYH-associated polyposis, familial adenomatous polyposis and similar syndromes.
Nasu–Hakola disease also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is a rare disease characterised by early-onset dementia and multifocal bone cysts. It is caused by autosomal recessive loss of function mutations in either the TREM2 or TYROBP gene that are found most frequently in the Finnish and Japanese populations.
